Functional variants human gene dosage. Medical search. Frequent questions

The sequencing of the human genome represents the ultimate triumph of this principle - the dis-assembly of an enormously complex living thing into its three billion molecular constituents. (dnalc.org)

More recently, the Mayo Clinic's pharmacogenomics program has employed these cell-based functional genomic techniques to identify the mechanisms responsible for individual variations in response to drugs for breast cancer and depression. (medpagetoday.com)
These data provide a foundational map of large SV in the morbid human genome and demonstrate a previously underappreciated abundance and diversity of cxSV that should be considered in genomic studies of human disease. (biomedcentral.com)
With regard to the "Biology" of genomes, several talks provided early results of elegant, yet massive, screens to better understand the biological and functional consequence of variation seen in either genomic disorders or cancer. (biomedcentral.com)
Gene and genome duplications are the primary source of new genes and have played a pivotal role in the evolution of genomic and organismal complexity [ 1 - 4 ]. (biomedcentral.com)
It is best to be aware of these definitions while sticking with the recommendations of the Human Genome Variation Society and to use ' sequence variant ' , ' alteration ' or ' allelic variant ' for any genomic change regardless of their frequency or phenotypic effects. (tripod.com)

Pharmacogenomics provides an opportunity to identify candidate genes for studying disease progression and outcomes. (cambridge.org)
We have developed a novel algorithm (PVP) which augments existing strategies by using the similarity of the patients phenotype to known phenotype-genotype data in human and model organism databases to further rank potential candidate genes. (plos.org)
The simplest forms of filters are minor allele frequency (MAF), candidate genes or variants, or considering the exome. (biomedcentral.com)

RNA-sequencing (RNA-seq) is a powerful technique for the identification of genetic variants that affect gene-expression levels, either through expression quantitative trait locus (eQTL) mapping or through allele-specific expression (ASE) analysis. (biomedcentral.com)
eQTL mapping on individual tissues revealed that a limited number of samples already suffice to identify tissue-specific eQTLs for known disease-associated genetic variants. (biomedcentral.com)
Given the exponential growth of the number of publicly available RNA-seq samples, we expect this approach will become especially relevant for studying the effects of tissue-specific and rare pathogenic genetic variants to aid clinical interpretation of exome and genome sequencing. (biomedcentral.com)
conducted a comprehensive mutational analysis of the ARSA gene in MLD patients, revealing specific genetic variants associated with disease severity. (creativebiomart.net)
This raises the need to filter, or prioritize, or jointly test genetic variants. (biomedcentral.com)
Recently, multiple annotation tools have become available using several databases and algorithms that predict functional effects of genetic variants. (biomedcentral.com)
This article discusses approaches that filtered or prioritized genetic variants, regions, or genes. (biomedcentral.com)
Many researchers filter genetic variants. (biomedcentral.com)

These insertions, deletions, inversions, and duplications result in changes in the physical arrangement of genes on chromosomes. (nature.com)
The human X and Y chromosomes are useful tools for inferring human demography, and crucial for our understanding of human health. (grantome.com)
My research has focused on the integration of these chromosomes to build comprehensive analyses of human history and utilizing an evolutionary approach to characterize sex-bias in gene expression. (grantome.com)
First, we will focus on development and extensive testing of novel methodology for accurately accounting for technical variation that affects alignment and variant calling on the sex chromosomes. (grantome.com)
Current alignment pipelines do not account for the shared homology between the X and Y chromosome, resulting in mis-mapping of reads between the sex chromosomes and reduced power for variant calling. (grantome.com)
Our methodology will incorporate sex chromosome biology to improve variant calling on the sex chromosomes. (grantome.com)
In the second keynote address, David Page (Whitehead Institute) investigated overlapping sets of genes retained on sex chromosomes over the course of evolution from autosomes (see Fig. 1 ). (biomedcentral.com)
Interestingly, human X chromosome and its bird counterpart Z chromosome retain a much higher number of autosomal genes than the Y and W chromosomes in humans and birds, respectively. (biomedcentral.com)

