A copy number variation that results in reduced GENE DOSAGE due to any loss-of-function mutation. The loss of heterozygosity is associated with abnormal phenotypes or diseased states because the remaining gene is insufficient.
Processes occurring in various organisms by which new genes are copied. Gene duplication may result in a MULTIGENE FAMILY; supergenes or PSEUDOGENES.
Genes that influence the PHENOTYPE only in the homozygous state.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are SACCHAROMYCES CEREVISIAE; therapeutic dried yeast is YEAST, DRIED.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The complete gene complement contained in a set of chromosomes in a fungus.
A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques.
The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulchi. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
The measurement of an organ in volume, mass, or heaviness.
A species of nematode that is widely used in biological, biochemical, and genetic studies.
Proteins from the nematode species CAENORHABDITIS ELEGANS. The proteins from this species are the subject of scientific interest in the area of multicellular organism MORPHOGENESIS.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
A POU domain factor that activates GENETIC TRANSCRIPTION of GENES encoding NEUROFILAMENT PROTEINS; alpha internexin; SYNAPTOSOMAL-ASSOCIATED PROTEIN 25; and BCL-2 PROTO-ONCOGENE PROTEINS.
A family of mammalian POU domain factors that are expressed predominately in NEURONS.
A family of transcription factors characterized by the presence of a bipartite DNA-binding domain known as the POU domain. The POU domain contains two subdomains, a POU-specific domain and a POU-homeodomain. The POU domain was originally identified as a region of approximately 150 amino acids shared between the Pit-1, Oct-1, Oct-2, and Unc-86 transcription factors.
An octamer transcription factor that plays an important role in the MYELIN SHEATH development by SCHWANN CELLS.
A POU domain factor that represses GENETIC TRANSCRIPTION of GENES encoding NEUROFILAMENT PROTEINS, alpha internexin, and SYNAPTOSOMAL-ASSOCIATED PROTEIN 25.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Genetic mechanisms that allow GENES to be expressed at a similar level irrespective of their GENE DOSAGE. This term is usually used in discussing genes that lie on the SEX CHROMOSOMES. Because the sex chromosomes are only partially homologous, there is a different copy number, i.e., dosage, of these genes in males vs. females. In DROSOPHILA, dosage compensation is accomplished by hypertranscription of genes located on the X CHROMOSOME. In mammals, dosage compensation of X chromosome genes is accomplished by random X CHROMOSOME INACTIVATION of one of the two X chromosomes in the female.
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)
Molecule produced in plant leaves that acts like a hormone by inducing flowering in the shoot apical meristem of buds and growing tips.
A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)
An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.
Individual's rights to obtain and use information collected or generated by others.
OXIDOREDUCTASES which mediate vitamin K metabolism by converting inactive vitamin K 2,3-epoxide to active vitamin K.
A quantitative measure of the frequency on average with which articles in a journal have been cited in a given period of time.
The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)
A multisubunit polycomb protein complex with affinity for CHROMATIN that contains methylated HISTONE H3. It contains an E3 ubiquitin ligase activity that is specific for HISTONE H2A and works in conjunction with POLYCOMB REPRESSIVE COMPLEX 2 to effect EPIGENETIC REPRESSION.
A species of fruit fly much used in genetics because of the large size of its chromosomes.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A family of proteins that play a role in CHROMATIN REMODELING. They are best known for silencing HOX GENES and the regulation of EPIGENETIC PROCESSES.
A multisubunit polycomb protein complex that catalyzes the METHYLATION of chromosomal HISTONE H3. It works in conjunction with POLYCOMB REPRESSIVE COMPLEX 1 to effect EPIGENETIC REPRESSION.
Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
The human female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in humans.
A dosage compensation process occurring at an early embryonic stage in mammalian development whereby, at random, one X CHROMOSOME of the pair is repressed in the somatic cells of females.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Any method used for determining the location of and relative distances between genes on a chromosome.
The homologous chromosomes that are dissimilar in the heterogametic sex. There are the X CHROMOSOME, the Y CHROMOSOME, and the W, Z chromosomes (in animals in which the female is the heterogametic sex (the silkworm moth Bombyx mori, for example)). In such cases the W chromosome is the female-determining and the male is ZZ. (From King & Stansfield, A Dictionary of Genetics, 4th ed)

Apontic binds the translational repressor Bruno and is implicated in regulation of oskar mRNA translation. (1/5148)

The product of the oskar gene directs posterior patterning in the Drosophila oocyte, where it must be deployed specifically at the posterior pole. Proper expression relies on the coordinated localization and translational control of the oskar mRNA. Translational repression prior to localization of the transcript is mediated, in part, by the Bruno protein, which binds to discrete sites in the 3' untranslated region of the oskar mRNA. To begin to understand how Bruno acts in translational repression, we performed a yeast two-hybrid screen to identify Bruno-interacting proteins. One interactor, described here, is the product of the apontic gene. Coimmunoprecipitation experiments lend biochemical support to the idea that Bruno and Apontic proteins physically interact in Drosophila. Genetic experiments using mutants defective in apontic and bruno reveal a functional interaction between these genes. Given this interaction, Apontic is likely to act together with Bruno in translational repression of oskar mRNA. Interestingly, Apontic, like Bruno, is an RNA-binding protein and specifically binds certain regions of the oskar mRNA 3' untranslated region.  (+info)

DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model. (2/5148)

Myotonic dystrophy (DM) is the most common form of muscular dystrophy and is caused by expansion of a CTG trinucleotide repeat on human chromosome 19. Patients with DM develop atrioventricular conduction disturbances, the principal cardiac manifestation of this disease. The etiology of the pathophysiological changes observed in DM has yet to be resolved. Haploinsufficiency of myotonic dystrophy protein kinase (DMPK), DM locus-associated homeodomain protein (DMAHP) and/or titration of RNA-binding proteins by expanded CUG sequences have been hypothesized to underlie the multi-system defects observed in DM. Using an in vivo murine electrophysiology study, we show that cardiac conduction is exquisitely sensitive to DMPK gene dosage. DMPK-/- mice develop cardiac conduction defects which include first-, second-, and third-degree atrioventricular (A-V) block. Our results demonstrate that the A-V node and the His-Purkinje regions of the conduction system are specifically compromised by DMPK loss. Importantly, DMPK+/- mice develop first-degree heart block, a conduction defect strikingly similar to that observed in DM patients. These results demonstrate that DMPK dosage is a critical element modulating cardiac conduction integrity and conclusively link haploinsufficiency of DMPK with cardiac disease in myotonic dystrophy.  (+info)

Down-regulation of RpS21, a putative translation initiation factor interacting with P40, produces viable minute imagos and larval lethality with overgrown hematopoietic organs and imaginal discs. (3/5148)

Down-regulation of the Drosophila ribosomal protein S21 gene (rpS21) causes a dominant weak Minute phenotype and recessively produces massive hyperplasia of the hematopoietic organs and moderate overgrowth of the imaginal discs during larval development. Here, we show that the S21 protein (RpS21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein. RpS21 can interact strongly with P40, a ribosomal peripheral protein encoded by the stubarista (sta) gene. Genetic studies reveal that P40 underexpression drastically enhances imaginal disc overgrowth in rpS21-deficient larvae, whereas viable combinations between rpS21 and sta affect the morphology of bristles, antennae, and aristae. These data demonstrate a strong interaction between components of the translation machinery and showed that their underexpression impairs the control of cell proliferation in both hematopoietic organs and imaginal discs.  (+info)

Cloning, molecular analysis and differential cell localisation of the p36 RACK analogue antigen from the parasite protozoon Crithidia fasciculata. (4/5148)

The family of the RACK molecules (receptors for activated C kinases) are present in all the species studied so far. In the genus Leishmania, these molecules also induce a strong immune reaction against the infection. We have cloned and characterised the gene that encodes the RACK analogue from the parasite trypanosomatid Crithidia fasciculata (CACK). The molecule seems to be encoded by two genes. The sequence analysis of the cloned open reading frame indicates the existence of a high degree of conservation not only with other members of the Trypanosomatidae but also with mammalians. The study of the protein kinase C phosphorylation sites shows the presence of three of them, shared with the mammalian species, additional to those present in the other protozoa suggesting a certain phylogenetic distance between the protozoon Crithidia fasciculata and the rest of the Trypanosomatidae. The CACK-encoded polypeptide shows an additional sequence of four amino acids at the carboxy-terminal end, which produces a different folding of the fragment with the presence of an alpha-helix instead of the beta-sheet usual in all the other species studied. A similar result is elicited at the amino-terminal end by the change of three amino acid residues. The immunolocalisation experiments show that the CACK displays a pattern with a distribution mainly at the plasma membrane, different from that of the related Leishmania species used as control, that displays a distribution close to the nucleus. Altogether, the data suggest that the existence of the structural differences found may have functional consequences.  (+info)

The origin and evolution of green algal and plant actins. (5/5148)

The Viridiplantae are subdivided into two groups: the Chlorophyta, which includes the Chlorophyceae, Trebouxiophyceae, Ulvophyceae, and Prasinophyceae; and the Streptophyta, which includes the Charophyceae and all land plants. Within the Streptophyta, the actin genes of the angiosperms diverge nearly simultaneously from each other before the separation of monocots and dicots. Previous evolutionary analyses have provided limited insights into the gene duplications that have produced these complex gene families. We address the origin and diversification of land plant actin genes by studying the phylogeny of actins within the green algae, ferns, and fern allies. Partial genomic sequences or cDNAs encoding actin were characterized from Cosmarium botrytis (Zygnematales), Selaginella apoda (Selaginellales), Anemia phyllitidis (Polypodiales), and Psilotum triquetrum (Psilotales). Selaginella contains at least two actin genes. One sequence (Ac2) diverges within a group of fern sequences that also includes the Psilotum Ac1 actin gene and one gymnosperm sequence (Cycas revoluta Cyc3). This clade is positioned outside of the angiosperm actin gene radiation. The second Selaginella sequence (Ac1) is the sister to all remaining land plant actin sequences, although the internal branches in this portion of the tree are very short. Use of complete actin-coding regions in phylogenetic analyses provides support for the separation of angiosperm actins into two classes. N-terminal "signature" sequence analyses support these groupings. One class (VEG) includes actin genes that are often expressed in vegetative structures. The second class (REP) includes actin genes that trace their ancestry within the vegetative actins and contains members that are largely expressed in reproductive structures. Analysis of intron positions within actin genes shows that sequences from both Selaginella and Cosmarium contain the conserved 20-3, 152-1, and 356-3 introns found in many members of the Streptophyta. In addition, the Cosmarium actin gene contains a novel intron at position 76-1.  (+info)

Thaumatin production in Aspergillus awamori by use of expression cassettes with strong fungal promoters and high gene dosage. (6/5148)

Four expression cassettes containing strong fungal promoters, a signal sequence for protein translocation, a KEX protease cleavage site, and a synthetic gene (tha) encoding the sweet protein thaumatin II were used to overexpress this protein in Aspergillus awamori lpr66, a PepA protease-deficient strain. The best expression results were obtained with the gdhA promoter of A. awamori or with the gpdA promoter of Aspergillus nidulans. There was good correlation of tha gene dosage, transcript levels, and thaumatin secretion. The thaumatin gene was expressed as a transcript of the expected size in each construction (1.9 or 1.4 kb), and the transcript levels and thaumatin production rate decayed at the end of the growth phase, except in the double transformant TB2b1-44-GD5, in which secretion of thaumatin continued until 96 h. The recombinant thaumatin secreted by a high-production transformant was purified to homogeneity, giving one major component and two minor components. In all cases, cleavage of the fused protein occurred at the KEX recognition sequence. This work provides new expression systems in A. awamori that result in very high levels of thaumatin production.  (+info)

Amyloid precursor protein metabolism in fibroblasts from individuals with one, two or three copies of the amyloid precursor protein (APP) gene. (7/5148)

Protein kinase C (PKC)-activated modulation of amyloid precursor protein (APP) metabolism has been investigated in natural models of altered APP expression due to the presence of one, two or three copies of the APP gene. We show that levels of APP present in human skin fibroblasts strongly influence the effect of PKC activation of soluble APP (sAPP) release. Thus fibroblasts derived from a patient with a deletion in chromosome 21 including the APP locus (Delta21) had lower levels of both APP mRNA and cell-associated APP, and showed an exaggerated phorbol-ester-induced sAPP release, when compared with fibroblasts from control individuals. In contrast, fibroblasts from chromosome 21 trisomic Down's syndrome patients failed to show a concentration-dependent response to phorbol ester treatment. These results suggest that the levels of APP expression can affect the degree of response to PKC-mediated modulation of the metabolism of this protein.  (+info)

Der(22) syndrome and velo-cardio-facial syndrome/DiGeorge syndrome share a 1.5-Mb region of overlap on chromosome 22q11. (8/5148)

Derivative 22 (der[22]) syndrome is a rare disorder associated with multiple congenital anomalies, including profound mental retardation, preauricular skin tags or pits, and conotruncal heart defects. It can occur in offspring of carriers of the constitutional t(11;22)(q23;q11) translocation, owing to a 3:1 meiotic malsegregation event resulting in partial trisomy of chromosomes 11 and 22. The trisomic region on chromosome 22 overlaps the region hemizygously deleted in another congenital anomaly disorder, velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS). Most patients with VCFS/DGS have a similar 3-Mb deletion, whereas some have a nested distal deletion endpoint resulting in a 1.5-Mb deletion, and a few rare patients have unique deletions. To define the interval on 22q11 containing the t(11;22) breakpoint, haplotype analysis and FISH mapping were performed for five patients with der(22) syndrome. Analysis of all the patients was consistent with 3:1 meiotic malsegregation in the t(11;22) carrier parent. FISH-mapping studies showed that the t(11;22) breakpoint occurred in the same interval as the 1.5-Mb distal deletion breakpoint for VCFS. The deletion breakpoint of one VCFS patient with an unbalanced t(18;22) translocation also occurred in the same region. Hamster-human somatic hybrid cell lines from a patient with der(22) syndrome and a patient with VCFS showed that the breakpoints occurred in an interval containing low-copy repeats, distal to RANBP1 and proximal to ZNF74. The presence of low-copy repetitive sequences may confer susceptibility to chromosome rearrangements. A 1.5-Mb region of overlap on 22q11 in both syndromes suggests the presence of dosage-dependent genes in this interval.  (+info)

