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  • disease-causi
  • To overcome these technical challenges, we designed a custom high-resolution targeted exon-centric microarray (ECM) that has 1508 disease-causing genes including complementary genes to our laboratory's immunodeficiency focused next-generation sequencing (NGS) panels. (jtggjournal.com)
  • defects
  • As well as the well-documented epithelial defects, aberrant Pax6 dosage had profound effects on the corneal stroma and endothelium in both genotypes, including cellular vacuolation, similar to that reported for human macular corneal dystrophy. (uclan.ac.uk)
  • Some of the disorders included in these CGS are well-known disease entities due to single gene defects (e.g. (mhmedical.com)
  • mutations
  • 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)
  • 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)
  • 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)
  • A new gene copy must acquire the rare mutations that provide a new selectable function. (pnas.org)
  • These rare mutations can be acquired only if the gene copy remains in the population for a sufficient time and at a sufficient allele frequency. (pnas.org)
  • mice
  • 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)
  • 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)
  • 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)
  • To test this, we tripled the dosage of one of these genes, the ubiquitin protein ligase Ube3a , which is expressed solely from the maternal allele in mature neurons, and reconstituted the three core autism traits in mice: defective social interaction, impaired communication, and increased repetitive stereotypic behavior. (sciencemag.org)
  • Tripling the dosage of an autism- and Angelman syndrome-related gene in mice results in reduced glutamatergic synaptic transmission and autism behavioral traits. (sciencemag.org)
  • (kuleuven.be)
  • 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)
  • 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)
  • 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)
  • mutation
  • This classical model for the origin of genes with new functions has been called the mutation during nonfunctionality (MDN) model ( 7 ) or the neo-functionalization model ( 8 ). (pnas.org)
  • To assure retention of the extra copy, some form of selection must overcome opposing drift, mutation, recombinational segregation, and gene conversion. (pnas.org)
  • single gene
  • 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)
  • 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)
  • chromosomal
  • 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)
  • Despite
  • However, despite equal gene dosage a preferential expression of RABL2B in human tissues and lymphoblastoid cell lines was detected which is most pronounced in brain and placenta. (mpg.de)
  • phenotypes
  • Deletion of Tbx1 or Prodh (22q11 genes independently associated with 22q11DS phenotypes) does not similarly disrupt basal progenitors. (pnas.org)
  • 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)
  • sensitivity
  • Opposite effects on facial morphology due to gene dosage sensitivity. (ox.ac.uk)
  • 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)
  • functional
  • It enables face shape to be used as a relatively simple and inexpensive functional analysis of the gene(s) involved. (ox.ac.uk)
  • For most autosomal loci, deletion causes a reduction of gene dosage to structural and functional monosomy. (mhmedical.com)
  • disorders
  • 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)
  • Gene therapy is emerging as a therapeutic modality for treating disorders of the retina. (sciencemag.org)
  • Interestingly, this gene resides right next to the 1q21.1 region that is implicated in various neurodevelopmental disorders. (epilepsygenetics.net)
  • DUF1220 dosage is distributed in patients with autism spectrum disorders (ASD) in an almost Gaussian fashion, which is not much different from what is expected in the general population. (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)
  • postnatal
  • 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)
  • demonstrate
  • Mutational analyses revealed that the conserved Phox2 and E-box binding sites are necessary for proper cis -regulatory element activity, and expression analyses on both Hand2 conditionally null and hypomorphic backgrounds demonstrate that Hand2 is required for reporter activation in a gene dosage-dependent manner. (jneurosci.org)
  • Finally, we demonstrate that Hand1 is dispensable for normal tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DBH) expression in sympathetic neurons, even when Hand2 gene dosage is concurrently reduced by half. (jneurosci.org)
  • 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)
  • Thus
  • 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)
  • 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)
  • show
  • 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)
  • Some human genes show exclusive expression from a single parental homologue and no expression from the other homologue (i.e., genomic imprinting). (mhmedical.com)
  • human
  • These preclinical results provide guidance for optimal vector and dose selection in future human gene therapy trials to treat retinal diseases caused by loss of photoreceptors. (sciencemag.org)
  • 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)
  • In addition, other genes that are highly copy number variable were boosted during recent human evolution . (epilepsygenetics.net)
  • cortical
  • However, expression analysis implicates additional 22q11 genes that are selectively expressed in cortical precursors. (pnas.org)
  • We found that diminished 22q11 gene dosage in a 22q11DS mouse model compromises specific cortical neural stem cells, basal progenitors, and alters frequency and distribution of cortical projection neurons and GABAergic interneurons. (pnas.org)
  • effects
  • 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)
  • Amplification
  • When an altered ecological niche makes the minor innovation valuable, selection favors increases in its level (the amplification), which is most frequently conferred by increased dosage of the parent gene. (pnas.org)
  • locus
  • 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)
  • copy
  • A model is described by which selection continuously favors both maintenance of the duplicate copy and divergence of that copy from the parent gene. (pnas.org)
  • However, there are also genes that are highly copy number variable, sometimes present at 80 copies or more. (epilepsygenetics.net)
  • complexity
  • Gene-environment interaction has been invoked as a premise to explain the etiological complexity of HPE but identification of interacting factors has been extremely limited. (biologists.org)
  • candidate
  • 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)
  • function
  • Diminished hypothalamic bdnf expression and impaired VMH function are associated with reduced SF-1 gene dosage. (semanticscholar.org)
  • Maintaining a duplicated gene by selection for the original function would restrict the freedom to diverge. (pnas.org)