Proteins supported by a single continuous cDNA sequence lead to underlining the name/ending of the variant. (nih.gov)
The identification of an inactivating missense mutation in NANOS3 suggests a mechanism for POI involving increased primordial germ cells (PGCs) apoptosis during embryonic cell migration and highlights the importance of NANOS proteins in human ovarian biology. (hindawi.com)
The Mayo team used their established deep mutational scanning (DMS) platform to determine the functional implications of 433 human genome variants for ACE2 and TMPRSS2 by analyzing the amount of the encoded proteins. (medpagetoday.com)
Notch receptors are single-pass transmembrane proteins composed of functional Notch extracellular domain (NECD), transmembrane (TM), and Notch intracellular domains (NICD). (frontiersin.org)
To determine how the ASAP complex interacts with the EJC core, we performed in vitro coprecipitation assays 3 with Tandem Affinity Purification (TAP)-tagged recombinant proteins corresponding to full-length human SAP18, RNPS1 and ACINUS. (nature.com)
A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. (biomedcentral.com)

Haploinsufficiency may arise from a de novo or inherited loss-of-function mutation in the variant allele, such that it yields little or no gene product (often a protein). (wikipedia.org)
While the long-term goal of the SSPsyGene Consortium is to build a comprehensively annotated resource describing the CNS function of all neurodevelopmental and psychiatric disorder risk genes, the current target for the initiative is 100-250 protein coding genes. (nih.gov)
The goal of this initiative is to fill a very specific knowledge gap area, which is that many protein-coding genes are now associated with NPD risk, but their basic neurobiology remains poorly understood. (nih.gov)
The RNA-binding protein NANOS3 poses as an interesting candidate gene for POI since members of the Nanos family have an evolutionarily conserved function in germ cell development and maintenance by repressing apoptosis. (hindawi.com)
Functional studies revealed that some variants increased protein expression, which might increase viral susceptibility and severity, while other variants decreased protein expression, possibly exerting a protective effect. (medpagetoday.com)
Additionally, we observed strong ASE effects for 34 rare pathogenic variants, corroborating previously observed effects on the corresponding protein levels. (biomedcentral.com)
Similar to the focus on structural variation as opposed to SNV's in protein coding genes, there were a number of excellent talks defining variation in non-coding regions from genome sequencing datasets of different patient populations. (biomedcentral.com)
To facilitate analysis of this type of non-coding variation dataset, the group is now developing a non-coding constraint metric (parallel to the constraint metrics for protein coding genes). (biomedcentral.com)
A denatured recombinant protein with a N-Terminal His-tag and corresponding to the amino acids 21-509 of Human Arylsulfatase A/ARSA. (creativebiomart.net)
The human arylsulfatase A (ARSA) protein is a critical enzyme involved in the metabolism of sulfated compounds. (creativebiomart.net)
In the developing male (XY) gonad, sex-determining region of the Y (SRY) protein acts to up-regulate expression of the related gene, SOX9 , a transcriptional regulator that in turn initiates a downstream pathway of testis development, whilst also suppressing ovary development. (plos.org)
The byg mutation is an A to T transversion causing a premature stop codon in the gene encoding MAP3K4 (also known as MEKK4), a mitogen-activated protein kinase kinase kinase. (plos.org)
The Y-linked sex determining gene SRY regulates this process by initiating a pathway of gene and protein expression, including the expression of critical autosomal genes such as SOX9 . (plos.org)
This mutant, which we called boygirl ( byg ), was shown to contain an early stop codon that disrupts the autosomal gene encoding MAP3K4, a component of the mitogen-activated protein kinase (MAPK) signaling pathway. (plos.org)
We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. (biomedcentral.com)
However, ~20,000 is the number of protein-coding genes. (tripod.com)
This gene provides instructions for making a protein called progranulin. (medlineplus.gov)
GRN gene mutations that cause CLN11 disease result in a complete loss of functional progranulin protein. (medlineplus.gov)
Having a mutation in both copies of the GRN gene eliminates production of any functional progranulin protein. (medlineplus.gov)
The parents of individuals with CLN11 disease each carry one copy of the mutated GRN gene in every cell and generally produce about half the normal amount of progranulin protein. (medlineplus.gov)
Some people with two GRN gene mutations that allow the production of some functional progranulin protein develop GRN -related frontotemporal lobar degeneration. (medlineplus.gov)

Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type phenotype. (wikipedia.org)
clarification needed] In the alternative case of haplosufficiency, the loss-of-function allele behaves as above, but the single standard allele in the heterozygous genotype produces sufficient gene product to produce the same, standard phenotype as seen in the homozygote. (wikipedia.org)
Haplosufficiency accounts for the typical dominance of the "standard" allele over variant alleles, where the phenotypic identity of genotypes heterozygous and homozygous for the allele defines it as dominant, versus a variant phenotype produced only by the genotype homozygous for the alternative allele, which defines it as recessive. (wikipedia.org)
When the mutant gene is inherited with a high-expressivity allele, there is no disease phenotype. (wikipedia.org)
show that rs1344706 or variation in linkage disequilibrium is functional in human brain, and validate the intermediate phenotype strategy in psychiatry. (dnalc.org)
This gene is associated to a phenotype (DumPY : shorter than wild-type). (nih.gov)
Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. (plos.org)
Carrier screening is a term used to describe genetic testing that is performed on an individual who does not have any overt phenotype for a genetic disorder but may have one variant allele within a gene(s) associated with a diagnosis. (acog.org)
The other one is that mutation is any variation in the gene that causes an obvious change in phenotype whereas polymorphisms do not cause any obvious phenotypic variation. (tripod.com)
three different genes may cause the same phenotype). (tripod.com)

While it is anticipated that assays should aim to characterize 100-250 genes, some phenotypes and assay formats may be more amenable to moderate scale screening against a subset (50-100) of the gene set. (nih.gov)
Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. (plos.org)
We address the problem of how to distinguish which of the many thousands of DNA sequence variants carried by an individual with a rare disease is responsible for the disease phenotypes. (plos.org)
Consequently, several anterior segment dysgenesis phenotypes are associated with mutations in genes expressed during neural crest development. (molvis.org)
FOXD3 variants increase the risk of anterior segment dysgenesis phenotypes in humans. (molvis.org)
Almeida MR, Macario MC, Ramos L, Baldeiras I, Ribeiro MH, Santana I. Portuguese family with the co-occurrence of frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis phenotypes due to progranulin gene mutation. (medlineplus.gov)

If smORFs present within lncRNAs can encode functional small peptides, they can also constitute cis -regulatory elements involved in lncRNA decay. (mdpi.com)
Rare SVs are more likely to disrupt coding and regulatory non-coding loci, particularly when truncating constrained and disease-associated genes. (biomedcentral.com)
Patrick Short from Matthew Hurles' group at the Wellcome Sanger Institute investigated the de novo mutation rate in regulatory elements using over 10,000 whole genome sequencing samples from the Deciphering Developmental Disorders (DDD) study and found that de novo mutations (DNMs) in these individuals are enriched within the ultra-conserved elements and these variants may contribute to 1-3% of subjects without a diagnostic finding. (biomedcentral.com)
Taking a different approach based on gene expression, Pejman Mohammadi (of the Scripps Research Institute, formerly at the New York Genome Center) presented work utilizing allele-specific gene expression data to identify genetic regulatory outliers in a cohort of patients with muscular dystrophy using Analysis of Expression Variance- Dosage Outlier Test (ANEVA-DOT). (biomedcentral.com)
Wendy Bickmore (University of Edinburgh) described the role of regulatory variation in developmental genes in Mendelian diseases. (biomedcentral.com)
Many of the above-listed tools also provide information on regulatory elements that control gene activity. (biomedcentral.com)
Gene regulatory network (GRN) inference that incorporates single-cell RNA-seq (scRNA-seq) differentiation trajectories or RNA velocity can reveal causal links between transcription factors and their target genes. (bilkent.edu.tr)
We also applied Velorama to study cell differentiation in pancreas, dentate gyrus, and bone marrow from real datasets and obtained intriguing evidence for the relationship between regulator interaction speeds and mechanisms of gene regulatory control during differentiation. (bilkent.edu.tr)
We are currently pursuing studies of the dominant signaling and gene regulatory networks that control this process, including the Ras/MAPK cascade, which is required for stem cell-mediated self-renewal and the p53 transcription factor family member, p63, which is required for epidermal differentiation. (stanford.edu)
In addition to classical gene regulatory networks noted above, we have recently identified a central role for additional biologic mechanisms, namely gene regulation by chromatin regulators and by noncoding RNAs. (stanford.edu)
Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm. (ucsf.edu)
The life of a gene product, from transcription to degradation, is controlled by a series of regulatory decisions. (biomedcentral.com)
Distal and proximal cis-regulatory elements sense X chromosome dosage and developmental state at the Xist locus. (axonmedchem.com)
The sensitivity and specificity of such testing can now be improved as a result of the recent discovery of the Cystic Fibrosis Transmembrane Conductance Regulatory (CFTR) gene. (cdc.gov)
The discovery of the Cystic Fibrosis Transmembrane Conductance Regulatory (CFTR) gene (5) renewed interest in this possibility, as the sensitivity and specificity of testing could be improved through DNA-based testing. (cdc.gov)