Association of genetic copy number variations at 11 q14.2 with brain regional volume differences in an alcohol use disorder population Journal Article ...
It has been suggested that a high EGFR gene copy number may be an indicator of good response to EGFR tyrosine kinase inhibitor therapy and a marker of poor prognosis in NSCLC. However, imaging features related to EGFR gene copy number status in adenocarcinoma are still unknown. We therefore retrospectively analyzed CT, FDG-PET, and histopathologic slides of surgical resected lung adenocarcinoma in 132 patients. Tumor characteristics on preoperative chest-CT, such as, GGO proportions, tumor diameters, and cavitation; FDG-PET SUV(max); and histopathologically determined differentiation degrees and tumor subtypes were evaluated. EGFR gene copy number status was categorized as FISH-positive or -negative. FISH-positivity was found in 53 patients (40.2%) and was significantly more frequent in tumors with a SUV(max),7.0 (P=0.007). Furthermore, FISH-negativity was found to be more frequent in tumors with a GGO,50% (P=0.023) and diameter ,15.5mm (P=0.006) on CT, or a well-differentiated histopathology ...
Deregulation of the EGFR signaling pathway is one of the most frequently observed genetic abnormalities that drives cancer development. Although mutations in the downstream components of the EGFR signaling pathway, including KRAS, BRAF and PIK3CA, have been reported in numerous cancers, extensive mutation and copy number analysis of these genes in clinical samples has not been performed for head and neck squamous cell carcinoma (HNSCC). We examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. We used DNA sequencing to detect mutations and the copy number changes were evaluated by qPCR and array comparative genomic hybridization (CGH) analysis. We examined the mutations and copy number alterations of KRAS, BRAF and PIK3CA in 115 clinical specimens of HNSCC obtained from surgically treated patients. We identified 3 mutations (2.6%) in K-RAS and 3 mutations (2.6%) in PIK3CA. Copy number amplification was
The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.. ...
Changes in gene and chromosome copy number are widely observed in systems from cancer to drug resistance to genome evolution. Despite the importance of aneuploi...
Rasmussen M, Sundström M, Göransson Kultima H, Botling J, Micke P, Birgisson H, Glimelius B, Isaksson A Genome Biol. 12 (10) R108 [2011-10-24; online 2011-10-24] We describe a bioinformatic tool, Tumor Aberration Prediction Suite (TAPS), for the identification of allele-specific copy numbers in tumor samples using data from Affymetrix SNP arrays. It includes detailed visualization of genomic segment characteristics and iterative pattern recognition for copy number identification, and does not require patient-matched normal samples. TAPS can be used to identify chromosomal aberrations with high sensitivity even when the proportion of tumor cells is as low as 30%. Analysis of cancer samples indicates that TAPS is well suited to investigate samples with aneuploidy and tumor heterogeneity, which is commonly found in many types of solid tumors. Affiliated researcher QC bibliography QC xrefs PubMed 22023820. DOI 10.1186/gb-2011-12-10-r108. Crossref 10.1186/gb-2011-12-10-r108. ...
DNA copy number alterations in 146 bladder tumors.A) Whole genome heatmap representing relative copy number profiles of the samples. Segments of gains or deleti
TY - JOUR. T1 - A versatile statistical analysis algorithm to detect genome copy number variation. AU - Daruwala, Raoul Sam. AU - Rudra, Archisman. AU - Ostrer, Harry. AU - Lucito, Robert. AU - Wigler, Michael. AU - Mishra, Bud. PY - 2004/11/16. Y1 - 2004/11/16. N2 - We have developed a versatile statistical analysis algorithm for the detection of genomic aberrations in human cancer cell lines. The algorithm analyzes genomic data obtained from a variety of array technologies, such as oligonucleotide array, bacterial artificial chromosome array, or array-based comparative genomic hybridization, that operate by hybridizing with genomic material obtained from cancer and normal cells and allow detection of regions of the genome with altered copy number. The number of probes (i.e., resolution), the amount of uncharacterized noise per probe, and the severity of chromosomal aberrations per chromosomal region may vary with the underlying technology, biological sample, and sample preparation. Constrained ...
Complement component 4 (C4) gene copy number (GCN) affects the susceptibility to systemic lupus erythematosus (SLE) in different populations, however the possible phenotype significance remains to be determined. This study aimed to associate C4A, C4B and total C4 GCN and SLE, focusing on the clinical phenotype and disease progression. C4, C4A and C4B GCN were determined by real-time PCR in 427 SLE patients and 301 healthy controls, which underwent a detailed clinical evaluation according to a pre-established protocol. The risk of developing SLE was 2.62 times higher in subjects with low total C4 GCN (| 4 copies, OR = 2.62, CI = 1.77 to 3.87, p | 0.001) and 3.59 times higher in subjects with low C4A GCN (| 2 copies; OR = 3.59, CI = 2.15 to 5.99, p | 0.001) compared to those subjects with normal or high GCN of total C4 (≥4) and C4A (≥2), respectively. An increased risk was also observed regarding low C4B GCN, albeit to a lesser degree (OR = 1.46, CI = 1.03 to 2.08, p = 0.03). Furthermore, subjects
Diagnosing constitutional pathogenic copy number variants (CNVs) requires detecting submicroscopic segmental chromosomal imbalances
Sequencing technology is increasingly demonstrating the impact of genomic copy number variation (CNV) on phenotypes. Opposing variation in growth, head size, cognition and behaviour is known to result from deletions and reciprocal duplications of some genomic regions. We propose normative inversion of face shape, opposing difference from a matched norm, as a basis for investigating the effects of gene dosage on craniofacial development. We use dense surface modelling techniques to match any face (or part of a face) to a facial norm of unaffected individuals of matched age, sex and ethnicity and then we reverse the individuals face shape differences from the matched norm to produce the normative inversion. We demonstrate for five genomic regions, 4p16.3, 7q11.23, 11p15, 16p13.3 and 17p11.2, that such inversion for individuals with a duplication or (epi)-mutation produces facial forms remarkably similar to those associated with a deletion or opposite (epi-)mutation of the same region, and vice versa. The
Women more frequently than men have a type of gene mutation linked to schizophrenia and other neuropsychiatric illnesses, but that doesnt translate into increased risk for the condition.
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Identifying genetic cues of functional relevance is key to understanding the drivers of evolution and increasingly important for the conservation of biodiversity. This study introduces nuclear ribosomal DNA (nrDNA) to mitochondrial DNA (mtDNA) copy number ratios as a metric with which to screen for this functional genetic variation prior to more extensive omics analyses. To illustrate the metric, quantitative PCR was used to estimate nrDNA (18S) to mtDNA (16S) copy number ratios in muscle tissue from samples of two zooplankton species: Salpa thompsoni caught near Elephant Island (Southern Ocean) and S. fusiformis sampled off Gough Island (South Atlantic). Average 18S:16S ratios in these samples were 9:1 and 3:1, respectively. nrDNA 45S arrays and mitochondrial genomes were then deep sequenced to uncover the sources of intra-individual genetic variation underlying these 18S:16S copy number differences. The deep sequencing profiles obtained were consistent with genetic changes resulting from ...
Importantly, when creating the mimicked data sets we did not generate any simulated ratio values; rather, we formed different selections of values using real experimental data. We believe that this use of real experimental data is of significance for aCGH data. This belief is founded on that, in contrast to expression levels, copy number levels are restricted to a, by comparison, moderate dynamic range. Therefore, when a genomic region is subjected to gain or amplification, the increase of genomic material is relatively substantial. Thus, we reasoned that probes for regions of gain would yield comparably higher average intensities than those for regions of normal copy number and that this, in turn, would result in a correlation between M and A: probes measuring ratios of gain will have higher average intensities. The opposite relationship would apply for probes measuring ratios of loss. Consequently, utilizing normalization strategies based on Lowess would possibly correct for correlations ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
inproceedings{8564264, author = {{Mus, Liselot and Denecker, Geertrui and Zeltner, Nadja and Ogando, Yudelca and Van Haver, Stéphane and Sanders, Ellen and Jacobs, Eva and Popovic, Mina and Van Neste, Christophe and Vanhauwaert, Suzanne and Durinck, Kaat and Menten, Björn and De Preter, Katleen and Heindryckx, Björn and Studer, Lorenz and Roberts, Stephen and Speleman, Franki}}, booktitle = {{Advances in Neuroblastoma Research, Congress abstracts}}, language = {{eng}}, location = {{San Fransisco, CA, USA}}, title = {{Exploring the contribution of gene dosage effects of 17q gain on ESC and neuroblastoma proliferation}}, year = {{2018 ...
A research team led by Associate Professor Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL) has developed a sensitive and accurate way of identifying gene copy number variations (CNVs). The method, which is ...
Accurate assignment of copy number at known copy number variant (CNV) loci is important for both increasing understanding of the structural evolution of genomes as well as for carrying out association studies of copy number with disease. As with calling SNP genotypes, the task can be framed as a clustering problem but for a number of reasons assigning copy number is much more challenging. CNV assays have lower signal-to-noise ratios than SNP assays, often display heavy tailed and asymmetric intensity distributions, contain outlying observations and may exhibit systematic technical differences among different cohorts. In addition, the number of copy-number classes at a CNV in the population may be unknown a priori. Due to these complications, automatic and robust assignment of copy number from array data remains a challenging problem. We have developed a copy number assignment algorithm, CNVCALL, for a targeted CNV array, such as that used by the Wellcome Trust Case Control Consortiums recent CNV
Large deletions encompassing the NF1 gene and its flanking regions belong to the group of genomic disorders caused by copy number changes that are mediated by the local genomic architecture. Although nonallelic homologous recombination (NAHR) is known to be a major mutational mechanism underlying such genomic copy number changes, the sequence determinants of NAHR location and frequency are still poorly understood since few high-resolution mapping studies of NAHR hotspots have been performed to date. Here, we have characterized two NAHR hotspots, PRS1 and PRS2, separated by 20 kb and located within the low-copy repeats NF1-REPa and NF1-REPc, which flank the human NF1 gene region. High-resolution mapping of the crossover sites identified in 78 type 1 NF1 deletions mediated by NAHR indicated that PRS2 is a much stronger NAHR hotspot than PRS1 since 80% of these deletions exhibited crossovers within PRS2, whereas 20% had crossovers within PRS1. The identification of the most common strand exchange ...
Purpose: As genome-scale technologies begin to unravel the complexity of the equivalent tumors in adults, we can attempt detailed characterization of high-grade gliomas in children, that have until recently been lacking. Toward this end, we sought to validate and extend investigations of the differences between pediatric and adult tumors.. Experimental Design: We carried out copy number profiling by array comparative genomic hybridization using a 32K bacterial artificial chromosome platform on 63 formalin-fixed paraffin-embedded cases of high-grade glioma arising in children and young people (,23 years).. Results: The genomic profiles of these tumors could be subclassified into four categories: those with stable genomes, which were associated with a better prognosis; those with aneuploid and those with highly rearranged genomes; and those with an amplifier genotype, which had a significantly worse clinical outcome. Independent of this was a clear segregation of cases with 1q gain (more common in ...
View article as PDF. In recent years, we have dramatically changed our view of human genome, from a collection of DNA base pairs that was largely quite stable to one whose very structure can change. Weve learned that higher-order structural features, such as specific configurations of repeated base pair sequences, can predispose for DNA rearrangements.1. One of the most intriguing types of DNA rearrangements is copy-number variants (CNVs), deletions or duplications of parts of the genome. While CNVs range in size from a few hundred base pairs to several mega-bases affecting the copy number of one to dozens of juxtaposed genes, they are not identifiable by conventional light microscopy. It was not until a few years ago that improved technology enabled us to perform high-resolution genome-wide surveys of CNVs in individual genomes. These surveys revealed a large amount of copy number variation (at least 12,000 CNVs overlapping more than 1,000 genes), most of which represent benign polymorphic ...
4468 Detecting the genetic changes associated with cancer development and progression is a major focus in current cancer research. We have developed a high-resolution technology to assess DNA copy number changes in cancer and other diseases. The method combines our whole genome sampling analysis (WGSA), which genotypes over 100,000 single nucleotide polymorphisms (SNPs) from nanogram quantities of human genomic DNA, and our chromosomal copy number tool (CCNT). CCNT can detect regions of chromosomal deletion, amplification, and loss of heterozygosity (LOH). Copy number changes are calculated based on SNP hybridization signal intensity data from the experimental sample relative to intensity distributions derived from a reference set containing over 100 individuals. CCNT also provides a statistical significance of this intensity difference. Several advantages of this technique include the simultaneous collection of genotype information and DNA copy number changes, no requirement of a reference ...
MYC copy gain, chromosomal instability and PI3K activation as potential markers of unfavourable outcome in trastuzumab-treated patients with metastatic breast cancer. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Purpose: The expression of HAGE as a novel prognostic and predictive tool was assessed in 1079 TNBCs. Experimental Design: HAGE protein expression was investigated in an early primary TNBC (EP-TNBC; n=520) cohort who received adjuvant chemotherapy (ACT) and in a locally advanced primary TNBC cohort who received anthracycline-combination Neo-ACT (n=110; AC-Neo-ACT). HAGE-mRNA expression was evaluated in the METABRIC-TNBC-cohort (n=311) who received ACT and in a cohort of patients with TNBC who received doxorubicin/cyclophosphamide Neo-ACT, followed by 1:1 randomisation to ixabepilone (n=68) or paclitaxel (n=64) as part of a phase II clinical trial. Furthermore, a cohort of 128 tumours with integrated HAGE gene copy number changes, mRNA and protein levels were analysed. Results: In patients with EP-TNBC, who were chemotherapy-naïve, high HAGE protein expression (HAGE+) was associated with a higher risk of death (HR: 1.3; 95% CI: 1.2-1.5; p=0.000005) when compared HAGE- cases. Patients who ...
By using {\em E. coli} cells in which the unique origin of replication has been moved to a ectopic chromosome location distant from the native one, we probe how perturbation of gene order near the origin of replication impacts genome stability and survival under genomic attack. We find that when challenged with sub-inhibitory doses of ciprofloxacin, an antibiotic that generates replication fork stalling, cells with the ectopic origin show significant fitness loss. We show that genes functionally relevant to the cipro-induced stress response are largely located near the native origin, even in distantly related species. We show that while cipro induces increased copy number of genes proximal to the origin of replication as a direct consequence of replication fork stalling, gene copy number variation was reduced near the ectopic origin. Altered gene dosage in cells with an ectopic origin resulted in impaired replication fork repair and chromosome instability. We propose that gene distribution in ...
These results highlight the benefits of using CNstream, a method for whole-genome CNV discovery and genotyping for Illumina BeadChip arrays. The present method combined a single-locus scoring approach that takes advantage of the joint clustering analysis of all the intensity samples at each probe with the computational speed and analytical accuracy of estimating CNPs from segments of consecutive probes. Compared with PennCNV, CNstream has superior sensitivity in several common CNPs and it can identify different CNPs that are not detected by PennCNV. The CNP detected by CNstream was demonstrated to be the most significantly associated with RA susceptibility using available RT-PCR technology.. With regard to the single-locus scoring method, CNstream reduced the processing time by robustly initializing the GMM before the EM procedure. This allows a whole-genome analysis to be carried out without the need for previously defined CNP maps, which are required for the SCIMM method. In addition, in ...
Bioconductor version: Release (3.6) The CINdex package addresses important area of high-throughput genomic analysis. It allows the automated processing and analysis of the experimental DNA copy number data generated by Affymetrix SNP 6.0 arrays or similar high throughput technologies. It calculates the chromosome instability (CIN) index that allows to quantitatively characterize genome-wide DNA copy number alterations as a measure of chromosomal instability. This package calculates not only overall genomic instability, but also instability in terms of copy number gains and losses separately at the chromosome and cytoband level.. Author: Lei Song, Krithika Bhuvaneshwar, Yue Wang, Yuanjian Feng, Ie-Ming Shih, Subha Madhavan, Yuriy Gusev Maintainer: Yuriy Gusev ,yg63 at georgetown.edu, ...
Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with map …
Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME). In addition, genetic variation in factors encoding the major histocompatibility complex have been helpful to predict immune-mediated drug toxicity. This knowledge has been translated into clinical applications through the implementation of pharmacogenomic biomarkers. Over 230 of such markers that can, to a certain extent, predict drug efficacy or the ...
FISH-positive criteria have been used according to the corresponding genes. FGFR1 high-level amplification is defined as copy number ≥ 9 or (1) an FGFR1/CEP8 ratio of ≥ 2.0, (2) the average number of FGFR1 signals per tumor cell nucleus ≥ 6, and (3) the percentage of tumor cells containing ≥ 15 FGFR1 signals or large clusters ≥ 10% [74,87]. According to previously published criteria, the EGFR gene copy number was classified into six FISH strata: disomy (two or fewer copies in more than 90% of cells), low trisomy (two or fewer copies in 40% or more of the cells, three copies in 10%-40% of cells, and four or more copies in less than 10% of cells), high trisomy (two or fewer copies in ≥ 40% of cells, three copies in ≥ 40% of cells, and four or more copies in less than 10% of cells), low polysomy (four or more copies in 10%-40% of cells), high polysomy (four or more copies in 40% of the cells or more), and gene amplification (defined by the presence of tight EGFR clusters and a ratio ...
TY - JOUR. T1 - Chromosome 18 gene dosage map 2.0. AU - Cody, Jannine D.. AU - Heard, Patricia. AU - Rupert, David. AU - Hasi-Zogaj, Minire. AU - Hill, Annice. AU - Sebold, Courtney. AU - Hale, Daniel. PY - 2018/12/1. Y1 - 2018/12/1. N2 - In 2009, we described the first generation of the chromosome 18 gene dosage maps. This tool included the annotation of each gene as well as each phenotype associated region. The goal of these annotated genetic maps is to provide clinicians with a tool to appreciate the potential clinical impact of a chromosome 18 deletion or duplication. These maps are continually updated with the most recent and relevant data regarding chromosome 18. Over the course of the past decade, there have also been advances in our understanding of the molecular mechanisms underpinning genetic disease. Therefore, we have updated the maps to more accurately reflect this knowledge. Our Gene Dosage Map 2.0 has expanded from the gene and phenotype maps to also include a pair of maps ...
Dr Liesbeth Lenaerts talks to ecancer at ESMO 2018 about a pre-existing pre-natal test which flagged up copy number alterations and cancer in the foetus'
AbstractLow FCGR3 copy numbers (CNs) has been associated with susceptibility to several systemic autoimmune diseases. However, inconsistent associations were reported and errors caused by shaky methods were suggested to be the major causes. In large scale case control association studies, robust copy number determination method is thus warranted, which was the main focus of the current study. In the present study, FCGR3 CNs of 90 HapMap Asians were firstly checked using four assays including paralogue ratio test combined with restriction enzyme digest variant ratio (PRT-REDVR), real-time quantitative (qPCR) using TaqMan assay, real-time qPCR using SYBR Green dye and short tenden repeat (STR). To improve the comparison precision reproductively, the results were compared with those from recently released sequencing data from 1000 genomes project as well as whole-genome tiling BAC array data. The tendencies of inconsistent samples by these methods were also characterized. Refined in-home TaqMan qPCR assay
Faster implementation of CRLMM specific to SNP 5.0 and 6.0 arrays, as well as a copy number tool specific to 5.0, 6.0, and Illumina platforms.
Pearson and Spearman correlation coefficients are commonly used to quantify the strength of bivariate associations of genomic variables. For example, correlations of gene-level DNA copy number and gene expression measurements may be used to assess the impact of DNA copy number changes on gene expression in tumor tissue. MVisAGe enables users to quickly compute and visualize the correlations in order to assess the effect of regional genomic events such as changes in DNA copy number or DNA methylation level. Please see Walter V, Du Y, Danilova L, Hayward MC, Hayes DN, 2018. Cancer Research ,doi:10.1158/0008-5472.CAN-17-3464,.. ...
Molecular Cloning, also known as Maniatis, has served as the foundation of technical expertise in labs worldwide for 30 years. No other manual has been so popular, or so influential.
Over the past decade, utilization of microarray technology has flourished in biomedical research. It has evolved rapidly into a revolutionary tool that offers deeper insight into the molecular basis...
Are you proposing a thought experiment in which we subtract all the repeat derived sequences (minus the small proportion of bases that regulate gene expression), and most of the the non regulatory intergenic sequences, reducing intron and intergenic sizes by, say 90%, such that we end up with a small number of short chromosomes (say 50 Mb in size - since we know the current division processes can cope with such a size) but keeping the necessary telomeric and centromeric repeats. This would be done with all members of the human species such that all the current copy number polymorphisms and regulatory snps are maintained and all genes are allowed up to 2000bp of regulatory sequences (although we will allow a proportion of genes to have larger regulatory regions). The ultimate result is a human genome that is say, 90% smaller than the current one. You suggest that the current cellular machinery would be able to cope with this change, such that there would be no viability or evolutionary ...
Genome-wide analysis of copy number changes in breast and colorectal tumors used approaches that can reliably detect homozygous deletions and amplifications. The number of genes altered by major copy number changes-deletion of all copies or amplification of at least twelve copies per cell-averaged thirteen per tumor. These data were integrated with previous mutation analyses of the Reference Sequence genes in these same tumor types to identify genes and cellular pathways affected by both copy number changes and point alterations. Pathways enriched for genetic alterations include those controlling cell adhesion, intracellular signaling, DNA topological change, and cell cycle control. These analyses provide an integrated view of copy number and sequencing alterations on a genome-wide scale and identify genes and pathways that are useful for cancer diagnosis and therapy.
Integrative analysis of multiple layers of molecular profiles, such as somatic mutations, DNA copy-number alterations or mRNA expression, offers an unprecedented opportunity to obtain a comprehensive molecular portrait of an individuals tumor. By looking at the recurrence of the molecular alterations found in an individual and at the location of altered proteins in the human interactome, we can put molecular alterations into clinical and molecular context. This PanorOmic view of personal cancer genomes enables a better understanding and interpretation of the results and increases the diagnostic utility of high throughput methods. The current version of Cancer PanorOmics is 2020_01 ...
Heterokaryons provide a model system in which to examine how tissue-specific phenotypes arise and are maintained. When muscle cells are fused with nonmuscle cells, muscle gene expression is activated in the nonmuscle cell type. Gene expression was studied either at a single cell level with monoclonal antibodies or in mass cultures at a biochemical and molecular level. In all of the nonmuscle cell types tested, including representatives of different embryonic lineages, phenotypes, and developmental stages, muscle gene expression was induced. Differences among cell types in the kinetics, frequency, and gene dosage requirements for gene expression provide clues to the underlying regulatory mechanisms. These results show that the expression of genes in the nuclei of differentiated cells is remarkably plastic and susceptible to modulation by the cytoplasm. The isolation of the genes encoding the tissue-specific trans-acting regulators responsible for muscle gene activation should now be possible. ...
(A) Standard curve for quantitation of DNA copy number. The vertical axis shows copies of target DNA per reaction. The horizontal axis shows the ct values as de
Autor: Kramer, M. et al.; Genre: Zeitschriftenartikel; Im Druck veröffentlicht: 2010-05-01; Keywords: Paralogs; RAB-like; Gene expression; Paralog ratio test; Pyrosequencing; Titel: Analysis of relative gene dosage and expression differences of the paralogs RABL2A and RABL2B by Pyrosequencing.
Video created by The State University of New York for the course Big Data, Genes, and Medicine. After this module, you will be able to 1. List different types of gene alterations. 2. Compare and contrast methods for detecting gene mutations. 3. ...
Key to successful detoxification is to be on the QS Detox Cube protocol a minimum of 3 months and slowly titrate up doses. The Detox Cube includes all three months dosage requirements and additional suggestions for optimal health and safe detoxification.
Aims The clinical significance of TOP2A as a prognostic marker has not been clarified. The aims of this study were to investigate the frequency of TOP2A copy number change; to correlate TOP2A with HER2 status, hormone ...
Card is a stiff paper usually heavier than 200gsm (normal copy paper is usually around 60-80 gsm with heavier craft paper at between 100-160gsm) and comes in a range of finishes.
Unless it was reslabbed, it is a different copy as the GPA sale you mentioned has a different cert number. It also had light tan - ow pages and was graded in December of 2012. The Ebay listing was graded June of 2016 so it could have been resubbed as all I am going on is the cert number and no scan of the GPA sale ...
Deviation of gene expression from normal levels has been associated with diseases. Both under- and overexpression of genes could lead to deleterious biological consequences. Dosage balance has been proposed to be a key issue of determining gene expression phenotype. Gene deletion or overexpression of any component in a protein complex produces abnormal phenotypes. As a result, interacting partners should be co-expressed to avoid dosage imbalance effects. The strength of transcriptional co-regulation of interacting partners is supposed to reflect gene dosage sensitivity. Although many cases of dosage imbalance effects have been reported, the molecular attributes determining dosage sensitivity remain unknown. This thesis uses a protein structure analysis protocol to explore the molecular basis of gene dosage sensitivity, and studies the post-transcriptional regulation of dosage sensitive genes. Solvent-exposed backbone hydrogen bond (SEBH or called as dehydron) provides a structure marker for ...
Genomic aberrations in the form of subchromosomal DNA copy number changes are a hallmark of epithelial cancers, including breast cancer. The goal of the present study was to analyze such aberrations in breast cancer at high resolution. We employed high-resolution array comparative genomic hybridization with 4,134 bacterial artificial chromosomes that cover the genome at 0.9 megabase resolution to analyze 47 primary breast tumors and 18 breast cancer cell lines. Common amplicons included 8q24.3 (amplified in 79% of tumors, with 5/47 exhibiting high level amplification), 1q32.1 and 16p13.3 (amplified in 66% and 57% of tumors, respectively). Moreover, we found several positive correlations between specific amplicons from different chromosomes, suggesting the existence of cooperating genetic loci. Queried by gene, the most frequently amplified kinase was PTK2 (79% of tumors), whereas the most frequently lost kinase was PTK2B (hemizygous loss in 34% of tumors). Amplification of ERBB2 as measured by
The recent genome-wide allele-specific copy number variation data enable us to explore two types of genomic information including chromosomal genotype variations as well as DNA copy number variations. For a cancer study, it is common to collect data for paired normal and tumor samples. Then, two types of paired data can be obtained to study a disease subject. However, there is a lack of methods for a simultaneous analysis of these four sequences of data. In this study, we propose a statistical framework based on the change-point analysis approach. The validity and usefulness of our proposed statistical framework are demonstrated through the simulation studies and applications based on an experimental data set.
Copy number analysis usually refers to the process of analyzing data produced by a test for DNA copy number variation in patients sample. Such analysis helps detect chromosomal copy number variation that may cause or may increase risks of various critical disorders. Copy number variation can be detected with various types of tests such as fluorescent in situ hybridization, comparative genomic hybridization and with high-resolution array-based tests based on array comparative genomic hybridization (or aCGH), SNP array technologies and high resolution microarrays that include copy number probes as well an SNPs. Array-based methods have been accepted as the most efficient in terms of their resolution and high-throughput nature and the highest coverage (choose an array with over 2 million probes) and they are also referred to as Virtual Karyotype. Data analysis for an array-based DNA copy number test can be very challenging though due to very high volume of data that come out of an array platform. ...
In this chapter submicroscopic structural variation is described with a particular focus on copy number variation. There is a growing body of evidence to show that copy number variation is a common and important class of genetic variation. Recent technological advances for mapping the extent of copy number variation including microarray based comparative genomic hybridisation are described, together with the results of large scale surveys of copy number variation among healthy individuals. The consequences of such genetic diversity for gene expression are discussed. The important role of copy number variation in susceptibility to a variety of common multifactorial traits is described including infectious and autoimmune disease. Copy number variation is also discussed in relation to evidence for selection in relation to copy number of the gene encoding salivary amylase and a high starch diet, and in relation to drug metabolism with important consequences for pharmacogenomics.
Recent genome-wide microarray-based research investigations have revealed a high frequency of submicroscopic copy number alterations (CNAs) in the myelodysplastic syndromes (MDS), suggesting microarray-based comparative genomic hybridization (aCGH) has the potential to detect new clinically relevant genomic markers in a diagnostic laboratory. We performed an exploratory study on 30 cases of MDS, myeloproliferative neoplasia (MPN) or evolving acute myeloid leukemia (AML) (% bone marrow blasts ≤ 30%, range 0-30%, median, 8%) by aCGH, using a genome-wide bacterial artificial chromosome (BAC) microarray. The sample data were compared to corresponding cytogenetics, fluorescence in situ hybridization (FISH), and clinical-pathological findings. Previously unidentified imbalances, in particular those considered submicroscopic aberrations (| 10 Mb), were confirmed by FISH analysis. CNAs identified by aCGH were concordant with the cytogenetic/FISH results in 25/30 (83%) of the samples tested. aCGH revealed new
Introduction: Lung cancer, of which 85% is non-small cell (NSCLC), is the leading cause of cancer-related death in the United States. Copy number variations (CNVs) in lung adenocarcinoma do not occur randomly in the genome, but are positionally clustered. However, the functional significance of gene copy number changes remains unclear. We characterized genome-wide copy number profiles in non-small cell lung cancer both positionally and functionally. Methods: A series of 301 tumor samples was collected from NSCLC patients in the Massachusetts General Hospital (MGH), Boston, MA (N=202) and National Institute of Occupational Health in Norway (N=99). Copy numbers were evaluated in genomic DNA extracted from micro-dissected tumor tissue with at least 70% tumor cellularity using dense single nucleotide polymorphism arrays. Inferred copy numbers were obtained with dCHIP, and significance of CNVs for each locus was evaluated with binomial distribution. Gene set enrichment analysis algorithm was used to ...
|i|Background|/i|: C-Myc, a well-known oncogene located on 8q24.12–q24.23, is often amplified and over-expressed in both primary and metastasizing colorectal cancer. In addition, PRL-3 (also known as PTP4A3), a tyrosine phosphatase located on 8q24.3, is amplified in colorectal cancer metastasis. Beside PRL-3 and c-myc, other oncogenes located on the 8q23–24 region might be involved in this process. Therefore, the present study aims to correlate DNA copy number status of a series of genes at 8q23–24 in colorectal cancer at high resolution in correlation to metastatic disease. |i|Materials and Methods|/i|: Thirty-two cases of colorectal cancer, 10 stage B1, 10 B2 and 12 D (Astler–Coller) with their corresponding liver metastasis and one colorectal cell line (colo205, previously analyzed by array-CGH), were included in this study. A chromosome 8 specific MLPA probe mixture was used to analyze the presence of DNA copy number changes. The probe mixture contained 29 probes covering
Background: Congenital malformations are present in approximately 2-3% of liveborn babies and 20% of stillborn fetuses. The mechanisms underlying the majority of sporadic and isolated congenital malformations are poorly understood, although it is hypothesized that the accumulation of rare genetic, genomic and epigenetic variants converge to deregulate developmental networks. Methodology/Principal Findings: We selected samples from 95 fetuses with congenital malformations not ascribed to a specific syndrome (68 with isolated malformations, 27 with multiple malformations). Karyotyping and Multiplex Ligation-dependent Probe Amplification (MLPA) discarded recurrent genomic and cytogenetic rearrangements. DNA extracted from the affected tissue (46%) or from lung or liver (54%) was analyzed by molecular karyotyping. Validations and inheritance were obtained by MLPA. We identified 22 rare copy number variants (CNV) [,100 kb, either absent (n = 7) or very uncommon (n = 15, ,1/2,000) in the control ...
From a number of genome-wide association studies it was shown that de novo and/or rare copy number variants (CNVs) are found at an increased frequency in neuropsychiatric diseases. In this study we examined the prevalence of CNVs in six genomic regions (1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, and 16p11.2) previously implicated in neuropsychiatric diseases. Hereto, a cohort of four neuropsychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and intellectual disability) and control individuals from three different populations was used in combination with Multilpex Amplicon Quantifiaction (MAQ) assays, capable of high resolution (kb range) and custom-tailored CNV detection. Our results confirm the etiological candidacy of the six selected CNV regions for neuropsychiatric diseases. It is possible that CNVs in these regions can result in disturbed brain development and in this way lead to an increased susceptibility for different neuropsychiatric disorders, dependent on ...
Uveal melanomas (UM) are aggressive ocular tumours of adults that are typically characterized by chromosomal aberrations such as loss of 1p, 3, 6q, and gain 6p, and 8q. Of these monosomy 3 (M3) and 8q+ are powerful predictors of prognosis. The relationship of changes affecting chromosome 6 is however more ambivalent, having been linked to both good and poor prognosis, and yet both regions have not been well defined, which suggest the presence of one or more oncogenes in 6p and tumour suppressor gene in 6q. Therefore, different chromosome 6 alterations may have a variable impact on the prognosis of UM, and ultimately contain genes that contribute to the development and metastasis of this disease. It is likely that these changes can act as moderators to the tumour outcome. Although UM disseminates haematogenous with high propensity for the liver, and hepatic involvement reported in over 90% of patients, infrequently some patients will however initially present with metastases in sites other than ...
Mitochondrial dysfunction, generally characterized as a loss of efficiency in oxidative phosphorylation, is a hallmark of aging and a variety of chronic diseases. Mitochondrial dysfunction results in inefficient cellular energy production and in increased levels of reactive oxygen species (ROS) which may damage lipids, proteins, and nucleic acids. Mitochondrial dysfunction also affects the expression of nuclear genes involved in metabolism, growth, differentiation, and apoptosis. All these changes may explain the contribution of mitochondrial dysfunction to chronic and complex human diseases. A major limitation to the routine evaluation of mitochondrial dysfunction in clinical practice is the lack of reliable measures of mitochondrial dysfunction available for clinical use. Mitochondrial DNA copy number (mtDNA-CN) is a promising biomarker of mitochondrial dysfunction that has the potential to become widely available in clinical practice. Other measures of mitochondrial dysfunction, including ...
Abstract: Resistance to chemotherapeutic agents and radiotherapy has kept surgery the primary treatment of uterine leiomyosarcoma (ULMS). In search of leads for potential therapeutic targets, array CGH (aCGH) was used to obtain a genomewide pattern of ULMS-specific genetic imbalances and to define the affected biological processes. Fine-resolution genomewide aCGH analysis was performed using customised 16K cDNA microarrays on 18 primary ULMS cases. Furthermore, patterns of DNA copy number changes were assessed for associations with clinical parameters, i.e., tumour grade, tumour size and patient status at last follow-up. Our aCGH results demonstrated extensive DNA copy number changes in all chromosomes. Of the 10,590 gene loci included in the analysis, 4,387 were found to be affected by DNA copy number gains and 4,518 by DNA copy number losses in at least one case. Further analyses revealed that 231 of these were commonly gained, and 265 lost in at least 20% of the cases. The gains affected loci ...
We have used a new method of genomic microarray to investigate amplification of oncogenes throughout the genome of glioblastoma multiforme (GBM). Array-based comparative genomic hybridization (array CGH) allows for simultaneous examination of 58 oncogenes/amplicons that are commonly amplified in var …
DNA copy number variants represent the greatest source of genetic variability in humans [1] and are the underlying cause of many human diseases. Array CGH is recognized as a first-tier test for DNA copy number variants (CNV) [2] and accordingly, many laboratories have already established their pipelines for pre-processing of array CGH data and CNV calling. In many cases these pipelines are based on software packages provided by the companies selling DNA microarrays or scanners such as BlueFuse [3], CytoSure [4] or CytoGenomics [5]. Yet, the scope of these tools is focused on the identification of CNVs and their evaluation in the context of gene content and frequency of a given variant in the healthy population. Comparative analysis, which integrates data obtained from multiple patients, or other experiment types are hardly supported, in particular when they are based on different array platforms or NGS technology.. Such kind of meta-analysis needs the implementation of additional commercial or ...
Oncogenic point mutations in KIT or PDGFRA are recognized as the primary events responsible for the pathogenesis of most gastrointestinal stromal tumors (GIST), but additional genomic alterations are frequent and presumably required for tumor progression. The relative contribution of such alterations for the biology and clinical behavior of GIST, however, remains elusive. In the present study, somatic mutations in KIT and PDGFRA were evaluated by direct sequencing analysis in a consecutive series of 80 GIST patients. For a subset of 29 tumors, comparative genomic hybridization was additionally used to screen for chromosome copy number aberrations. Genotype and genomic findings were cross-tabulated and compared with available clinical and follow-up data. We report an overall mutation frequency of 87.5%, with 76.25% of the tumors showing alterations in KIT and 11.25% in PDGFRA. Secondary KIT mutations were additionally found in two of four samples obtained after imatinib treatment. Chromosomal imbalances
About a decade ago the first large catalogs of copy number variants (CNVs) in the human genome were presented [1, 2]. Numerous studies later, CNVs are known to contribute to the genomic variation to a larger extent than single nucleotide polymorphisms (SNPs) in terms of number of nucleotide differences [3, 4]. CNVs are defined as DNA segments of variable length, up to several megabases (Mb), that varies in copy numbers in comparison to a reference genome [5]. The different types of CNVs include deletions and duplications, while consequences of CNVs include e.g. altered gene dosage and regulation, changed gene structure and unmasking of recessive alleles [5]. The effect of CNVs varies from being benign or neutral, to having subtle effects on disease predisposition or directly causing disease. The contribution and importance of CNVs for phenotypic diversity and disease susceptibility has been repeatedly shown in human and several complex diseases such as psoriasis, Crohns disease, type 2 ...
Arabidopsis thaliana is the model plant and is grown worldwide by plant biologists seeking to dissect the molecular underpinning of plant growth and development. Gene copy number variation (CNV) is a common form of genome natural diversity that is currently poorly studied in plants and may have broad implications for model organism research, evolutionary biology, and crop science. Herein, comparative genomic hybridization (CGH) was used to identify and interrogate regions of gene CNV across the A. thaliana genome. A common temperature condition used for growth of A. thaliana in our laboratory and many around the globe is 22 degrees C. The current study sought to test whether A. thaliana, grown under different temperature (16 and 28 degrees C) and stress regimes (salicylic acid spray) for five generations, selecting for fecundity at each generation, displayed any differences in CNV relative to a plant lineage growing under normal conditions. Three siblings from each alternative temperature or stress
The treatment strategy usually depends on the disease state in the individual patient. However, it is difficult to estimate the disease state before treatment in many patients. The purpose of this study was to develop a BAC (bacterial artificial chromosome) mini-array allowing for the estimation of node metastasis, liver metastasis, peritoneal dissemination and the depth of tumor invasion in gastric cancers. Initially, the DNA copy number aberrations (DCNAs) were analyzed by array-based comparative genomic hybridization (aCGH) in 83 gastric adenocarcinomas as a training-sample set. Next, two independent analytical methods were applied to the aCGH data to identify the BAC clones with DNA copy number aberrations that were linked with the disease states. One of the methods, a decision-tree model classifier, identified 6, 4, 4, 4, and 7 clones for estimating lymph node metastasis, liver metastasis, peritoneal dissemination, depth of tumor invasion, and histological type, respectively. In the other method, a
article{39c3420c-566c-4f24-879b-c3929d10ccd7, abstract = {It has been suggested that mitochondrial dysfunction and DNA damage are involved in lymphomagenesis. Increased copy number of mitochondrial DNA (mtDNA) as a compensatory mechanism of mitochondrial dysfunction previously has been associated with B-cell lymphomas, in particular chronic lymphocytic leukemia (CLL). However, current evidence is limited and based on a relatively small number of cases. Using a nested case-control study, we extended these findings with a focus on subtype specific analyses. Relative mtDNA copy number was measured in the buffy coat of prospectively collected blood of 469 lymphoma cases and 469 matched controls. The association between mtDNA copy number and the risk of developing lymphoma and histologic subtypes was examined using logistic regression models. We found no overall association between mtDNA and risk of lymphoma. Subtype analyses revealed, significant increased risks of CLL (n=102) with increasing mtDNA ...
Genomic copy number changes are frequently found in cancers and they have been demonstrated to contribute to carcinogenesis; and it is widely accepted that tumors with microsatellite instability (MSI) are genetically stable and mostly diploid. In the present study we compared the copy number alterations and the gene-expression profiles of microsatellite stable (MSS) and MSI colorectal tumors. A total number of 31 fresh-frozen primary tumors (16 MSS and 15 MSI) were used. Twenty-eight samples (15 MSS and 13 MSI) were analyzed with metaphase comparative genomic hybridization (CGH), nine of which plus one additional sample (4 MSS and 6 MSI) were further analyzed by cDNA-based array-CGH. Gene expression analysis was performed with six samples [3 MSS and 3 MSI, four of these used in metaphase CGH (mCGH) analysis] to identify differentially expressed genes possibly located in the lost or amplified regions found by CGH, stressing the biological significance of copy number changes. Metaphase and ...