Despite these discoveries, the patterns, rates, and properties of cxSVs have primarily been the focus of cancer genomics and such rearrangements remain largely underappreciated in the human germline. (biomedcentral.com)

American Journal of Human Genetics. (wikipedia.org)
We show, by using an imaging genetics approach, that healthy carriers of rs1344706 risk genotypes exhibit no changes in regional activity but pronounced gene dosage-dependent alterations in functional coupling (correlated activity) of dorsolateral prefrontal cortex (DLPFC) across hemispheres and with hippocampus, mirroring findings in patients, and abnormal coupling of amygdala. (dnalc.org)
Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. (plos.org)
Our experimental focus is on the mammalian setting using multiomics, informatics, mouse genetics, human genetics, single cell studies, and new human tissue platforms. (stanford.edu)
These new models, which we term Multi-Functional Human Tissue Genetics, allow up to 10 alleles or more to be altered simultaneously, permitting genetic experiments with an unprecedented degree of rapidity and complexity. (stanford.edu)
To address this and to also study the oncogenic potential of unregulated function of dominant regulators of epithelial homeostasis noted above, we developed Multi-Functional Human Tissue Genetics noted above which, when combined with skin tissue regeneration on immune deficient mice, has permitted the molecular reconstruction of events sufficient to trigger human cancer. (stanford.edu)
As a result of the rapid advances in genetics technology and the Human Genome Project, most of the estimated 100,000 genes in humans will be identified by the year 2005 (1). (cdc.gov)

To maximize the potential disease relevance, genes with a genome-wide significant excess burden of loss-of-function mutations in NPDs such as intellectual disability/developmental delay, autism spectrum disorder, and schizophrenia are the focus. (nih.gov)
DAX1 and SF1 messenger ribonucleic acid (mRNA) are expressed in the developing urogenital ridge, gonads, adrenal gland, pituitary gland, and hypothalamus, suggesting a dose-dependent role for both of these genes interacting as transcription factors important in a cascade of developmental gene expression. (medscape.com)

Can I include analysis of copy number variants (CNVs) associated with disease risk? (nih.gov)
Copy number variations (CNVs) have been linked to dozens of human diseases, but can they also represent the genetic variation that was so essential to our evolution? (nature.com)
Recently, a collaboration of international research laboratories has begun compiling a complete catalog of existing CNVs in the human genome. (nature.com)
Taken together, these CNVs cover approximately 360 megabases, or 12% of the human genome. (nature.com)
2005) revealed that the majority of CNVs were shared between the human and chimpanzee genomes, but approximately one-third of the CNVs observed in the human genome were unique to our species. (nature.com)
Gene copy-number variation (CNVs), which provides the raw material for the evolution of novel genes, is widespread in natural populations. (biomedcentral.com)
Several lines of evidence suggest that these changes were adaptive: (i) copy-number changes reached high frequency or were fixed in a short time, (ii) many independent populations harbored CNVs spanning the same genes, and (iii) larger average size of CNVs in adapting populations relative to spontaneous CNVs. (biomedcentral.com)
The latter is expected if larger CNVs are more likely to encompass genes under selection for a change in gene dosage. (biomedcentral.com)
In this study, we seek to determine if gene copy-number changes are a common class of genetic change during adaptation and what role, if any, natural selection plays in the maintenance and frequency increase of copy-number variants (CNVs henceforth) in experimental populations. (biomedcentral.com)

The alteration in the gene dosage, which is caused by the loss of a functional allele, is also called allelic insufficiency. (wikipedia.org)
ADGCs supported in Phase 2 of the initiative will be involved in continued efforts to refine and expand the list, as well as developing a rigorous, data-informed approach for selecting patient variants in allelic series from a subset of NPD risk genes. (nih.gov)