We conducted a genome-wide scan for large CNVs (≥100 kb) in a case-control dataset of Caribbean Hispanic origin that was previously investigated in a SNP-based GWAS (Lee JH et al. 2010). To generate results with high confidence, we focused on CNVs that were identified by at least two algorithms. We detected 1774 stringent CNVs (Table S4). First, we tested the hypothesis that rare CNVs (≤1%) with a potentially strong impact on AD risk in individual patients might contribute to the overall disease risk, as was previously observed in other common neuropsychiatric disorders (Kirov et al. 2009; Zhang et al. 2009; Glessner et al. 2010). However, the burden analyses of rare CNVs did not find significant differences between cases and controls in CNV rate, total or average CNV size, or the number of genes affected by CNVs.. In addition, we conducted a case-control analysis of large genic CNVs, including common variants, using PLINK regional analysis. The only nominally significant result that ...
|jats:title|Abstract|/jats:title||jats:p|Long regarded as an epicenter of drug-resistant malaria, Southeast Asia continues to provide new challenges to the control of |jats:italic|Plasmodium falciparum|/jats:italic| malaria. Recently, resistance to the artemisinin combination therapy partner drug piperaquine has been observed in multiple locations across Southeast Asia. Genetic studies have identified a single nucleotide polymorphism as well as a copy number variation molecular marker that associate with clinical and |jats:italic|in vitro|/jats:italic| resistance. The copy number polymorphism is a duplication of a region containing members of the plasmepsin multi-gene family of proteases. To accurately and quickly determine the presence of copy number variation in the |jats:italic|plasmepsin 2/3|/jats:italic| duplication in field isolates, we developed a quantitative PCR assay using TaqMan probes. We validated copy number estimates using a separate SYBR green-based quantitative PCR assay as well as a
Figure Novel compound heterozygous mutation in the COLQ gene causes congenital myasthenic syndrome. (A) Pedigree of the proband (II-1). Point mutation (IVS16+3A→G) in the COLQ gene was inherited from the father (I-1), and multiexon deletion from the mother (I-2). (B) Gene list of 21 known congenital myasthenic syndrome (CMS) genes included in the targeted CMS panel. (C) Genome view of PatternCNV analysis shows decreased copy number variation (CNV) log2 ratio for the COLQ gene in chromosome 3. (D) Exon-level CNV summary table shows the start and end position of deletion (984 base pairs) in the COLQ gene, which indicates 1 copy deletion of exons 14 and 15. SNR.db: signal noise ratio expressed in decibels; CNV.ratio: copy number ratio converted from CNV.log2ratio. CNV.ratio of 1 indicates no copy number change. (E) TaqMan Copy Number Assay results confirm exon deletions in the COLQ gene in the proband, which is also found in her mother (data not shown). Longer PCR cycle number (X-axis) denotes 1 ...
TY - JOUR. T1 - Identification of genes involved in squamous cell carcinoma of the lung using synchronized data from DNA copy number and transcript expression profiling analysis. AU - Lo, Ken C.. AU - Stein, Leighton C.. AU - Panzarella, Jenniffer A.. AU - Cowell, John Kenneth. AU - Hawthorn, Lesleyann. PY - 2008/3/1. Y1 - 2008/3/1. N2 - Lung cancer is the leading cause of cancer deaths in the world and squamous cell carcinoma (SqCC) is the second most common in this group. Genomic DNA copy number alterations are fundamental genetic events in the development and progression of SqCC as well as other epithelial-derived cancers. The ability to identify tumor suppressor genes (TSGs) and oncogenes that are affected during tumor initiation and progression could facilitate the identification of novel molecular targets for therapeutic intervention and provide diagnostic biomarkers. Despite the association of many genetic alterations in lung cancer the molecular mechanisms of tumor progression remain ...
BACKGROUND: Illumina Infinium whole genome genotyping (WGG) arrays are increasingly being applied in cancer genomics to study gene copy number alterations and allele-specific aberrations such as loss-of-heterozygosity (LOH). Methods developed for normalization of WGG arrays have mostly focused on diploid, normal samples. However, for cancer samples genomic aberrations may confound normalization and data interpretation. Therefore, we examined the effects of the conventionally used normalization method for Illumina Infinium arrays when applied to cancer samples. RESULTS: We demonstrate an asymmetry in the detection of the two alleles for each SNP, which deleteriously influences both allelic proportions and copy number estimates. The asymmetry is caused by a remaining bias between the two dyes used in the Infinium II assay after using the normalization method in Illuminas proprietary software (BeadStudio). We propose a quantile normalization strategy for correction of this dye bias. We tested the ...
Richard-Carpentier G, Kantarjian HM, Short NJ, Ravandi F, Ferrajoli A, Schroeder HM, et al. Yang J, Bhojwani D, Yang W. Genome-wide copy number profiling reveals molecular evolution from diagnosis to relapse in childhood acute lymphoblastic leukemia. E. Jabbour has research grants with Amgen, AbbVie, Spectrum, BMS, Takeda Oncology, Pfizer, and Adaptive. Seizures 3. The genomic landscape of high hyperdiploid childhood acute lymphoblastic leukemia. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, et al. Pui CH, Crist WM, Look AT. PubMed Central Google Scholar. Blood. Additional tables. Neumann M, Vosberg S, Schlee C, Heesch S, Schwartz S, Gökbuget N, et al. However, a better understanding of the disease biology has generated important knowledge on the prognostic and predictive value of MRD, which has helped guide our treatment strategies, such as intensification or referral to HSCT, the use of MRD-directed novel agents or even treatment de-escalation. 2016;172(3):392-400. There ...
To select parameters for calling CNVs (that is, the statistical threshold of the ADM2 algorithm, the minimum +/- log2 ratio and the minimum number of consecutive probes in a CNV interval), we calculated the sensitivity and positive predictive value based on the comparison of aCGH-based CNV calls (using our high-resolution Agilent 24M platform) with read-depth sequence data for two samples from Korean individuals (AK1 and AK2). We attempted to obtain `absolute copy number status of the sample from NA10851, which was used as the reference sample for aCGH experiments in this study. For this, we used read-depth data for NA10851 obtained from massively parallel sequencing by the Illumina GA II data. The read-depth data represent the copy number status of NA10851 as compared to the human reference genome (hg18) because the short read sequences were aligned to hg18 ...
Thousands of genomic segments appear to be present in widely varying copy numbers in different human genomes. We developed ways to use increasingly abundant whole-genome sequence data to identify the copy numbers, alleles and haplotypes present at most large multiallelic CNVs (mCNVs). We analyzed 849 genomes sequenced by the 1000 Genomes Project to identify most large (,5-kb) mCNVs, including 3878 duplications, of which 1356 appear to have 3 or more segregating alleles. We find that mCNVs give rise to most human variation in gene dosage-seven times the combined contribution of deletions and biallelic duplications- and that this variation in gene dosage generates abundant variation in gene expression. We describe runaway duplication haplotypes in which genes, including HPR and ORM1, have mutated to high copy number on specific haplotypes. We also describe partially successful initial strategies for analyzing mCNVs via imputation and provide an initial data resource to support such analyses ...
The first estimation of how genomic copy number variation (CNV) can influence anesthetic sensitivity and the magnitude of this influence can be gauged by a new study
A fixed gene copy number is important for the in silico construction of engineered synthetic networks. However, the copy number of integrated genes depends on their genomic location. This gene dosage effect is rarely addressed in synthetic biology. Two studies in Escherichia colipresented conflicting data on the impact of gene dosage. Here, we investigate how genome location and gene orientation influences expression in Bacillus subtilis. An important difference with the E. coli studies is that we used an unbiased genome integration approach mediated by random transposon insertion. We found that there is a strong gene dosage effect in fast growing B. subtilis cells, which can amount to a 5-fold difference in gene expression. In contrast, gene orientation with respect to DNA replication direction does not influence gene expression. Our study shows that gene dosage should be taken into account when designing synthetic circuits in B. subtilis and presumably other bacteria.. ...
Copy number variation can contribute to the variation observed in susceptibility to complex diseases. Here we present the first study to investigate copy number variation of the chemokine gene CCL3L1 with susceptibility to malaria. We present a family-based genetic analysis of a Tanzanian population (n = 922), using parasite load, mean number of clinical infections of malaria and haemoglobin levels as phenotypes. Copy number of CCL3L1 was measured using the paralogue ratio test (PRT) and the dataset exhibited copy numbers ranging between 1 and 10 copies per diploid genome (pdg). Association between copy number and phenotypes was assessed. Furthermore, we were able to identify copy number haplotypes in some families, using microsatellites within the copy variable region, for transmission disequilibrium testing. We identified a high level of copy number haplotype diversity and find some evidence for an association of low CCL3L1 copy number with protection from anaemia.. ...
Copy number variants (CNVs) on the Breakpoint 1 to Breakpoint 2 region Ki8751 at 15q11. of publically obtainable expression data identified a relationship between expression of mRNA and FOXP2 in mind. We suggest that changed medication dosage through aberrant patterning from the lh.SMG may donate to language-related Mouse monoclonal to CD11b.4AM216 reacts with CD11b, a member of the integrin a chain family with 165 kDa MW. which is expressed on NK cells, monocytes, granulocytes and subsets of T and B cells. It associates with CD18 to form CD11b/CD18 complex.The cellular function of CD11b is on neutrophil and monocyte interactions with stimulated endothelium; Phagocytosis of iC3b or IgG coated particles as a receptor; Chemotaxis and apoptosis. Ki8751 issues connected with BP1-2 CNVs. Even more generally this process may be useful in clarifying the contribution Ki8751 of individual genes at CNV risk loci. Introduction Rare multi-gene copy number variants (CNVs) are well established to increase ...
Scientists reported the development of a robust procedure for whole-genome copy number profiling of circulating tumor cells (CTCs) from a blood test. In contrast to existing methods that are complex and costly, the single-tube, single-step protocol detect absolute copy number alterations (CNA) in single cells and maintain accuracy at a lower cost than conventional genomic analysis procedure, opening up to the possibility for genome-driven targeted therapy selection and monitoring of disease progression in liquid biopsy.
The authors profiled either unselected [3-5], triple-negative [1], or estrogen-receptor positive breast cancer [2] utilizing various technical approaches, including whole-genome sequencing, whole-exome sequencing, copy number profiling, and transcriptome analysis. Curtis and colleagues [5] integrate expression and copy number to identify ten subtypes of breast cancers and reveal aberration hotspots responsible for these groups. These hotspots contain known (ERBB2, MYC) and candidate driver loci that can impact patient prognosis. Stephens and colleagues [4] combined copy-number and sequencing to identify a number of novel driver genes (MAP3K1, MAP2K4, MAP3K13, and AKT2), albeit each at relatively low frequency. Together, however, these mutations all impact JUN signaling activation and encompass approximately 50% of all breast tumors, thus identifying a major recurrent pathway alteration in breast cancer. Banerji and colleagues [3] similarly utilize sequencing to identify driver mutations and copy ...
Complex focal chromosomal rearrangements in cancer genomes, also called firestorms, can be scored from DNA copy number data. The complex arm-wise aberration index (CAAI) is a score that captures DNA copy number alterations that appear as focal complex events in tumors, and has potential prognostic value in breast cancer. This study aimed to validate this DNA-based prognostic index in breast cancer and test for the first time its potential prognostic value in ovarian cancer. Copy number alteration (CNA) data from 1950 breast carcinomas (METABRIC cohort) and 508 high-grade serous ovarian carcinomas (TCGA dataset) were analyzed. Cases were classified as CAAI positive if at least one complex focal event was scored. Complex alterations were frequently localized on chromosome 8p (n = 159), 17q (n = 176) and 11q (n = 251). CAAI events on 11q were most frequent in estrogen receptor positive (ER+) cases and on 17q in estrogen receptor negative (ER-) cases. We found only a modest correlation between ...
Author Summary Mutations in noncoding sequence can cause disease but are very difficult to recognize. Here, we present two approaches intended to help identify noncoding regions of the genome that may carry mutations influencing disease. The first approach is based on comparing observed and predicted levels of standing human variation in the noncoding exome sequence of a gene. The second approach is based on the phylogenetic conservation of a genes noncoding exome sequence using GERP++. We find that both approaches can predict genes known to cause disease through changes in expression level, genes depleted of loss-of-function alleles in the general population, and genes permissive of copy number variants in the general population. We find that both scores aid in interpreting loss-of-function mutations and in defining regions of noncoding sequence that are more likely to harbor mutations that influence risk of disease.
BACKGROUND: Tandem repeat variation in protein-coding regions will alter protein length and may introduce frameshifts. Tandem repeat variants are associated with variation in pathogenicity in bacteria and with human disease. We characterized tandem repeat polymorphism in human proteins, using the UniGene database, and tested whether these were associated with host defense roles.. RESULTS: Protein-coding tandem repeat copy-number polymorphisms were detected in 249 tandem repeats found in 218 UniGene clusters; observed length differences ranged from 2 to 144 nucleotides, with unit copy lengths ranging from 2 to 57. This corresponded to 1.59% (218/13,749) of proteins investigated carrying detectable polymorphisms in the copy-number of protein-coding tandem repeats. We found no evidence that tandem repeat copy-number polymorphism was significantly elevated in defense-response proteins (p = 0.882). An association with the Gene Ontology term protein-binding remained significant after covariate ...
Environmental risk factors have been shown to alter DNA copy number variations (CNVs). Recently, CNVs have been described to arise after low-dose ionizing radiation in vitro and in vivo. Development of cost- and size-effective laser-driven electron accelerators (LDEAs), capable to deliver high energy beams in pico- or femtosecond durations requires examination of their biological effects. Here we studied in vitro impact of LDEAs radiation on known CNV hotspots in human peripheral blood lymphocytes on single cell level. Here CNVs in chromosomal regions 1p31.1, 7q11.22, 9q21.3, 10q21.1 and 16q23.1 earlier reported to be sensitive to ionizing radiation were analyzed using molecular cytogenetics. Irradiation of cells with 0.5, 1.5 and 3.0 Gy significantly increased signal intensities in all analyzed chromosomal regions compared to controls. The latter is suggested to be due to radiation-induced duplication or amplification of CNV stretches. As significantly lower gains in mean fluorescence intensities were
Most behavioral, physiological and cellular effects of theneurotransmitter dopamine require concomitant activation of both D1 and D2 receptors, a phenomenon referred to as D1/D2 synergism. Since D1 and D2 receptors are located mostly on separate neurons, and since D1/D2 synergism occurs in the absence of action potentials, we have suggested that electrotonic coupling via gap junctions plays an important role in this phenomenon. A major constituent of gap junctions is connexin36 (Cx36), a protein that is abundant in neurons. The role Cx36 in D1/D2 synergism, as manifested behaviorally, was studied here in mice genetically engineered to express normal, reduced, or undetectable amounts of this protein. The results show that D1/D2 synergism and its breakdown were not affected by the presence or absence of Cx36. Unexpectedly, it was observed that the absence of Cx36 leads to resistance to the cataleptic effects of reserpine in a gene dosage-dependent manner.
Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion , control, duplication). In contrast, gene dosage varied negatively with mean cortical thickness (deletion , control , duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric ...
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"Adipose is a conserved dosage-sensitive antiobesity gene". Cell Metabolism. 6 (3): 195-207. doi:10.1016/j.cmet.2007.08.001. PMC ... Although its discoverers dubbed this gene the adipose gene, it is not a gene responsible for creating adipose tissue. ... Gene defects in the leptin gene (ob) are rare in human obesity.[78] As of July, 2010, only 14 individuals from five families ... Main article: Genetics of obesity § Genes. The thrifty gene hypothesis (also called the famine hypothesis) states that in some ...
Gabriel JM, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Steck AJ (December 1997). "Gene dosage effects in hereditary ... A 2017 Cochrane systematic review found that daily dosages between (1800 - 3600) mg of gabapentin could provide good pain ... even at high dosages (200 - 400) mg. A 2013 Cochrane systematic review of topimirate found that the included data had a strong ...
Gabriel JM, Erne B, Pareyson D, Sghirlanzoni A, Taroni F, Steck AJ (December 1997). "Gene dosage effects in hereditary ...
September 2007). "Adipose is a conserved dosage-sensitive antiobesity gene". Cell Metabolism. 6 (3): 195-207. doi:10.1016/j. ... WDTC1 ("Adipose") is a gene associated with obesity. WDTC1 is a gene that codes for a protein acting as a suppressor in lipid ... "ScienceDaily: 'Skinny Gene' Exists". Retrieved 2007-09-05. Lai CQ, Parnell LD, Arnett DK, García-Bailo B, Tsai MY, Kabagambe EK ... Transgenic expression of the WDTC1 gene in mice showed the opposite effect with mice having less adipose. Suh JM, Zeve D, McKay ...
... discovery of the master control gene involved in sex determination; and studies of gene regulation, particularly dosage ... Meyer's work has revealed mechanisms of sex determination and dosage compensation -- that balance X-chromosome gene expression ... Further analysis of the mechanism underlying dosage compensation produced many key insights into gene regulation. In 1990, ... But it wasn't clear whether the worms accomplished this by upregulating genes on the X chromosome in males or by downregulating ...
... with detection of gene dosage". Am. J. Hum. Genet. 75 (2): 267-281. doi:10.1086/422854. PMC 1216061. PMID 15197683.. ... There may be a gene or genes in the 15q11-q13 region that is/are related to the development of autism in some individuals. ... "Increased Gene Dosage of Ube3a Results in Autism Traits and Decreased Glutamate Synaptic Transmission in Mice". Science ... Array CGH can be used to determine the gene content and magnitude of copy number variation so that the clinical picture can be ...
The dosage-sensitive genes vary from species to species. Birchler JA, Pal-Bhadra M, Bhadra U (March 2003). "Dosage dependent ... Natural selection occurs efficiently in Drosophila so the genes that are dosage-sensitive are increased. ... X hyperactivation is regulated by the alternative splicing of a gene called sex-lethal. The gene was named sex-lethal due to ... The X chromosome, compared to an autosomal gene, contains more silent genes which influences measuring the amount of influence ...
It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area it leads to microcephaly. ... HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2. GJA5 has been identified as the gene ... New genes are expected in the gaps. Because the gaps are still a topic of research, it is hard to find the exact start and end ... In this way the number of chromosomes will be halved in each cell, while all the parts on the chromosome (genes) remain, after ...
It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area, it leads to microcephaly. ... HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2. Research on the genes CHD1L and ... New genes are expected in the gaps. Because the gaps are still a topic of research, it is hard to find the exact start and end ... Genes related to 1q21.1 deletion in the distal area are PDE4DIP, HYDIN2, PRKAB2, PDIA3P, FMO5, CHD1L, BCL9, ACP6, GJA5, GJA8, ...
Acampora, D; Avantaggiato, V; Tuorto, F; Simeone, A (1997). "Genetic control of brain morphogenesis through Otx gene dosage ... In zebrafish, it was shown that the expression of two SHH genes, SHH-a and SHH-b (formerly described as twhh) mark the MDO ... Hirata, T.; Nakazawa, M; Muraoka, O; Nakayama, R; Suda, Y; Hibi, M (2006). "Zinc-finger genes Fez and Fez-like function in the ... SHH signaling from the MDO induces a posterior-to-anterior wave of expression the proneural gene Neurogenin1 in the major ( ...
"Dosage sensitivity and the evolution of gene families in yeast". Nature. 424 (6945): 194-197. Bibcode:2003Natur.424..194P. doi: ... Lercher, M.J.; Urrutia, A.O.; Hurst, L.D. (2002). "Clustering of housekeeping genes provides a unified model of gene order in ... This has resulted in work on housekeeping genes, gene orders, and the evolution of drug resistance in Staphylococcus aureus, ... Similarly, in showing that genomes are arranged into gene expression domains, Hurst revealed that genes can affect the ...
CS1 maint: discouraged parameter (link) Chen, Jianping (2009). Molecular Basis of Gene Dosage Sensitivity (Ph.D.). Rice ... Proline-rich 12 (PRR12) is a protein of unknown function encoded by the gene PRR12. The Homo sapiens PRR12 gene is 34,785 base ... Within its gene neighborhood, PRR12 is flanked by PRRG2 and SCAF1 on the sense strand and RRAS and NOSIP on the antisense ... The gene is moderately expressed at even levels in a wide variety of tissue types. The PRR12 transcript encodes a protein that ...
Papp, Balázs; Pál, Csaba; Hurst, Laurence D. (July 2003). "Dosage sensitivity and the evolution of gene families in yeast". ... They demonstrated that gene loss initiates adaptive genomic changes that rapidly restores fitness, but this process has ... They specifically tested what is now known as the dosage balance hypothesis. The hypothesis offers a synthesis on seemingly ... More recently, the Pal lab explored the consequences of compensatory adaptation on gene content evolution. It is well known ...
1994). "PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system ... regulation of gene expression. • positive regulation of gene expression. • pallium development. • oligodendrocyte cell fate ... "Genes and Mapped Phenotypes." National Center for Biotechnology Information. U.S. Pax6 is a gene in prenatal development ... "Genes & Development. 28 (17): 1879-1884. doi:10.1101/gad.246140.114. ISSN 0890-9369. PMC 4197948 . PMID 25184676.. ...
developed a novel strategy termed "Gene Dosage Network Analysis" (GDNA) to describe network features in the human circadian ... initiates transcription of target genes such as the core clock genes 'period' genes (PER1, PER2, and PER3) and two cryptochrome ... The first genes identified in the plant clock were TOC1, CCA1 and LHY. The peak expression of the CCA1 and LHY genes occurs at ... Characterization of a subset of these genes demonstrated a dosage-dependent effect on oscillator function. Protein interaction ...
"HLA DQ gene dosage and risk and severity of celiac disease". Clinical Gastroenterology and Hepatology. 5 (12): 1406-12. doi: ... is a human gene and also denotes the genetic locus that contains this gene. The protein encoded by this gene is one of two ... "Entrez Gene: HLA-DQB1 major histocompatibility complex, class II, DQ beta 1". Lau M, Terasaki PI, Park MS (1994). " ... 0302 encode genes that mediate the autoimmune coeliac disease. Homozygotes of DQB1*0201 have a higher risk of developing the ...
... q24.2 by in situ hybridization and gene dosage studies, in Cytogenet. Cell Genet., vol. 57, 2-3, 1991, pp. 105-8, DOI:10.1159/ ... Vidaud M, Gattoni R, Stevenin J, et al., A 5' splice-region G----C mutation in exon 1 of the human beta-globin gene inhibits ... Delfau MH, Picat C, de Rooij FW, et al., Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene ... Grandchamp B, Picat C, de Rooij F, et al., A point mutation G----A in exon 12 of the porphobilinogen deaminase gene results in ...
"Dosage analysis of cancer predisposition genes by multiplex ligation-dependent probe amplification". Br. J. Cancer. 91 (6): ... then the dosage quotient DQ = (a/b) / (A/B). Although dosage quotients may be calculated for any pair of amplicons, it is ... detection of gene copy number, detection of duplications and deletions in human cancer predisposition genes such as BRCA1, ... Dosage quotient analysis is the usual method of interpreting MLPA data. If a and b are the signals from two amplicons in the ...
Tissenbaum, H.A.; L. Guarente (2001). "Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans". Nature. ... For the first nine years, his lab studied gene regulation in yeast. In 1991 his lab started to study genes involved in aging. ... In 1993, Cynthia Kenyon's lab at UCSF discovered that a single-gene mutation in (Daf-2) could double the lifespan of C. elegans ... In 1995 the Guarente lab identified the gene SIR4 (Silent information regulator 4) as a longevity regulator. When SIRT4 was ...
Trieu M, Ma A, Eng SR, Fedtsova N, Turner EE (Jan 2003). "Direct autoregulation and gene dosage compensation by POU-domain ... Trieu M, Ma A, Eng SR, Fedtsova N, Turner EE (Jan 2003). "Direct autoregulation and gene dosage compensation by POU-domain ... This can be explained by gene dosage compensation due to autoregulation, in which expression of the remaining copy of the ... "Entrez Gene: POU4F1 POU domain, class 4, transcription factor 1". Gerrero MR, McEvilly RJ, Turner E, Lin CR, O'Connell S, Jenne ...
For example, increasing the gene dosage of the gene SIR-2, which regulates DNA packaging in the nematode worm Caenorhabditis ... Tissenbaum HA, Guarente L (March 2001). "Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans". Nature. ... The gene designations shown in red, gray or cyan indicate genes frequently epigenetically altered in various types of cancers. ... In particular, the gene-rich, early-replicating regions of the human genome exhibit lower mutation frequencies than the gene- ...
Changes in gene dosage, the number of times a given gene is present in the cell nucleus, can create a genetic imbalance. This ... Diminishing the dosage of most genes produces no obvious change in phenotype. For some genes the phenotypic consequences of a ... For some rare genes, the normal diploid level of gene expression is essential to individual survival; fewer than two copies of ... Genetic imbalance is to describe situation when the genome of a cell or organism has more copies of some genes than other genes ...
The alteration in the gene dosage, which is caused by the loss of a functional allele, is also called allelic insufficiency. An ... The haploinsufficiency is caused by the copy-number variation (CNV) of 28 genes led by the deletion of ~1.6 Mb. These dosage- ... This leads to too many or too few of the dosage sensitive genes. The genomic rearrangements, that is, deletions or duplications ... A mutation in the gene may have erased the production message. One of the two copies of the gene may be missing due to a ...
Huang GY, Wessels A, Smith BR, Linask KK, Ewart JL, Lo CW (1998). "Alteration in connexin 43 gap junction gene dosage impairs ... Thus, B-catenin is stabilized in the presence of Wnt and regulates gene transcription through interaction with TCF/LEF ... Cardiac neural crest cells express Hox genes that supports the development of arteries 3, 4 and 6 and the simultaneous ... regression of arteries 1 and 2. The ablation of Hox genes on cardiac neural crest cells causes defective outflow septation. One ...
Since individuals of either sex will receive two copies of every gene in a pseudoautosomal region, no dosage compensation is ... in females that are heterozygous at the involved gene or genes than in females that are homozygous at that gene or those genes. ... meaning that the Tsix gene overlaps the Xist gene and is transcribed on the opposite strand of DNA from the Xist gene.[31] Tsix ... Expressed genes on the inactive X chromosome[edit]. A fraction of the genes along the X chromosome escape inactivation on the ...
Since individuals of either sex will receive two copies of every gene in a pseudoautosomal region, no dosage compensation is ... in females that are heterozygous at the involved gene or genes than in females that are homozygous at that gene or those genes ... meaning that the Tsix gene overlaps the Xist gene and is transcribed on the opposite strand of DNA from the Xist gene. Tsix is ... The silencing of genes along the Xi occurs soon after coating by Xist RNA. Like Xist, the Tsix gene encodes a large RNA which ...
This gene is localized in the DSS (dosage-sensitive sex reversal) critical region. It is expressed in testis and placenta, and ... This gene is a member of the MAGEB gene family. The members of this family have their entire coding sequences located in the ... The promoters and first exons of the MAGEB genes show considerable variability, suggesting that the existence of this gene ... "Entrez Gene: MAGEB2 melanoma antigen family B, 2". Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the ...
Coordinate inter-genomic gene expression Duplicated genes often result in increased dosage of gene products. Doubled dosages ... The mechanism of retaining duplicated genes is poorly understood. It has been hypothesized that dosage balance may play a key ... First, the eliminated copy restores the normal gene dosage in the diploid organism. Second, the changes in chromosomal genetic ... The main goals of diploidization are: (1) To ensure proper gene dosage; and (2) to maintain stable cellular division processes ...
... the master switch gene controlling sex-determination system and dosage compensation. This protein is normally expressed in ... 2009). "xol-1, the master sex-switch gene in C. elegans, is a transcriptional target of the terminal sex-determining factor TRA ... Genes Dev. 17 (8): 977-90. doi:10.1101/gad.1082303. PMC 196039. PMID 12672694. This article incorporates text from the public ... males, where it promotes male development and prevents dosage compensation. The function of the Xol-1 protein is to act as a ...
Svenningsen SL, Tu KC, Bassler BL (2009). "Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae ... There are 5 different qrr genes (Qrr1-5) in V. harveyi; of these, qrr2, 3 and 4 are activated by LuxR. Lenz, DH; Mok KC; Lilley ... In Vibrio harveyi, Qrr binds and represses expression of the luxR mRNA transcript, a master regulator of quorum-sensing genes. ...
基因劑量(Gene dosage)會對人類的表現型產生龐大的影響,對於染色體中造成疾病的複寫、省略與分裂等現象的形成擁有一定的角色。例如唐氏症患者(21號染色體為三體)有較高的比率得到阿茲海默症,可能是因為與阿茲海默症有關的類澱粉前趨蛋白基因(位在21號 ... of which more than half do not overlap with known gene locations.. Claverie J. Fewer genes, more noncoding RNA.. Science. 2005 ... Watson, JD, Baker TA
The pills are created from sulfate salts and are sold in dosages of 100, 200, 333, and 400 mg of indinavir. It is normally used ... As a result, structural proteins, resulting from polypeptide products of gag and gag-pol genes, that are necessary for the HIV ... "Crixivan (Indinavir Sulfate): Side Effects, Interactions, Warning, Dosage & Uses". RxList. Retrieved 2018-11-08.. ...
These gene candidates include certain variations in tumor necrosis factor-alpha (TNF-alpha), IL-1 alpha, and CYP1A1 genes, ... with one study finding that a high dosage reduced inflammatory acne lesions by 73%.[114][115] However, spironolactone and ... Genes[edit]. Acne appears to be strongly inherited; genetics explain 81% of the variation in the population.[15] Studies ... among others.[19] The 308 G/A single nucleotide polymorphism variation in the gene for TNF is associated with an increased risk ...
The HLA genes fall in two categories (Type I and Type II). In general, mismatches of the Type-I genes (i.e. HLA-A, HLA-B, or ... and also serves as a signal to establish an appropriate dosage level for sustained treatment with low levels of ... as members of the same ethnic group are more likely to have matching genes, including the genes for HLA.[24] ... A mismatch of an HLA Type II gene (i.e. HLA-DR, or HLA-DQB1) increases the risk of graft-versus-host disease. In addition, a ...
With the PIN of the device, the scientist could wirelessly control the dosage of the insulin.[71] Anand Raghunathan, a ... Medical laboratory equipment automates or helps analyze blood, urine, genes, and dissolved gases in the blood. ...
... which is dangerous as the required dosage of lithium to treat bipolar disorder is only slightly lower than the toxic dosage.[ ... L. Brown, Theodore; LeMay, Jr., H. Eugene; Bursten, Bruce E.; Burdge, Julia R. (2003). Chemistry: The Central Science (8th ed ...
ref,{{cite journal,author=Lawrence DM,first=,date=May 2009,title=Gene studies shed light on rhinovirus diversity,url=,journal= ... Involved during an Episode of Common Colds-Practical Advice on Dosages and on the Time to Take These Nutrients/Botanicals in ... more research is needed to determine the optimal dosage, zinc formulation and duration of treatment before a general ...
Barbiturates showed some hydrolytic problems in regard to formulation of liquid dosage forms. The difficulty is -OH catalyzed ... "Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A ... Several efficient benzodiazepines offer choices about dosage form, length of action, metabolic interaction and safety. ...
Wormser, Gary P.; Dattwyler, Raymond J.; Shapiro, Eugene D.; Halperin, John J.; Steere, Allen C.; Klempner, Mark S.; Krause, ... and determine dosage are insufficient because they focus on TSH levels as an indicator of thyroid function and miss a large ...
The role of genes and environment in the etiology of PCOS. Endocrine. 2006, 30 (1): 19-26. PMID 17185788. doi:10.1385/ENDO:30:1 ... Elevated insulin levels have been helpful to predict response to medication and may indicate women needing higher dosages of ... Lin, Eugene C, 编. Imaging in Polycystic Ovary Disease. eMedicine. eMedicine. 20 April 2011 [19 November 2011].. ... Mutations in the genes encoding 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause ...
"Gene-culture coevolution between cattle milk protein genes and human lactase genes". Nature Genetics. 35 (4): 311-3. doi: ... Lactose-sensitive individuals can experiment with both timing and dosage to fit their particular needs. ... The LCT gene provides the instructions for making lactase. The specific DNA sequence in the MCM6 gene helps control whether the ... some humans developed a mutation in the MCM6 gene that keeps the LCT gene turned on even after breast feeding is stopped.[20] ...
Thus only by increasing dosage of the drug will provide the same satisfaction, making it dangerous for the user.[11] ... theory of natural selection in which successful organisms are more likely to prosper and survive to pass on their genes to the ...
Increasingly higher dosages will result in higher toxicity, resembling vitamin A toxicity. Adverse effects include:[23] ... schizophrenia and the retinoid cascade have been linked to the same gene loci;[47] and retinoid dysfunction causes congenital ... Risk factors for skeletal effects include older age, greater dosage and longer course of treatment. Most bone changes cause no ... Sehgal VN, Srivastava G, Sardana K (June 2006). "Isotretinoin--unapproved indications/uses and dosage: a physician's reference ...
Erowid Nicotine Vault : Dosage *↑ Guillem K, Vouillac C, Azar MR, et al. (september 2005). "Monoamine oxidase inhibition ... 2004). "Evidence of association between smoking and alpha7 nicotinic receptor subunit gene in schizophrenia patients". ...
One study suggested that this was possible through the up-regulation of PTEN gene expression in those breast cancer cells.[11] ... It operates as a photosensitizing drug that is as effective or, with high enough dosage, more effective than 8-methoxypsoralen ... the dosage, and the humidity, but the effects may be inconsistent.[7] ...
Prior to the invention of the CT, physicians and physicists had limited knowledge about the true radiation dosage delivered to ...
Homologs of the recA gene, including rad51, play a key role in homologous recombinational repair of DNA during meiosis. A rad51 ... However, even in the case of potatoes, while solanine poisoning resulting from dosages several times normal human consumption ... The C.M. Rick Tomato Genetics Resource Center at UC Davis is a gene bank of wild relatives, monogenic mutants and miscellaneous ... and bananas share the same characteristics and genes, researchers stated the published genome could help to improve food ...
It can be performed in various dosage forms such as pills, tablets, or capsules. The drug may contain a single or multiple ... gene therapy, monoclonal antibodies and cell therapy (for instance, stem-cell therapies). Other ways to classify medicines are ... Medical errors include overprescription and polypharmacy, misprescription, contraindication and lack of detail in dosage and ... they should therefore be available at all times in adequate amounts and in appropriate dosage forms, at a price the community ...
Its use is now restricted to the relief of nausea and vomiting and the dosage and duration of use have been reduced. It should ... the voltage-gated potassium channel KCNH2 gene (hERG/Kv11.1), and the α1D-adrenoceptor ADRA1D gene.[58] ... To induce lactation, domperidone is used at a dosage of 10 to 20 mg 3 or 4 times per day by mouth.[30] Effects may be seen ... Rathbone, Michael J.; Hadgraft, Jonathan; Roberts, Michael S. (2002). "The Zydis Oral Fast-Dissolving Dosage Form". Modified- ...
... the dosage must be higher than for other methods of administration.[5][6][14] ... the gene for aromatic amino acid decarboxylase (AADC), the major enzyme involved in the synthesis of the trace amines, is ...
Standardization of purity and dosage is not mandated in the United States, but even products made to the same specification may ... Phytochemical researcher Varro Eugene Tyler described paraherbalism as "faulty or inferior herbalism based on pseudoscience", ... few high-quality clinical trials and standards for purity or dosage exist.[2] The scope of herbal medicine is sometimes ...
About one in 3000 white North Americans is homozygous (i.e. has two copies of the abnormal gene) for the most common atypical ... Other issues may occur because of varying individual tolerance to procaine dosage. Nervousness and dizziness can arise from the ...
Strong evidence shows that the genes encoding the GluN2 subunits in vertebrates have undergone at least two rounds of gene ... in addition to their unique effects at elevated dosages such as dissociation. When certain NMDA receptor antagonists are given ... Homozygous disruption of the gene for GluN2B in mice causes perinatal lethality, whereas disruption of the GluN2A gene produces ... and two GluN3 subunit encoding genes, and each gene may produce more than one splice variant. ...
The term rheology was coined by Eugene C. Bingham, a professor at Lafayette College, in 1920, from a suggestion by a colleague ... Study of flow properties of liquids is important for pharmacists working in the manufacture of several dosage forms, such as ...
... genes that control the growth rate of cells) and tumor suppressor genes (genes that help to prevent cancer), which gives cancer ... Dosage[edit]. Dose response relationship of cell killing by chemotherapeutic drugs on normal and cancer cells. At high doses ... Upregulation of these genes can overcome the DNA damage and prevent the induction of apoptosis. Mutations in genes that produce ... With more copies of the gene, the drug can not prevent all expression of the gene and therefore the cell can restore its ...
Specific genes used for this are genes for barring and wing feather growth. Crosses of this sort create what are sold as Black ... parental genome dosage and hybridity contributions to heterosis in Arabidopsis thaliana". The New Phytologist. 209 (2): 590-599 ... Fewer genes are under-expressed in the homozygous individual. Gene expression in the offspring is equal to the expression of ... Over-expression of certain genes in the heterozygous offspring. (The size of the circle depicts the expression level of gene A) ...
Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (January 2005). "Meta-analysis: high-dosage vitamin E ... Brigelius-Flohé R, Davies KJ (July 2007). "Is vitamin E an antioxidant, a regulator of signal transduction and gene expression ... the urate oxidase gene is nonfunctional, so that UA is not further broken down.[87][88] The evolutionary reasons for this loss ... gene structures, evolution, and expression". Free Radical Biology & Medicine. 33 (3): 337-49. doi:10.1016/S0891-5849(02)00905-X ...
Certain progestins such as medroxyprogesterone acetate (MPA) and megestrol acetate (MGA) are used at very high dosages as a ... Other than genetically-stimulated appetite abnormalities, there are physiological ones that do not require genes for activation ...
Optimal dosages for melatonin supplementation therapy in older adults: a systematic review of current literature. 2014. ... Lincoln GA, Andersson H, Loudon A (October 2003). "Clock genes in calendar cells as the basis of annual timekeeping in mammals ... "Melatonin: Side Effects, Uses, Dosage (Kids/Adults)". Drugs.com. Retrieved 9 January 2019.. ... "Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the ...
CALUX, or Chemical Activated Luciferase gene eXpression is a novel high-throughput screening bioassay. In comparison to HRGC-MS ... both in the scope of the biological systems affected and in the range of dosage needed to bring these about.[2][3] Acute ... This receptor is a transcription factor which is involved in expression of many genes. TCDD binding to the AH receptor induces ...
The previous test of the dosage hypothesis of gene duplication assumes that if halving the gene dosage is deleterious ( ... The dosage effect refers to an insufficient amount of gene product when one allele of a gene is deleted, whereas the dosage ... the gene dosage hypothesis), because haploinsufficient genes were reported to have more paralogs than haplosufficient genes in ... Genomic test of the gene dosage hypothesis in yeast:. One disadvantage of the above analysis is that haploinsufficient genes ...
Increased dosage of particular genes results in overproduction of specific gene products and thereby confers resistance to ... Targeted selection of recombinant clones through gene dosage effects. J Rine, W Hansen, E Hardeman, and R W Davis ... Targeted selection of recombinant clones through gene dosage effects Message Subject (Your Name) has sent you a message from ...
Transgenic and gene-knockout mice of individual genes are used to investigate the consequences of functional gene-dosage of the ... To prove the gene-dosage effect hypothesis, we have cloned SOD1, the first chromosome 21 gene to be cloned, and demonstrated ... Trisomy 21 Gene-Dosage Effect. Down syndrome (DS), the phenotypic manifestation of trisomy 21, is one of the most common ... In so doing, we have proved the gene-dosage effect theory in trisomy 21 and opened the door into a new era in DS research. ...
D) Dosage compensation occurs when the expression of a structural gene does not change with its dosage. Dosage compensation ... 2007) Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance. Am J Hum Genet 81:252- ... A) A gene dosage effect occurs when the structural gene produces a proportional amount of product to its copy number. (B) There ... The gene dosage effects could potentially result simply from a change in concentration of a gene product in the cell, such as ...
Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry. Amy Lin, Christopher R. K. Ching, Ariana Vajdi, Daqiang Sun, Rachel K ... Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry. Amy Lin, Christopher R. K. Ching, Ariana Vajdi, Daqiang Sun, Rachel K ... Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry. Amy Lin, Christopher R. K. Ching, Ariana Vajdi, Daqiang Sun, Rachel K ... Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry Message Subject (Your Name) has forwarded a page to you from Journal ...
Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans.. Tissenbaum HA1, Guarente L. ... Yeast longevity gene goes public. [Nature. 2001]. *Regulation of Caenorhabditis elegans lifespan by sir-2.1 transgenes. [Nature ... Here we report that a duplication containing sir-2.1-the C. elegans gene most homologous to yeast SIR2-confers a lifespan that ... In yeast, the SIR2 gene determines the lifespan of mother cells, and adding an extra copy of SIR2 extends lifespan. Sir2 ...
... dosage, drug interactions, warnings, patient labeling, reviews, and related medications including drug comparison and health ... R-Gene 10 (Arginine Hydrochloride Injection) may treat, side effects, ... DOSAGE AND ADMINISTRATION. Adult Dosage. The recommended adult dose is 30 g arginine hydrochloride (300 mL of R-Gene 10) ... Pediatric Dosage. The recommended pediatric dose is 0.5 g/kg arginine hydrochloride (5 mL/kg of R-Gene 10) administered by ...
... the study of how a patients genes can affect drug reaction and dosage. ... Researchers Identify Two Genes Linked to Inflammatory Bowel Disease. Researchers have identified two genes linked to ... Genes on the Y Chromosome Prove Essential for Survival of Men. The human Y chromosome has over the course of millions of years ... the study of how a patients genes can affect drug reaction and dosage. ...
... Trieu M., Ma A., Eng S.R., ... Conversely, transgenic overexpression of Brn3a in the trigeminal ganglion suppresses the expression of the endogenous gene. ... demonstrating that autoregulation can compensate for the loss of one allele by increasing transcription of the remaining gene ...
... "mass action of genes hypothesis". Our results indicate that subtle changes in gene dosage across a chromosome can have ... The role of dosage sensitive genes in aneuploid phenotypes. Author(s). Bonney, Megan Ellis ... A central question is whether aneuploid phenotypes are the consequence of copy number changes of a few especially harmful genes ... that may be present on the extra chromosome, or are caused by copy number alterations of many genes that confer no observable ...
Gene dosage is the number of copies of a particular gene present in a genome. Gene dosage is known to be related to the amount ... These slight gene dosage differences are responsible for variation in gene expression depending on the position on the ... Nonetheless, changes in gene dosage (copy number variations) due to gene insertions or deletions can have significant ... The bacterial chromosome is present only in one copy per cell, but there can still be variation in gene dosage due to DNA ...
Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300.. Yao ... Thus, mouse development is exquisitely sensitive to the overall gene dosage of p300 and cbp. Our results provide genetic ... We have generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, ...
Dosage balance has been proposed to be a key issue of determining gene expression phenotype. Gene deletion or overexpression of ... Highly dosage sensitive genes encode proteins which are vulnerable to water attack. They are subject to tight post- ... This thesis uses a protein structure analysis protocol to explore the molecular basis of gene dosage sensitivity, and studies ... The strength of transcriptional co-regulation of interacting partners is supposed to reflect gene dosage sensitivity. Although ...
We show that gene dosage variation at specific chromosomal locations and also gene dosage balance at a global genomic scale are ... which can create complex phenotypic trait variation through effects on gene expression. For example, gene dosage variation has ... A comprehensive genomic scan reveals gene dosage balance impacts on quantitative traits in Populus trees . Proceedings of the ... Here we systematically explored the effect of induced gene dosage variation on quantitative trait variation in Populus. ...