A variation of haploinsufficiency exists for mutations in the gene PRPF31, a known cause of autosomal dominant retinitis pigmentosa. (wikipedia.org)
The autosomal recessive form is due to a mutation or deletion of the gene that codes for steroidogenic factor 1 (SF-1) on chromosome 9q33 (OMIM 184757). (medscape.com)
The roles of DAX1 and the undefined autosomal recessive gene in development of the adrenal cortex are not understood. (medscape.com)
The autosomal recessive gene appears to be important in the development of both the fetal adrenal cortex and the definitive adult adrenal cortex because both are hypoplastic in this form of congenital adrenal hypoplasia. (medscape.com)
Cross-species analysis of autosomal gene expression across 12 tissues identified over 2,700 gene-tissue pairs with conserved sex-biased gene expression. (biomedcentral.com)
Furthermore, X chromosome dosage is a major determinant of sex-biased autosomal gene expression, potentially explaining the many disorders where penetrance or expressivity may vary between individuals of different sexes. (biomedcentral.com)
Our data indicate, for the first time, a requirement for MAPK signaling in the developing XY gonad in order to facilitate normal expression of SRY and the downstream testis-determining genes and also suggest that reduced dosage of MAP3K4 may be the cause of a previously described autosomal sex-reversing mutation in the mouse. (plos.org)

Lastly, we elucidated that these nanoparticles could upregulate the downstream genes of Notch signaling, indicating that the payload was viable and successfully altered the genetic downstream effects. (frontiersin.org)

A Gene Selection Task Group within the SSPsyGene Consortium has initiated efforts to prioritize a set of ~100-250 genes associated with NPDs to be interrogated by all Assay and Data Generation Centers (ADGCs), the list of which can be found on the "Resources" tab of the SSPsyGene Consortium website operated by the UC Santa Cruz Data Resource and Administrative Coordinating Center (DRACC). (nih.gov)

Lingxin Zhang, PhD and other researchers in Dr. Weinshilboum's pharmacogenomics laboratory recently identified DNA sequence variants in the genes for ACE2 and TMPRESS2 that might impact clinical outcomes for patients with COVID-19. (medpagetoday.com)

We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants. (plos.org)
In a retrospective study, we apply PVP to the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism, and find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants. (plos.org)
Although currently as many as 26 causal genes are known, there is considerable missing heritability compared to other inherited neuropathies such as Charcot-Marie-Tooth disease. (cmttreatmentreport.com)

In yet another example of a phenotypic link to a chromosomal anomaly, in humans, the duplication of part or all of chromosome 21 has been associated with Down syndrome . (nature.com)
More recently, both aneuploidy and chromosomal translocations have been causally implicated in human cancers . (nature.com)
Additionally, variant annotations to chromosomal positions continue to be updated with the National Center for Biotechnology Information (NCBI) [ 9 ] human genome build as standard. (biomedcentral.com)

There are two wild-type alleles of this gene-a high-expressivity allele and a low-expressivity allele. (wikipedia.org)

The Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes (SSPsyGene) Consortium: Assay and Data Generation Centers (RM1) (RFA-MH-24-145). (nih.gov)
SSPsyGene is designed to provide a collaborative and efficient framework for identifying biological function beyond current small-scale and often ad hoc single gene efforts in order to generate a standardized, experimentally derived, functional catalog of NPD risk genes. (nih.gov)
In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes. (neurotree.org)

additionally, rare variants in SNUPN significantly associated with systolic blood pressure. (biomedcentral.com)

1 The idea that the field of molecular biology needed to move from studying isolated biological molecules towards a broad analysis of large sets of biological molecules was underscored with the completion of the human genome project (HGP) in 2001. (bmj.com)
The presumed gene count of 100,000 for human genome drastically went down to around 20,000 after the completion of Human Genome Project. (tripod.com)

The SSPsyGene Consortium aims to produce a systematic annotation of basic neurobiological function of genes associated with risk for neurodevelopmental and psychiatric disorders (NPDs). (nih.gov)
AceView: gene:dpy-21, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView. (nih.gov)
AceView: gene:him-8, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView. (nih.gov)
Tools like ANNOVAR additionally provide variant annotation to genes and to regions such as conserved regions among species, predicted transcription factor binding sites, and segmental duplication regions. (biomedcentral.com)