... Hong-Qiang Liu,1 Chang ... "Influence of Two Common Polymorphisms in the EPHX1 Gene on Warfarin Maintenance Dosage: A Meta-Analysis," BioMed Research ...
Dosage Thresholds for AAV2 and AAV8 Photoreceptor Gene Therapy in Monkey. By Luk H. Vandenberghe, Peter Bell, Albert M. Maguire ... Dosage Thresholds for AAV2 and AAV8 Photoreceptor Gene Therapy in Monkey. By Luk H. Vandenberghe, Peter Bell, Albert M. Maguire ... Dosage Thresholds for AAV2 and AAV8 Photoreceptor Gene Therapy in Monkey Message Subject. (Your Name) has forwarded a page to ... A Correction to the Research Article Titled: "Dosage Thresholds for AAV2 and AAV8 Photoreceptor Gene Therapy in Monkey" by L. H ...
... and many X-linked genes did not become subject to XCI. We reconstructed gene-by-gene dosage sensitivities on the ancestral ... Analogous heterogeneities among avian Z-linked genes predicted either the retention of a W homolog or gene-specific dosage ... Conserved microRNA targeting reveals preexisting gene dosage sensitivities that shaped amniote sex chromosome evolution. Author ... "Conserved microRNA Targeting Reveals Preexisting Gene Dosage Sensitivities That Shaped Amniote Sex Chromosome Evolution." ...
Zygotically transcribed genes Sex Determination and Dosage Compensation Genes. A simplified model for sex determination in the ... Chromosome topology guides the Drosophila Dosage Compensation Complex for target gene activation. X chromosome dosage ... Dosage compensation of neo-X genes is advantageous because ~40% of homologous neo-Y genes are pseudogenized; however, because ... Dosage compensation mechanisms in flies and mammals lead to opposite outcomes; namely, gene activation versus gene repression. ...
... do not have an identifiable mutation of the MECP2 gene. We hypothesized that larger deletions arising from a deletion prone ... Large deletions of the MECP2 gene detected by gene dosage analysis in patients with Rett syndrome Hum Mutat. 2004 Mar;23(3):234 ... do not have an identifiable mutation of the MECP2 gene. We hypothesized that larger deletions arising from a deletion prone ...
At least 11 Pc group genes have been described and there may be up to 40; all are required for normal regulation of homeotic ... genes, but as a group, their phenotypes are rather diverse. It … ... group of genes are required for maintenance of cell determination in Drosophila melanogaster. ... Genetic interactions and dosage effects of Polycomb group genes of Drosophila Mol Gen Genet. 1995 Feb 6;246(3):291-300. doi: ...
The Association of Warfarin Dosage and Plasma Enantiomer Concentration With the Gene Polymorphisms of CYP and VKOR ... The Association of Warfarin Dosage and Plasma Enantiomer Concentration With the Gene Polymorphisms of CYP and VKOR. * ... Patients require different dosage to achieve the target therapeutic anticoagulation. Optimal dosage and bleeding complication ... In our study we will first identify the polymorphism patterns of these two genes in normal population. Then, we will try to ...
... a gene dosage requirement for Hand2 in SG-specific gene expression in vivo and that Hand1 is directly sensitive to Hand2-dosage ... of wild-type dosage. We reasoned that, if Hand1 does indeed contribute to the overall Hand factor gene dosage requirement, this ... 4I,J). Together, these data show that the Hand1 SG enhancer is regulated by Hand2 in a gene dosage-dependent manner. ... However, we also show that these E-box elements are uniquely responsive to Hand2 gene dosage, indicating that Hand1 cannot ...
Diabetic Nephropathy Induced by Increased Ace Gene Dosage Is Associated with High Renal Levels of Angiotensin (1-7) and ... ACE gene polymorphisms might also account for these discrepancies since ACE gene variance is associated with increased risk of ... or insert an extra copy of a gene adjacent to the existing gene (knock in). ... ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight. Physiol Genomics. 2005;20(2):173-82 ...
We identified 37 genes that we will refer to as dosage mutator (dMutator) genes, the majority of which are involved in DNA ... Dosage Mutator Genes in Saccharomyces cerevisiae: A Novel Mutator Mode-of-Action of the Mph1 DNA Helicase. *J. Sidney Ang*,1, ... Dosage mutator genes affect DNA metabolism. It is clear how the LOF or the ROF of a cellular protein may lead to a phenotype ... Dosage mutator screens and confirmations. We used synthetic genetic array (SGA) technology to introduce a wild type CAN1 gene ...
... via gene dosage effects) are directly linked to the growth speed of the bacteria. Gene dosage effects could, therefore, be seen ... genes that are constitutively expressed and where gene dosage plays a major role in affecting transcript levels and (ii) genes ... It is not clear though to what extent any other genes are affected by gene dosage. The tuf genes, present in two separate ... If a gene were to be moved to a new location associated with a decrease in gene dosage, it should be possible to adjust ...
Gli2 gene dosage and gene-environment interaction illuminate the etiological complexity of holoprosencephaly ... Gli2 gene dosage and gene-environment interaction illuminate the etiological complexity of holoprosencephaly ... Gli2 gene dosage and gene-environment interaction illuminate the etiological complexity of holoprosencephaly ... Gli2 gene dosage and gene-environment interaction illuminate the etiological complexity of holoprosencephaly ...
... our study suggests that the nephron reduction can be considered a suitable model to study ACKD and that dosage of genes ... our study suggests that the nephron reduction can be considered a suitable model to study ACKD and that dosage of genes ... Cystic gene dosage influences kidney lesions after nephron reduction. Nephron Clinical Practice, 129:42-51. ... Cysts can be acquired, or they may appear during development or in postnatal life due to specific gene defects and lead to ...
"All genes", "Expressed genes", "Genes subject to XCI (removal of PAR genes)" and "Dosage sensitive genes" (Figure 4). "All ... ", "Expressed genes", "Genes subject to XCI (removal of genes in PAR)" and "Dosage sensitive genes". Red dotted line: the ... A total of 7,166 genes were expressed among all tissues and defined as "dosage sensitive" genes (Sangrithi et al. 2017). Genes ... Taken together, our analysis of the four gene categories suggests that dosage regulation is highly related to gene functions. ...
Macromolecular crowding links ribosomal protein gene dosage to growth rate in Vibrio cholerae. BMC Biology. 2020;2020(18). 43. ... Macromolecular crowding links ribosomal protein gene dosage to growth rate in Vibrio cholerae. / Soler-Bistue, A.; Aguilar- ... Macromolecular crowding links ribosomal protein gene dosage to growth rate in Vibrio choleraeForlagets udgivne version, 2,22 MB ... CONCLUSIONS: The genomic location of RP genes ensures its optimal dosage. However, besides of its essential function in ...
  • 2011), Genetics: from genes to genomes (4th ed. (wikipedia.org)
  • A common feature of bacterial genomes is that the organization of genes on the chromosome is often highly skewed with respect to location relative to the origin of replication. (asm.org)
  • While genome sequence analyses provide overwhelming evidence that gene location bias is an important feature of bacterial genomes, they leave unanswered questions concerning the magnitude and nature of the selective forces underlying this situation. (asm.org)
  • Seed development is sensitive to parental dosage, with excess maternal or paternal genomes creating reciprocal phenotypes. (plantcell.org)
  • Molecular genetics of charcot-marie-tooth disease: from genes to genomes. (semanticscholar.org)
  • Many genomes display extensive gene duplication, which may result from either small-scale duplications or from duplication of the whole genome. (biomedcentral.com)
  • However, significant gene copy number variation exists across genomes 1;therefore, coordinate regulation is required to equalize transcription levels 2 3. (grantome.com)
  • We summarize, in this review, the evidence that genomic balance influences gene expression, quantitative traits, dosage compensation, aneuploid syndromes, population dynamics of copy number variants and differential evolutionary fate of genes after partial or whole-genome duplication. (pnas.org)
  • Direct autoregulation and gene dosage compensation by POU-domain transcription factor Brn3a. (uniprot.org)
  • Analogous heterogeneities among avian Z-linked genes predicted either the retention of a W homolog or gene-specific dosage compensation following W gene decay. (mit.edu)
  • Methylation and expression analyses of Pallister-Killian syndrome reveal partial dosage compensation of tetrasomy 12p and hypomethylation of gene-poor regions on 12p. (lu.se)
  • Thus, partial dosage compensation occurs in cells with i(12p). (lu.se)
  • Differences between the development of mammals and fish include genomic imprinting and dosage compensation. (biomedcentral.com)
  • The dosage-compensation model, on the other hand, invokes a negative selection pressure to retain the function and expression levels of both copies in order to preserve the correct stoichiometry - the appropriate amounts or activity of the proteins in relation to each other or other proteins. (biomedcentral.com)
  • Selection for redundancy, like that for dosage compensation, is characterized by negative selection. (biomedcentral.com)
  • In many organisms, dosage compensation has thus evolved to equalize sex-linked gene expression in males and females. (biomedcentral.com)
  • While otherwise widespread in systems with heteromorphic sex chromosomes, the case of dosage compensation in birds (males ZZ, females ZW) remains an unsolved enigma. (biomedcentral.com)
  • The distribution of male-to-female fold-change values for Z chromosome genes is wide and has a mean of 1.4-1.6, which is consistent with absence of dosage compensation and sex-specific feedback regulation of gene expression at individual loci. (biomedcentral.com)
  • Intriguingly, without global dosage compensation, the female chicken has significantly lower expression levels of Z-linked compared to autosomal genes, which is not the case in male birds. (biomedcentral.com)
  • Importantly, this report, together with a recent study of sex-biased expression in somatic tissue of chicken, demonstrates the first example of an organism with a lack of global dosage compensation, providing an unexpected case of a viable system with large-scale imbalance in gene expression between sexes. (biomedcentral.com)
  • However, it is well known that organisms have evolved various mechanisms for equilibrating the expression of X-linked genes in males and females (dosage compensation), including X chromosome inactivation in mammals, up-regulation of gene expression on the single X chromosome of Drosophila males and down-regulation of gene expression of both X chromosomes of Caenorhabditis elegans hermaphrodites [ 16 , 17 ]. (biomedcentral.com)
  • With the exception of individual genes that escape dosage compensation [ 18 ], sex-linked gene dose should therefore not be expected to lead to overall differences in expression levels between males and females. (biomedcentral.com)
  • Dosage compensation is one of the best model systems for studying this process because all of the genes on a single chromosome are specifically identified and co-regulated. (grantome.com)
  • The objective of this application is to understand how dosage compensation in Drosophila is established, the critical first step in the regulatory process. (grantome.com)
  • The Drosophila Male Specific Lethal (MSL) complex is central to dosage compensation;it first identifies the X chromosome using a combination of cis-acting DNA sequences 6 and co-transcriptional recruitment by its roX (RNA on X) non-coding RNA components7 and then spreads into the bodies of active genes 8. (grantome.com)
  • We used an innovative genetic screen for new regulators of dosage compensation that function in both males and females and thereby identified the essential CLAMP zinc-finger protein. (grantome.com)
  • Dosage compensation mechanisms equalize the level of X chromosome expression between sexes. (desdaughter.com)
  • The relationship between X chromosome dosage compensation and sex-biased gene expression remains largely unexplored. (desdaughter.com)
  • In early embryogenesis, when dosage compensation is not yet fully active, X chromosome dose drives the hermaphrodite-biased expression of many X-linked genes, including several genes that were shown to be responsible for hermaphrodite fate. (desdaughter.com)
  • A similar effect is seen in the C. elegans germline, where X chromosome dose contributes to higher hermaphrodite X expression, suggesting that lack of dosage compensation in the germline may have a role in supporting higher expression of X chromosomal genes with female-biased functions in the gonad. (desdaughter.com)
  • In the soma, dosage compensation effectively balances X expression between the sexes. (desdaughter.com)
  • These results suggest that lack of dosage compensation in different tissues and developmental stages allow X chromosome copy number to contribute to sex-biased gene expression and function. (desdaughter.com)
  • Interestingly, the Z chromosome is not enriched for sex-biased genes, and seems to in fact have a mechanism of dosage compensation that leads to equal expression in males and in females. (ist.ac.at)
  • Both of these patterns are contrary to most ZW systems studied so far, making A. franciscana an excellent model for investigating the interplay between the evolution of sexual dimorphism and dosage compensation, as well as Z chromosome evolution in general. (ist.ac.at)
  • Huylmans AK, Toups MA, Macon A, Gammerdinger WJ, Vicoso B. Sex-biased gene expression and dosage compensation on the Artemia franciscana Z-chromosome. (ist.ac.at)
  • Supplementary data for "Sex-biased gene expression and dosage compensation on the Artemia franciscana Z-chromosome" (Huylman, Toups et al. (ist.ac.at)
  • Dosage sensitivity would predict that this should be compensated, and indeed elaborate mechanisms exist to mitigate this imbalance-it was recently discovered that in eukaryotes histone-mediated dosage compensation mechanisms dampen expression from early-replicating loci during cell replication, thus rebalancing the gene products with those from late-replicating loci [ 11 , 12 ]. (biomedcentral.com)
  • The C. elegans dosage compensation complex (DCC) reduces transcript levels from each of the two hermaphrodite X chromosomes to equalize X-linked gene expression to that of XO males. (nyu.edu)
  • Ercan, S & Lieb, JD 2009, ' C. elegans dosage compensation: A window into mechanisms of domain-scale gene regulation ', Chromosome Research , vol. 17, no. 2, pp. 215-227. (nyu.edu)
  • Many organisms have a global mechanism for dosage compensation (DC) operating along the entire male X chromosome, which equalizes gene expression on the male X with that on the two Xs in females and/or on autosomes. (edu.sa)
  • Nozawa M, Ikeo K, Gojobori T (2018) Gene-by-gene or localized dosage compensation on the neo-X chromosome in Drosophila miranda. (edu.sa)
  • Under the dosage-compensation model (bottom left), all interactions are retained. (beds.ac.uk)
  • Dosage compensation is the process by which organisms equalize the expression of genes between members of different biological sexes. (wikipedia.org)
  • Some lineages have evolved dosage compensation, an epigenetic mechanism which restores expression of X or Z specific genes in the heterogametic sex to the same levels observed in the ancestor prior to the evolution of the sex chromosome. (wikipedia.org)
  • The third documented type of gene dose regulatory mechanism is incomplete compensation without balance (sometimes referred to as incomplete or partial dosage compensation). (wikipedia.org)
  • There are three main mechanisms of achieving dosage compensation which are widely documented in the literature and which are common to most species. (wikipedia.org)
  • A summary of these forms of dosage compensation is illustrated below. (wikipedia.org)
  • However, there are also other less common forms of dosage compensation, which are not as widely researched and are sometimes specific to only one species (as observed in certain bird and monotreme species). (wikipedia.org)
  • The evidence for this mechanism of dosage compensation was discovered prior to scientists' understanding of what its implications were. (wikipedia.org)
  • It was recently proposed that the fixation of duplicate genes is frequently driven by positive selection for increased gene dosage ( i.e ., the gene dosage hypothesis), because haploinsufficient genes were reported to have more paralogs than haplosufficient genes in the human genome. (genetics.org)
  • Yeast haploinsufficient genes do exhibit enhanced retention after whole-genome duplication compared to haplosufficient genes if they encode members of stable protein complexes, but the same phenomenon is absent if the genes do not encode protein complex members, suggesting that the dosage balance effect rather than the dosage effect is the underlying cause of the phenomenon. (genetics.org)
  • GENE duplication is the primary source of new genes ( O hno 1970 ) and duplicate genes are prevalent in virtually every sequenced genome in every domain of life ( Z hang 2003 ). (genetics.org)
  • The likelihood of gene duplication during evolution is measured by gene duplicability, which is the product of the rate of mutation producing duplicate genes and the probability that the duplicates are fixed and retained in the genome ( H e and Z hang 2005a ). (genetics.org)
  • In closing a circle opened 20 years earlier by sequencing the first chromosome 21 gene, we participated in the Human Genome Chromosome 21 sequencing consortium, which generated the complete sequence of the chromosome ( Figure1 at left. (weizmann.ac.il)
  • Gene dosage is the number of copies of a particular gene present in a genome. (wikipedia.org)
  • Genome-wide analyses of human copy number variation indicate that these heterogeneities consisted of sensitivity to both increases and decreases in dosage. (mit.edu)
  • Genome instability arises either due to defects in genes that cause an increased mutation rate (mutator phenotype), or defects in genes that cause chromosome instability (CIN). (genetics.org)
  • To extend the catalog of genome instability genes, we systematically explored the effects of gene overexpression on mutation rate, using a forward-mutation screen in budding yeast. (genetics.org)
  • Genome instability is an enabling characteristic of cancer, by increasing the likelihood of accumulating mutations in multiple driver genes ( Hanahan and Weinberg 2011 ). (genetics.org)
  • In Saccharomyces cerevisiae, the genes coding for the ribosomal protein L2 are present in two copies per haploid genome. (asm.org)
  • The high retention of duplicate genes in the genome of Paramecium tetraurelia has led to the hypothesis that most of the retained genes have persisted because of constraints due to gene dosage. (biomedcentral.com)
  • What determines whether both copies of a duplicate gene are retained in the genome, and their subsequent evolutionary fate, is still a matter of debate. (biomedcentral.com)
  • When duplication of a gene, or genome, occurs in an individual organism, it will only become part of the species genome if it becomes 'fixed' in the population (that is, becomes part of the genome of all members of the population). (biomedcentral.com)
  • In line with theoretical predictions for the probability of fixation of sexually antagonistic mutations [ 7 ], it has been observed that genes with sex-biased expression are non-randomly distributed in the genome. (biomedcentral.com)
  • The Clinical Genome Resource (ClinGen) consortium is curating genes and regions of the genome to assess whether there is evidence to support that these genes/regions are dosage sensitive and should be targeted on a cytogenomic array. (clinicalgenome.org)
  • We performed genome-phenome correlation among 80 symptomatic HCM patients, 35 asymptomatic carriers and 35 non-carriers, using an 18-gene clinical diagnostic HCM panel. (cdc.gov)
  • When gene expression in humans and chimpanzees was compared for the first time in 2005 and when the first chromosomes of the chimpanzee genome were first sequenced, I was a little disappointed . (epilepsygenetics.net)
  • We usually shy away from segmental duplications and highly copy number variable genes as these parts of the human genome appear to be unpredictable and hard to analyze. (epilepsygenetics.net)
  • The study by Davis and collaborators suggests that the highly dosage variable parts of the human genome might be relevant targets for various neurodevelopmental disorders including epilepsy . (epilepsygenetics.net)
  • For a subset of genes in our genome a change in gene dosage, by duplication or deletion, causes a phenotypic effect. (biomedcentral.com)
  • However, for a significant fraction of the genome alteration of gene dosage has deleterious effects. (biomedcentral.com)
  • Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. (nature.com)
  • Possible outcomes for gene retention after whole-genome duplication. (beds.ac.uk)
  • Our results help clarify the relation between CNV dosage and gene expression in the D. melanogaster genome. (omicsdi.org)
  • K ondrashov and K oonin (2004) conducted a genomic test of the gene dosage hypothesis. (genetics.org)
  • The work by Birchler and Newton ( 11 ) suggested that a perturbation of stoichiometric relationships of regulatory gene products was a contributor to the effects of genomic imbalance and played a role in these transacting dosage effects on gene expression. (pnas.org)
  • This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. (jneurosci.org)
  • We show that gene dosage variation at specific chromosomal locations and also gene dosage balance at a global genomic scale are both major determinants of quantitative trait variation in a plant species. (usda.gov)
  • BACKGROUND: In fast-growing bacteria, the genomic location of ribosomal protein (RP) genes is biased towards the replication origin (oriC). (ruc.dk)
  • Relocation of s10-spc-alpha locus (S10), which codes for most of the RP, to ectopic genomic positions shows that its relative distance to the oriC correlates to a reduction on its dosage, its expression, and bacterial growth rate. (ruc.dk)
  • CONCLUSIONS: The genomic location of RP genes ensures its optimal dosage. (ruc.dk)
  • abstract = "In fast-growing bacteria, the genomic location of ribosomal protein (RP) genes is biased towards the replication origin (oriC). (ruc.dk)
  • Genomic Selection with Allele Dosage in Panicum maximum Jacq. (g3journal.org)
  • In this work, we provide bioinformatic and modeling guidelines to consider tetraploid dosage and observed that genomic selection may lead to additional gains in recurrent selection program of P. maximum . (g3journal.org)
  • Southern blot hybridization of EcoRI-digested genomic DNA from S. aureus T991 with a 883-bp DNA probe containing domain V of the S. aureus 23S rRNA gene revealed that T991 carries five copies of this gene (data not shown). (asm.org)
  • Genomic imprinting results in the expression of a subset of genes according to parental origin. (asm.org)
  • Finally, using allele-specific transcription data, we present evidence for a transcriptional buffering system that increases the expression of maternal alleles and represses paternal alleles in response to excess paternal genomic dosage. (plantcell.org)
  • Given the unusual mechanism and the strong evolutionary framework of DUF1220 dosage, this is an interesting finding that highlights a class of genomic variation that has not been analyzed in detail yet. (epilepsygenetics.net)
  • However, the previous analysis incorrectly assumed that the presence of dominant abnormal alleles of a human gene means that the gene is haploinsufficient, ignoring the fact that many dominant abnormal alleles arise from gain-of-function mutations. (genetics.org)
  • Most duplications of Pc group genes neither exhibit anterior transformations nor suppress the extra sex comb phenotype of Pc group mutations, suggesting that not all Pc group genes behave as predicted by the mass-action model. (nih.gov)
  • Flies with increasing doses of esc+ exhibit anterior transformations, but these are not enhanced by mutations in trithorax group genes. (nih.gov)
  • Here, we demonstrate that mutations in Gli2, which encodes a Hedgehog pathway transcription factor, can cause or predispose to HPE depending upon gene dosage. (biologists.org)
  • Acquisition of homozygous activating growth factor receptor mutations might accelerate cancer progression through a simple gene-dosage effect. (lu.se)
  • article{176cf1cc-a519-4061-bb23-e3fa53bb9f31, abstract = {Acquisition of homozygous activating growth factor receptor mutations might accelerate cancer progression through a simple gene-dosage effect. (lu.se)
  • Linezolid resistance in Staphylococcus aureus is typically associated with mutations in the 23S rRNA gene. (asm.org)
  • This study was aimed at (i) correlating the level of linezolid resistance in S. aureus with the presence of mutations in the different copies of the 23S rRNA gene, (ii) analyzing the stability of linezolid resistance, (iii) determining the fitness costs associated with linezolid resistance, and (iv) assessing the issue of cross-resistance to other protein synthesis inhibitors. (asm.org)
  • DNA sequence analysis demonstrated that S. aureus T991 does not contain any mutations in domain V of its five 23S rRNA gene copies. (asm.org)
  • To investigate whether BRG1 and BRM have overlapping functions during mouse embryogenesis, we performed double-heterozygous intercrosses using constitutive null mutations previously created by gene targeting. (deepdyve.com)
  • For this, three model systems are used within the lab: primary hippocampal neurons, Drosophila melanogaster and the mouse.Whereas early-on it was generally accepted that most genetic disorders were caused by gene deletions or loss-of function mutations, recently it has become clear that duplications can underlie (severe) genetic diseases as well. (kuleuven.be)
  • Spinal muscular atrophy (SMA) is a common inherited and fatal neuromuscular disease caused by deletions and/or mutations that lead to altered concentrations of proteins encoded by the survival motor neuron genes SMN1 and SMN2 . (aaccjnls.org)
  • The disease is caused by a loss of α-motor neurons in the spinal cord anterior horn cells and results from mutations in the survival motor neuron (SMN) genes. (aaccjnls.org)
  • Epidermal growth factor receptor (EGFR) mRNA expression and EGFR gene dosage by quantitative PCR in tumor samples obtained from patients with gefitinib-treated non-small cell lung cancer were analyzed in order to determine the association with treatment outcome, clinical, and biological features [EGFR copy number by fluorescent in situ hybridization (FISH), EGFR tyrosine kinase mutations, and EGFR protein expression]. (nih.gov)
  • To study this dosage effect, we characterized two PAX6 mutations in a family segregating aniridia and a milder syndrome consisting of congenital cataracts and late onset corneal dystrophy. (elsevier.com)
  • Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). (elsevier.com)
  • Over 1,500 gene mutations are known to cause hypertrophic cardiomyopathy (HCM). (cdc.gov)
  • Previous studies suggest that cardiac β-myosin heavy chain (MYH7) gene mutations are commonly associated with a more severe phenotype, compared to cardiac myosin binding protein-C (MYBPC3) gene mutations with milder phenotype, incomplete penetrance and later age of onset. (cdc.gov)
  • A total of 125 mutations were identified in 14 genes. (cdc.gov)
  • The strength of transcriptional co-regulation of interacting partners is supposed to reflect gene dosage sensitivity. (rice.edu)
  • Although many cases of dosage imbalance effects have been reported, the molecular attributes determining dosage sensitivity remain unknown. (rice.edu)
  • This thesis uses a protein structure analysis protocol to explore the molecular basis of gene dosage sensitivity, and studies the post-transcriptional regulation of dosage sensitive genes. (rice.edu)
  • Protein structure vulnerability may hence serves as a structure marker for dosage sensitivity. (rice.edu)
  • It turns out that structure vulnerability quantifies dosage sensitivity for both temporal phases (yeast) and tissue-specific (human) patterns of mRNA expression, determining the extent of co-expression similarity of binding partners. (rice.edu)
  • Preexisting heterogeneities in dosage sensitivity, manifesting as differences in the extent of miRNA-mediated repression, predicted either the retention of a Y homolog or the acquisition of XCI following Y gene decay. (mit.edu)
  • Our findings thus provide a more complete view of the role of dosage sensitivity in shaping the mammalian and avian sex chromosomes and reveal an important role for post-transcriptional regulatory sequences (miRNA target sites) in sex chromosome evolution. (mit.edu)
  • These findings prompt reconsideration of models for dosage sensitivity in endosperm. (plantcell.org)
  • Epidermal growth factor receptor messenger RNA expression, gene dosage, and gefitinib sensitivity in non-small cell lung cancer. (nih.gov)
  • PMID:21844811) that provides evidence for or against dosage sensitivity. (clinicalgenome.org)
  • We discuss how synergy between adaptive and innate immune responses can lead to autoimmunity, including aspects such as colocalization between receptor and ligand, the impact that methylation and other modifications have on the receptors' sensitivity to nucleic acids, and gene dosage of these receptors. (jimmunol.org)
  • Opposite effects on facial morphology due to gene dosage sensitivity. (ox.ac.uk)
  • This gene copy number sensitivity creates characteristic evolutionary constraints that can serve as a diagnostic to identify dosage-sensitive genes. (biomedcentral.com)
  • Various types of dosage sensitivity. (biomedcentral.com)
  • Dosage sensitivity can be due to any of several different mechanisms. (biomedcentral.com)
  • We find that both approaches can predict genes known to cause disease through changes in expression level, genes depleted of loss-of-function alleles in the general population, and genes permissive of copy number variants in the general population. (prolekare.cz)
  • In mice carrying two defective alleles of the corresponding Clc1 gene, chloride conductance (G(Cl)) is reduced to less than 10% of that of wild-type, and this causes hyperexcitability, the salient feature of the disease myotonia. (uni-bielefeld.de)
  • We also analyzed a subgroup of 40 patients who completed the maintenance phase of ALL treatment, and we found that patients carrying a TPMT gene variant allele required a significantly lower median cumulative dosage and median daily dosage of 6-MP than patients carrying wild type alleles. (biomedcentral.com)
  • METHODS: We acquired mutant Neurog3 reporter mice carrying 2, 1, or null Neurog3 alleles to study Neurog3 gene dosage effect by lineage tracing. (umassmed.edu)
  • This gene dosage hypothesis is supported by several case studies. (genetics.org)
  • In this work, we analyze the relationship between gene haploinsufficiency and gene duplicability in humans and yeast and discuss why the gene dosage hypothesis is unlikely to explain the fixations of most duplicate genes. (genetics.org)
  • Since the discovery in 1959 that the DS phenotype is caused by the trisomy of chromosome 21, the prevailing hypothesis was that DS pathology results from gene-dosage imbalance, in the sense that overproduction of some of the proteins encoded by chromosome 21 genes disturbs the metabolic balance required for proper development and normal function. (weizmann.ac.il)
  • To prove the gene-dosage effect hypothesis, we have cloned SOD1, the first chromosome 21 gene to be cloned, and demonstrated that extra copies of the gene produce in transgenic mice abnormalities similar to the anatomical and clinical symptoms observed in DS patients. (weizmann.ac.il)
  • This hypothesis is examined through the integration of gene expression, protein structure and interaction data sets. (rice.edu)
  • Ohno's hypothesis predicts that the expression of the single X chromosome in males needs compensatory upregulation to balance its dosage with that of the diploid autosomes. (g3journal.org)
  • The main hypothesis of this PhD was that gene dosage would play a major role in the development of antimonial resistance in the ISC. (uantwerpen.be)
  • A deficiency of singletons in recessive dosage-sensitive CNVs supports the hypothesis that most CNVs are subject to negative selection. (omicsdi.org)
  • A central question is whether aneuploid phenotypes are the consequence of copy number changes of a few especially harmful genes that may be present on the extra chromosome, or are caused by copy number alterations of many genes that confer no observable phenotype when varied individually. (mit.edu)
  • Gene deletion or overexpression of any component in a protein complex produces abnormal phenotypes. (rice.edu)
  • all are required for normal regulation of homeotic genes, but as a group, their phenotypes are rather diverse. (nih.gov)
  • We examined the phenotypes of adult flies heterozygous for every pairwise combination of Pc group genes in an attempt to subdivide the Pc group functionally. (nih.gov)
  • The systems biology approaches together pointed to novel aspects of KS disease phenotypes including perturbed Jak-STAT pathway, dysregulated genes important for disturbed immune system (IL4), energy balance (POMC and LEP) and erythropoietin signalling in KS. (dtu.dk)
  • Speakers and participants will describe genotype-phenotype links, the molecular mechanisms by which gene dosage results in the syndrome phenotypes, and potential for therapeutic intervention, thus providing a rich and unique learning environment. (nih.gov)
  • However, when the authors focus on more subtle phenotypes such as quantitative measures of social deficits, communicative impairments and repetitive behaviors, they find a linear association with DUF1220 dosage. (epilepsygenetics.net)
  • To study in mice the consequences of gene duplications, transgenic mice overexpressing these genes can be generated. (kuleuven.be)
  • We followed the diagnostic algorithm illustrated in [Figure 1] , to increase the diagnostic yield in patients in this group of disorders, but albeit is not limited to these disorders and is recommended for Mendelian disorders because the mutation spectrum of many genes remain understudied and deletions and duplications may represent a significant percentage of pathogenic changes. (jtggjournal.com)
  • For example, for genes amplified in segmental duplications , there was a strong focus on brain-expressed genes. (epilepsygenetics.net)
  • Gene dosage (deletions and duplications) affect the same neuroimaging measures in opposite directions (mirror effect). (nature.com)
  • Generally speaking, a duplicate gene may be fixed in a population by genetic drift or positive selection. (genetics.org)
  • Research in our lab addresses disease conditions in which genetic predisposition of individual chromosome 21 genes play a role. (weizmann.ac.il)
  • In eukaryotes, most genes found in the cell are expressed as autosomal genes (see autosome) and are found in two copies, alterations to this two-copy gene dosage is significantly associated with quantitative or qualitative phenotype traits and is linked to many genetic health problems such as those associated with spinal muscular atrophy and Down syndrome. (wikipedia.org)
  • Genetic decay of the Y led to X Chromosome inactivation (XCI) in females, but some Y-linked genes were retained during the course of sex chromosome evolution, and many X-linked genes did not become subject to XCI. (mit.edu)
  • We show genetic interactions among extra sex combs (esc) and Asx, Enhancer of Pc, Pcl, Enhancer of zeste E(z), and super sex combs and reassess the idea that most Pc group genes function independently of esc. (nih.gov)
  • However, only a short period of experimental evolution was required before the bacteria adapted to this EF-Tu starvation situation by acquiring genetic changes that increased expression levels from the translocated tufB gene, restoring growth rates. (asm.org)
  • This genetic predisposition is associated with a Gli2 dosage-dependent attenuation of Hedgehog ligand responsiveness at the cellular level. (biologists.org)
  • We then assess each gene's proximal noncoding region for phylogenetic conservation and intolerance to genetic variation in the human population, and tie these scores back to genes known to cause disease due to a gene dosage aberration. (prolekare.cz)
  • Because of the high incidence (at least 1 in 10 000 live births and a carrier frequency of 1 in 35 to 1 in 50) and severity of the disease, precise quantification of SMN1 and SMN2 gene copy numbers is essential for diagnosis and genetic counseling. (aaccjnls.org)
  • DNA was isolated from whole blood and genetic polymorphism in thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) coding genes were detected by polymorphism chain reaction-restriction fragment length (PCR-RFLP) assay. (biomedcentral.com)
  • Indeed, Sewell Wright argued that even the very phenomenon of genetic dominance is suggestive of a tolerance of gene dosage changes [ 4 ]. (biomedcentral.com)
  • Chromosomes are strands of DNA (the genetic material in the cell nucleus) that are made up of genes-the units of heredity. (clinicaltrials.gov)
  • Highly expressed genes are commonly located close to the origin of replication of bacterial chromosomes (OriC). (asm.org)
  • IMPORTANCE A feature of bacterial chromosomes is that highly expressed essential genes are usually located close to the origin of replication. (asm.org)
  • Another mechanism, X chromosome inactivation (XCI), the inactivation of one of the two X chromosomes in every cell of the female, balances the X chromosome gene dosage between males and females ( Lyon 1961 ). (g3journal.org)
  • The i(12p)-positive cells displayed global hypomethylation of gene-poor regions on 12p, a footprint previously associated with constitutional and acquired gains of whole chromosomes as well as with X-chromosome inactivation in females. (lu.se)
  • The contrasting dose of sex chromosomes in males and females potentially introduces a large-scale imbalance in levels of gene expression between sexes, and between sex chromosomes and autosomes. (biomedcentral.com)
  • Keep in mind that the COMT is just one of the 30,000 to 50,000 plus genes, which are spread out over 23 pairs of chromosomes in humans. (blogspot.com)
  • We therefore tested whether the up-regulation of X-linked genes depends on the status of their Y-linked homologs, using the young sex chromosomes, neo-X and neo-Y, in Drosophila miranda. (edu.sa)
  • In order to neutralize the large difference in gene dosage produced by differing numbers of sex chromosomes among the sexes, various evolutionary branches have acquired various methods to equalize gene expression among the sexes. (wikipedia.org)
  • Because sex chromosomes contain different numbers of genes, different species of organisms have developed different mechanisms to cope with this inequality. (wikipedia.org)
  • Different lineages have evolved different mechanisms to cope with the differences in gene copy numbers between the sexes that are observed on sex chromosomes. (wikipedia.org)
  • One logical way to equalize gene expression amongst males and females that follow a XX/XY sex differentiation scheme would be to decrease or altogether eliminate the expression of one of the X chromosomes in an XX, or female, homogametic individual, such that both males and females then express only one X chromosome. (wikipedia.org)
  • The concept of gene dosage balance arose in the early days of the field of genetics, with the work by Blakeslee et al. (pnas.org)
  • A recent paper in PLOS Genetics now examines the role of DUF1220 , which encodes a protein domain of the NBPF genes. (epilepsygenetics.net)
  • These comparisons illustrate that the relative dosage of chromosomal segments is critical for normal development and phenotypic characteristics. (pnas.org)
  • Our results indicate that subtle changes in gene dosage across a chromosome can have significant phenotypic consequences. (mit.edu)
  • Nonetheless, changes in gene dosage (copy number variations) due to gene insertions or deletions can have significant phenotypic consequences. (wikipedia.org)
  • Indels can change the copy number of affected genes, which can create complex phenotypic trait variation through effects on gene expression. (usda.gov)
  • Disruption of the L2B gene (delta B strain) did not lead to any phenotypic alteration, whereas the inactivation of the L2A copy (delta A strain) produced a slow-growth phenotype associated with decreased accumulation of 60S subunits and ribosomes. (asm.org)
  • The existence of males and females in sexually reproducing organisms and the associated difference in phenotypic optima between sexes imposes an intergenomic conflict in both the evolution of gene sequences and of gene expression. (biomedcentral.com)
  • We employ here a geometric morphometric approach to identify subtle phenotypic differences caused by dosage effects of candidate genes. (elsevier.com)
  • Copy number variants (CNVs) reshape gene structure, modulate gene expression, and contribute to significant phenotypic variation. (omicsdi.org)
  • Transgenic and gene-knockout mice of individual genes are used to investigate the consequences of functional gene-dosage of the candidate genes. (weizmann.ac.il)
  • Finally, we have identified a number of candidate genes that may play important roles in the disease process or in myelination per se. (uzh.ch)
  • Validation of the circular CV for mouse transgenesisAs proof-of-principle for the use of the circular CV for the overexpression of XLID- (candidate-) genes in mice we modified BACs RP11-119A22 and RP11-51C14 encoding MECP2 and SOX3, respectively, and inserted them into the CV via Cre-loxP recombination. (kuleuven.be)
  • Copy numbers of a few of these genes have expanded during human evolution recently, turning these genes into potential candidate genes for human disease. (epilepsygenetics.net)
  • Several studies have quantified the gene dosage effect experimentally and shown that the levels of expression of genes vary up to fivefold depending on their chromosomal location ( 5 , 7 , 8 ). (asm.org)
  • Increased expression of genes involved in cell cycle regulation and DNA replication is characteristic and specific for the early stage in Pmp22-/- mice, supporting a primary function of PMP22 in the regulation of Schwann cell proliferation. (uzh.ch)
  • Both Tr and Pmp22tg mice show strongly reduced expression of genes important for cholesterol synthesis at P4, a characteristic that is common to all three mutants at P60. (uzh.ch)
  • RNA sequencing of sorted Neurog3(+/-) cells uncovered enriched expression of genes characteristic for both goblet and enteroendocrine cells, indicating the mixed lineages arose from Neurog3+ progenitors. (umassmed.edu)
  • article{e4545f11-fcca-422e-8307-a31e151cdeb0, abstract = {To ascertain the epigenomic features, i.e., the methylation, non-coding RNA, and gene expression patterns, associated with gain of i(12p) in Pallister-Killian syndrome (PKS), we investigated single cell clones, harboring either disomy 12 or tetrasomy 12p, from a patient with PKS. (lu.se)
  • abstract = "In 2009, we described the first generation of the chromosome 18 gene dosage maps. (elsevier.com)
  • By computing the mean expression ratio of all X-linked genes to all autosomal genes (X:A), we found that all samples displayed some levels of X chromosome upregulation. (g3journal.org)
  • Gene dosage is known to be related to the amount of gene product the cell is able to express, however, amount of gene product produced in a cell is more commonly dependent on regulation of gene expression. (wikipedia.org)
  • In human, this extra regulation is achieved through extensive microRNA targeting of genes coding for extremely vulnerable proteins. (rice.edu)
  • Additionally, we demonstrate that Hand2 and Phox2b are necessary for Hand1 transcriptional regulation, and that transcriptional regulation is sensitive to Hand2 gene dosage. (jneurosci.org)
  • data from Drosophila melanogaster [ 3 ] and mice [ 4 ] indicate that as much as 50% of all protein-coding genes might be subject to sex-specific regulation of mRNA expression. (biomedcentral.com)
  • Our long-term goal is to describe the molecular mechanisms used to target genes for coordinate regulation, the essential initial step in their regulation. (grantome.com)
  • Guided by strong preliminary data, we propose the following novel mechanism for identifying genes for coordinate regulation: CLAMP and the MSL complex associate inter-dependently, thereby generating a positive feedback amplification system that creates X- specificity from a two-fold X-enrichment of MRE sequences. (grantome.com)
  • The rationale for this work is that determining how the MSL complex specifically targets the X-chromosome will yield key insight into how genes are identified for coordinately regulation within sub-nuclear domains. (grantome.com)
  • Our proposed research is significant because we expect to describe for the first time the previously unknown mechanism that allows MSL complex to identify its high affinity sites, thereby defining the critical first step in establishing coordinate gene regulation. (grantome.com)
  • Defining the novel mechanism by which CLAMP and the MSL complex function together to generate a domain of enhanced transcription is likely to provide key insight into how genes are identified for coordinate regulation across species. (grantome.com)
  • Our proposed research is relevant to public health because loss of precise regulation of genes underlies a large number of diseases including autism 10 and Chron's disease 11. (grantome.com)
  • Our research addresses the critical initial step in the coordinate regulation of genes, identifying target genes for subsequent regulation. (grantome.com)
  • Here, we uncoupled X chromosome dose from sex-specific gene regulation in C. elegans to determine the effect of each on X expression. (desdaughter.com)
  • As a result, somatic sex-biased expression is almost entirely due to sex-specific gene regulation. (desdaughter.com)
  • In support of the presence of gene-by-gene DC, the extent of up-regulation in males was indeed higher for neo-X-linked genes with pseudogenized neo-Y-linked homologs than for neo-X-linked genes with functional neo-Y-linked homologs. (edu.sa)
  • Further molecular evolutionary analysis also supports the idea that many individual neo-X-linked genes first acquired the potential for up-regulation, which then enabled the pseudogenization of neo-Y-linked homologs, without serious deleterious effects on male fitness. (edu.sa)
  • Furthermore, endogenous Brn3a expression levels in the sensory ganglia of Brn3a(+/+) and Brn3a(+/-) mice are similar, demonstrating that autoregulation can compensate for the loss of one allele by increasing transcription of the remaining gene copy. (uniprot.org)
  • We also investigated the effect of the allele dosage in the prediction, i.e. , considering tetraploid (GS-TD) or diploid (GS-DD) allele dosage. (g3journal.org)
  • One way organisms might respond to such sexual antagonism is to evolve sex-biased gene expression, in which the fixation of a sexually antagonistic allele (beneficial in one sex whilst being costly to the other) is followed by the evolution of modifiers to down-regulate gene expression in one sex [ 1 ]. (biomedcentral.com)
  • The Polycomb (Pc) group of genes are required for maintenance of cell determination in Drosophila melanogaster. (nih.gov)
  • It has been shown experimentally in Drosophila melanogaster that the X is unusual when it comes to genes conferring sexual antagonism [ 15 ]. (biomedcentral.com)
  • Drosophila, like mammals 4, increase the transcript levels of a large number of diversely regulated genes along the length of the single male X-chromosome precisely two-fold relative to each female X-chromosome 5. (grantome.com)
  • The expression of constitutively expressed genes can vary up to fivefold based on chromosomal location, but it is not clear what level of variation would occur in naturally regulated operons. (asm.org)
  • Our findings demonstrate that, at least for the tufB operon, gene dosage is probably not the dominant force selecting for a chromosomal location close to OriC. (asm.org)
  • We conclude, at least for tufB , that forces other than gene dosage may be significant in selecting for chromosomal location. (asm.org)
  • Monoallelic ATR gene targeting in MLH1‐deficient HCT 116 colon carcinoma cells resulted in hypersensitivity to genotoxic stress accompanied by dramatic increases in fragile site instability, and chromosomal amplifications and rearrangements. (embopress.org)
  • As a result, interacting partners should be co-expressed to avoid dosage imbalance effects. (rice.edu)
  • These results suggest that extremely vulnerable proteins resorting to aggregation to buffer the deleterious consequences of dosage imbalance. (rice.edu)
  • Regarding the ACE polymorphism, animals harboring 3 copies of the ACE gene, which is accompanied by increased synthesis of Ang II, demonstrated left ventricular hypertrophy, higher pressure values, overt proteinuria, and risk of nephropathy, which is probably associated with autonomic imbalance ( 9 - 11 ). (scielo.br)
  • This solved the dosage imbalance of X-linked genes in males, yet subjected females to quadruple levels of X expression. (g3journal.org)
  • However, a mechanism linking S10 dosage to cell physiology has still not been determined. (ruc.dk)
  • The objective of this study was to determine the biological relevance associated with the translational mechanism responsible for expression of the nested p22 and p19 genes. (apsnet.org)
  • These results suggest that control of tombusvirus p22 and p19 protein ratios and dosage through context-dependent leaky scanning provides a co-translational mechanism to coordinate their biological activities. (apsnet.org)
  • Dissecting the mechanism by overexpressing the H-locus, we identified one gene has being the main driver, MRPA, responsible for Sb III sequestration. (uantwerpen.be)
  • Gene dosage is thus a very important mechanism for the acquisition of antimony resistance and MRPA amplification is the first one emerging in natural and experimental conditions. (uantwerpen.be)
  • 2017. Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes . (cardiff.ac.uk)
  • We propose a model of XY/ZW evolution incorporating such preexisting dosage sensitivities in determining the evolutionary fates of individual genes. (mit.edu)
  • Here we show in both humans and yeast that haploinsufficient genes generally do not duplicate more frequently than haplosufficient genes. (genetics.org)
  • Consequently, haploinsufficient genes should have higher duplicabilities than haplosufficient genes, which was reported to be true in humans ( K ondrashov and K oonin 2004 ). (genetics.org)
  • The broad long-term objective of our research is to elucidate, at the molecular level, how an extra copy of otherwise normal genes produces pathophysiological conditions in humans, particularly in patients with DS. (weizmann.ac.il)
  • These data were relevant to humans ACKD, as cystic genes expression and the rate of cell proliferation were also increased. (uzh.ch)
  • Conclusions: In addition to the essential functions of PERK in β-cells as revealed by severely diabetic phenotype in humans and mice completely deficient for PERK, reducing Perk gene expression by half showed that intermediate levels of PERK have a profound impact on β-cell functions and glucose homeostasis. (elsevier.com)
  • In humans of European background, only about 15-20% carry the Met form of the COMT gene in both copies of their 22 nd chromosome. (blogspot.com)
  • I had naively expected that comparing humans and great apes would naturally point towards a particular class of brain-expressed genes that made us human. (epilepsygenetics.net)
  • Interestingly, the three Pmp22 mutants exhibited distinct profiles of gene expression, suggesting different disease mechanisms. (uzh.ch)
  • They suggest that this high level of retention is due to constraints arising from gene dosage, rather than other proposed mechanisms. (biomedcentral.com)
  • Selection that depends on gene dosage can involve two different mechanisms. (biomedcentral.com)
  • The combination of targeting rare immunodeficiency genes with large case load of clinical NGS testing for rare immunological and related disorders allowed for the opportunity to discover novel CNVs and expand our understanding of disease mechanisms in this group of genetically heterogeneous disorders. (jtggjournal.com)
  • The evolutionary process leading to the fixation of newly duplicated genes is not well understood. (genetics.org)
  • However, the real differences were found in immune genes, highlighting our constant evolutionary struggle against parasites . (epilepsygenetics.net)
  • In this figure, all of the duplicated copies have been retained as functional genes, but that is not the most likely outcome with increasing evolutionary time. (beds.ac.uk)
  • Approximately a quarter of classic RTT cases, however, do not have an identifiable mutation of the MECP2 gene. (nih.gov)
  • Here we show that the accumulation of a single point mutation, G2576T, in the different copies of this gene causes stepwise increases in resistance, impairment of the biological fitness, and cross-resistance to quinupristin-dalfopristin and chloramphenicol. (asm.org)
  • S. aureus possesses five to six rRNA ( rrn ) operons ( 14 ), which suggests that the presence of a resistance-mediating mutation in one, several, or all of the 23S rRNA gene copies might be associated with gradually increased levels of resistance. (asm.org)
  • Moreover, small deletions or point mutation that cause gene conversion from SMN1 to SMN2 have been found in patients in whom SMN1 was present ( 8 ). (aaccjnls.org)
  • EGFR gene dosage was not associated with FISH positivity (P = 0.15), relative mRNA expression (P = 0.27), EGFR mutation status (P = 0.39), and EGFR protein expression (P = 0.35). (nih.gov)
  • Here, we investigated amygdala dysfunction and its relation to socioemotional deficits and FMR1 gene expression in children and adolescents on the FX spectrum (i.e., individuals whose trinucleotide CGG repeat expansion from 55 to over 200 places them somewhere within the fragile X diagnostic range from premutation to full mutation). (elsevier.com)
  • Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage. (cdc.gov)
  • The pathologic effects of MYBPC3 and MYH7 were found to be independent of gene mutation location. (cdc.gov)
  • Several systems biology approaches were applied to identify key molecular players underlying KS comorbidities: Identification of co-expressed modules as well as central hubs and gene dosage perturbed protein complexes in a KS comorbidity network build from known disease proteins and their protein-protein interactions. (dtu.dk)
  • They assumed that if halving the amount of gene product is deleterious to an organism ( i.e. , haploinsufficiency), doubling the amount would be beneficial. (genetics.org)
  • 3. Despite a halved functional gene dosage, heterozygous muscles display an average G(Cl), which is not significantly different from that of homozygous wild-type animals. (uni-bielefeld.de)
  • In addition, modulation of Perk dosage specifically in β-cells showed that the glucose homeostasis phenotype of Perk heterozygous mice is determined by reduced expression of PERK in the β-cells. (elsevier.com)
  • We use mouse strains with specific gene modifications (knockouts and knockins) to compare heterozygous animals with controls from the same stock, which is expected to be equivalent to a change of gene expression of the respective locus. (elsevier.com)
  • Gene dosage alteration of L2 ribosomal protein genes in Saccharomyces cerevisiae: effects on ribosome synthesis. (asm.org)
  • Nomura, M. / Expression of ribosomal protein genes cloned in a hybrid plasmid in Escherichia coli : Gene dosage effects on synthesis of ribosomal proteins and ribosomal protein messenger ribonucleic acid . (umn.edu)
  • On the basis of these and other results, we conclude that selection for higher gene dosage does not play a major role in driving the fixation of duplication genes. (genetics.org)
  • In cases like this, gene duplication may enhance the organismal fitness immediately, driving the adaptive fixation of duplicate genes. (genetics.org)
  • Here we discuss these results in relation to the various models proposed for gene duplication and retention. (biomedcentral.com)
  • If the initial duplication event is evolutionarily neutral, the duplicated genes will become fixed in the population with a probability dependent on the inverse of the effective population size. (biomedcentral.com)
  • It has been suggested, however, that the initial duplication event is likely to be deleterious for gene duplicates with functional regulatory regions, because of the metabolic cost of producing extra protein [ 2 ]. (biomedcentral.com)
  • While relaxation of selective constraint is generally thought to occur after gene duplication, negative selection, which discards changes, apparently returns quickly. (biomedcentral.com)
  • This gene family is located within a segmental duplication region in the 1q21.1 region. (epilepsygenetics.net)
  • The paralogous genes RABL2A (chr2) and RABL2B (chr22) emerged by duplication of a single gene in the human-chimpanzee ancestor and share a high degree of sequence similarity. (mpg.de)
  • In free-living bacteria, highly expressed genes involved in transcription and translation are generally located close to the origin of replication ( 1 , 2 ). (asm.org)
  • 9:273-277, 1985), the difference in expression of the two gene copies could be accounted for via differential transcription activity. (asm.org)
  • EGFR mRNA expression was measured by real-time quantitative reverse transcription-PCR in 64 patients, and EGFR gene dosage was analyzed by real-time quantitative PCR in 82 patients from paraffin-embedded specimens. (nih.gov)
  • This was highly correlated with transcription levels, supporting the adaptive function of gene dosage. (uantwerpen.be)
  • Most genes present in CNVs show no evidence of increased or diminished transcription, and the fraction of such dosage-insensitive CNVs is greater in heterozygotes. (omicsdi.org)
  • More than 70% of the dosage-sensitive CNVs are recessive with undetectable effects on transcription in heterozygotes. (omicsdi.org)
  • 2019. Imprinted genes influencing the quality of maternal care . (cardiff.ac.uk)
  • Both under- and overexpression of genes could lead to deleterious biological consequences. (rice.edu)
  • Genes encoding vulnerable proteins need to be highly co-expressed with their interacting partners. (rice.edu)
  • Highly dosage sensitive genes encode proteins which are vulnerable to water attack. (rice.edu)
  • The 85 genes encoding extremely vulnerable proteins contain the five confirmed yeast prions. (rice.edu)
  • Changes of that order of magnitude in expression of important proteins, such as ribosomal proteins or elongation factors, would lead to a significant reduction in bacterial growth rate ( 9 , 10 ), potentially explaining the strong selection for gene location on the chromosome. (asm.org)
  • Tomato bushy stunt virus (TBSV) encodes a small gene (p19) nested within the cell-to-cell movement gene (p22), and their translation yields two proteins with separate activities for virus spread and symptom induction. (apsnet.org)
  • Changes in the dosage or ratios of p22 and p19 proteins failed to noticeably affect virus replication or movement in Nicotiana spp. (apsnet.org)
  • Thus a screen for elevated gene dosage can routinely be performed for identification of P. pastoris clones with high expression levels of aquaporins and other classes of membrane proteins. (biomedcentral.com)
  • We reconstructed gene-by-gene dosage sensitivities on the ancestral autosomes through phylogenetic analysis of microRNA (miRNA) target sites and compared these preexisting characteristics to the current status of Y-linked and X-linked genes in mammals. (mit.edu)
  • These dosage-sensitive genes may confer an advantage upon copy number change, but more typically they are associated with disease, including heart disease, cancers and neuropsychiatric disorders. (biomedcentral.com)
  • Gene balance effects are hypothesized to result from stoichiometric differences among members of macromolecular complexes, the interactome, and signaling pathways. (pnas.org)
  • These slight gene dosage differences are responsible for variation in gene expression depending on the position on the chromosome. (wikipedia.org)
  • We find that subtle but significant shape differences are caused by differences in gene dosage of several of these genes. (elsevier.com)
  • These systems have deep differences, but in both cases we see that even a transient change in relative gene dosage has noticeable consequences. (biomedcentral.com)
  • Analysis of relative gene dosage and expression differences of the paralogs RABL2A and RABL2B by Pyrosequencing. (mpg.de)
  • further emphasizing the need for methods to identify functionally relevant genes for tumor biology and progression within SCNAs. (genetics.org)
  • We applied the Agilent 2100 Bioanalyzer, a microflu- idics-based electrophoresis instrument, and introduced an accurate and consistent parameter, the relative pro- duct yield ratio (ROY), to detect somatic gene dele- tions in tumor cells. (journaldatabase.info)
  • Susumu Ohno hypothesized that upregulation of the X-linked genes in the heterogametic sex (XY) would be necessary to maintain their expression to the levels of the diploid autosomes ( Ohno 1966 ). (g3journal.org)
  • In this system gene expression of sex-specific loci is reduced in the heterogametic sex i.e. the females in ZZ/ZW systems and males in XX/XY systems. (wikipedia.org)
  • Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. (nih.gov)
  • We have generated mice lacking a functional p300 gene. (nih.gov)
  • Here, we define a 1007 bp cis -regulatory element 5′ of the Hand1 gene sufficient to drive reporter expression within the sympathetic chain of transgenic mice. (jneurosci.org)
  • The present study aimed to investigate cardiovascular autonomic modulation and angiotensin II (Ang II) activity in diabetic mice that were genetically engineered to harbor two or three copies of the angiotensin-converting enzyme gene. (scielo.br)
  • Diabetic and non-diabetic mice harboring 2 or 3 copies of the angiotensin-converting enzyme gene were used in the present study. (scielo.br)
  • This was most pronounced at the top and bottom of the gene dosage hierarchy, with a 1.5-fold overrepresentation of Brg1 +/+ ;Brm +/+ mice and a corresponding 1.6-fold underrepresentation of Brg1 +/− ;Brm −/− mice. (deepdyve.com)
  • Comparing the effect sizes of gene dosage changes to the variation found in natural populations of mice as well as quantitative trait loci (QTL) effects on mandible shape, we find that the effect sizes caused by gene dosage changes are at the lower end of the spectrum of natural variation, but larger than the average additive effects found in QTL studies. (elsevier.com)
  • Gene dosage reductions of Trf1 and/or Tin2 induce telomere DNA damage and lymphoma formation in aging mice. (telomerescience.com)
  • The genes that are closer to the origin site would be replicated first and would consequently be present in two copies in the cell for a longer time than the genes that are closer to the termination site. (wikipedia.org)
  • Animals were divided into 4 groups: diabetic groups with two and three copies of the angiotensin-converting enzyme gene (2CD and 3CD) and the respective age-matched non-diabetic groups (2C and 3C). (scielo.br)
  • Because bacteria have overlapping cycles of replication, genes located close to the origin will often be present in multiple copies, and this is thought to be of selective benefit where high levels of expression support high growth rate. (asm.org)
  • The wild-type phenotype was restored in the delta A strains by transformation with extra copies of the intact L2A or L2B gene. (asm.org)
  • To characterize the domain V regions of each of the five 23S rRNA gene copies from strain T991 and its descendants, these genes were individually amplified as previously described ( 15 ). (asm.org)
  • The five T991 derivatives selected under linezolid selective pressure, however, showed a G2576T substitution in domain V within one or more of their 23S rRNA gene copies (Table 1 ). (asm.org)
  • i.e., the higher the resistance the more gene copies showed the G2576T exchange (Table 1 ). (asm.org)
  • Whereas the dose dependent association between the number of active copies of the SHOX gene and height is well established, studies addressing a more subtle variability between the quality of fetal growth, the severity of post natal height deficit and karyotype subgroups in Turner syndrome (TS) are still limited. (eurospe.org)
  • However, there are also genes that are highly copy number variable, sometimes present at 80 copies or more. (epilepsygenetics.net)
  • The ability to visualise and quantify face shape effects of gene dosage is of major benefit for determining whether a CNV is the cause of the phenotype of an individual and for predicting reciprocal consequences. (ox.ac.uk)
  • Main research interests are mammalian epigenetics with a focus on imprinted genes, embryonic growth and the early programming of adult diseases. (cardiff.ac.uk)
  • However, little is known about the action of single genes on adult mandible shape so far, since most developmentally relevant genes are already required during embryogenesis, i.e., knockouts lead to embryonic death or severe deformations, before the mandible is fully formed. (elsevier.com)
  • Conversely, transgenic overexpression of Brn3a in the trigeminal ganglion suppresses the expression of the endogenous gene. (uniprot.org)
  • In so doing, we have proved the gene-dosage effect theory in trisomy 21 and opened the door into a new era in DS research. (weizmann.ac.il)
  • Here we systematically explored the effect of induced gene dosage variation on quantitative trait variation in Populus . (usda.gov)
  • The distance from OriC had only a small effect on growth rate, consistent with this operon having the natural ability to upregulate expression and compensate for reduced gene dosage. (asm.org)
  • In contrast, when the total EF-Tu concentration was limiting for the growth rate ( tufA deleted), we observed a strong gene dosage effect when tufB was located further from OriC. (asm.org)
  • However, it remains unclear whether SCA6 shows a gene dosage effect, defined by earlier age-of-onset in homozygotes than heterozygotes. (researchmap.jp)
  • These data suggest a mild clinical and neuropathological gene dosage effect in SCA6 subjects. (researchmap.jp)
  • This suggests that -while not directly causative- DUF1220 dosage may have a modifying effect on ASD severity. (epilepsygenetics.net)
  • The rs2108622 SNP of the CYP4F2 gene and its effect on warfarin dosing in these patients was accessed. (ac.ir)
  • The bacterial chromosome is present only in one copy per cell, but there can still be variation in gene dosage due to DNA replication which starts at the origin of replication and ends at the termination site. (wikipedia.org)
  • This location skew is thought to reflect selective advantages associated with gene dosage effects during the replication cycle. (asm.org)
  • This locational bias is thought to reflect a selection for maximum growth rate that can be achieved by increasing relative gene copy number and, therefore, expression, due to gene dosage effects associated with bacteria having overlapping cycles of chromosome replication under fast growth conditions ( 3 - 6 ). (asm.org)
  • We propose normative inversion of face shape, opposing difference from a matched norm, as a basis for investigating the effects of gene dosage on craniofacial development. (ox.ac.uk)
  • Thus, human females have the same number of expressed X-linked genes as do human males (XY), both sexes having essentially one X chromosome per cell, from which to transcribe and express genes. (wikipedia.org)
  • Since this regional-based approach proved effective for protein coding genes, it is natural to assess its application to noncoding exome sequence. (prolekare.cz)
  • recognizing that these three regions are only a subset of the relevant regulatory sequence for protein-coding genes. (prolekare.cz)
  • Cysts can be acquired, or they may appear during development or in postnatal life due to specific gene defects and lead to renal failure. (uzh.ch)
  • We define a 1007 bp evolutionarily conserved region (ECR) 5′ to the Hand1 locus sufficient to drive reporter gene expression throughout the developing and postnatal sympathetic ganglia (SG). (jneurosci.org)
  • Selection for increased gene dosage involves a positive selection pressure to increase expression from a locus that is already highly expressed and has little mutational capacity to increase its expression or concentration-dependent activity. (biomedcentral.com)
  • Thus, the Agilent 2100 Bioanalyzer is simple, accurate, quick, and ultimately able to replace conventional gel electrophoresis for the detection of somatic gene deletions. (journaldatabase.info)
  • From a biochemical reductionist perspective, biological function may be explained within a structural mechanistic context as the action of a gene, surface, motif or residue that result in a chemical reaction, activation or inhibition of an enzyme or receptor, or even a physiological process such as blood clotting or platelet aggregation. (frontiersin.org)
  • For example, gene dosage variation has been associated with various human chronic diseases. (usda.gov)
  • The first approach is based on comparing observed and predicted levels of standing human variation in the noncoding exome sequence of a gene. (prolekare.cz)
  • To assess whether noncoding sequence can predict genes that cause human disease through gene dosage aberration, we derive two measures: a phylogenetic conservation based score and a score reflecting intolerance to standing variation in a human population. (prolekare.cz)
  • By comparing clones carrying a single gene copy, we show a remarkable variation in recombinant protein expression between isoforms and that the poor expression observed for one of the isoforms could only in part be explained by reduced transcript levels. (biomedcentral.com)
  • We conclude that studying gene dosage effects have the potential to provide new insights into aspects of craniofacial development, variation, and evolution. (elsevier.com)
  • In yeast, the SIR2 gene determines the lifespan of mother cells, and adding an extra copy of SIR2 extends lifespan. (nih.gov)
  • We were able to determine all genotypes with different SMN1/SMN2 gene copy number ratios, which unambiguously diagnosed carrier status and the severity of SMA with 100% specificity. (aaccjnls.org)
  • Furthermore, we show that heterologous expression levels of all four aquaporin isoforms strongly respond to an increase in recombinant gene dosage, independent of the amount of protein expressed from a single gene copy. (biomedcentral.com)
  • By using this method we show that: (1) heterologous expression of all aquaporins investigated respond strongly to an increase in recombinant gene dosage (2) expression from a single recombinant gene copy varies in an isoform dependent manner (3) the poor expression observed for AtSIP1;1 is mainly caused by posttranscriptional limitations. (biomedcentral.com)
  • Once fixation occurs, if there is purely neutral evolution at the protein level, one copy of a duplicated gene will quickly become a pseudogene, leaving a single ancestral copy with an ancestral function. (biomedcentral.com)
  • Most studies determine sex biased gene expression without distinguishing between contributions from X chromosome copy number (dose) and the animal's sex. (desdaughter.com)
  • In addition, other genes that are highly copy number variable were boosted during recent human evolution . (epilepsygenetics.net)
  • We propose that gene expression level may provide a common basis for the pathogenic effects of many copy number variants. (biomedcentral.com)
  • A dramatic but transient form of dosage alteration occurs during every cell cycle where there is a drastic disruption to the relative ratios of gene copy number, with early-replicating DNA regions being twice as abundant as late-replicating regions during S-phase. (biomedcentral.com)
  • Dosage-sensitive CNVs that are up-regulated and down-regulated coincide with copy number increases and decreases. (omicsdi.org)
  • Earlier studies in developing mouse pancreas showed Neurog3 gene dosage in endocrine and exocrine cell fate allocation. (umassmed.edu)
  • At the initial stage of sex chromosome evolution, however, gene-by-gene (or localized) DC may also be necessary because the degeneration of Y-linked genes occurs independently at different times. (edu.sa)