In this review, we provide a current overview of the genetic spectrum of hereditary motor neuropathies highlighting recent reports of novel genes and mutations or recent discoveries in the underlying disease mechanisms. (cmttreatmentreport.com)

The haploinsufficiency is caused by the copy-number variation (CNV) of 28 genes led by the deletion of ~1.6 Mb. (wikipedia.org)
This project will include a three-pronged approach to utilizing and studying sex chromosome variation across humans. (grantome.com)
Third, we will study gene expression variation (with an emphasis on X-linked gene expression and X-inactivation) between the sexes, and between populations in the human placenta. (grantome.com)
This work will improve methodology for studying sex-linked variation, provide estimates of sex-biased human demography, and elucidate sex-biased expression in the human placenta. (grantome.com)
There is need to investigate and document genetic variation at loci of pharmacogenetic relevance among different SSA populations since this information could be used to inform drug efficacy, safety and recommended dosage [ Reference Dandara 6 - Reference Masimirembwa and Hasler 8 ]. (cambridge.org)
Structural variation (SV) influences genome organization and contributes to human disease. (biomedcentral.com)
The aim of this study was to determine the genetic variation between and within the different populations of C. caulescens, to determine whether gene flow occur between the different populations and to determine which of the DNA regions included in the study can contribute to the identification of plants from a specific geographical area. (ndltd.org)
A promoter variant c.-242-110delAGTA displayed a significant variation in frequency between both sample sets. (biomedcentral.com)
Luciferase reporter gene assay of the promoter construct bearing this variant did not suggest a variation of expression in the MCF-7 breast cancer cell line, but indicated a reduction of luciferase expression in both the HEK293 and LNCaP cell lines. (biomedcentral.com)

Sex-bias exists in the human genome in DNA content and gene expression. (grantome.com)
Although the field of OMICS is ever expanding (eg, see http://omics.org ), currently five different OMICS fields are well established: genotyping, gene expression profiling, epigenomics, proteomics, and metabolomics. (bmj.com)
Hence, although rare, IAP-induced local heterochromatin spreading into nearby genes may influence expression and, in turn, host fitness. (prolekarniky.cz)
Using these reads we performed gene expression quantification. (biomedcentral.com)
The exon junction complex (EJC) deposited on spliced mRNAs, plays a central role in the post-transcriptional gene regulation and specific gene expression. (nature.com)
The Exon Junction Complex (EJC) plays a central role in post-transcriptional gene expression control. (nature.com)
These observations strongly suggest the implication of EJC in fine-tuning of specific gene expression in different cellular contexts. (nature.com)
In contrast, natural selection for increased gene expression may represent an important mechanism by which duplicate gene copies are maintained in populations [ 14 ]. (biomedcentral.com)
2023) demonstrated successful gene transfer and sustained ARSA expression in a preclinical ARSA-deficient animal model using an AAV-based gene therapy approach. (creativebiomart.net)
Epigenetic regulation of biological functions via gene expression without alterations in the DNA sequence may be an important factor. (cmttreatmentreport.com)
can be based on biological knowledge or predicted variant function, or even be used to integrate gene expression or other omics data. (biomedcentral.com)
Indeed, power improved when gene expression data for FDR-controlled informative weighting of association test p values of genes was used. (biomedcentral.com)
Filters or priors on genes may be derived from methylation or expression data if available in the same individuals. (biomedcentral.com)
The transcription factors accomplish the transformation of the stimulus by activating the gene expression of its target genes. (peptidesforresearch.com)
These data demonstrate that MAP3K4-dependent signalling events are required for normal expression of Sry during testis development, and create a novel entry point into the molecular and cellular mechanisms underlying sex determination in mice and disorders of sexual development in humans. (plos.org)
Analysis of embryonic XY gonads suggests that sex reversal is caused by delayed and reduced expression of the sex-determining gene SRY . (plos.org)
This process is mediated by 2 mutually exclusive programs of gene expression: 1) an undifferentiated program supporting proliferation by stem cells within the basal layer and 2) a differentiation program instructing growth arrest and differentiation-associated programmed cell death in suprabasal layers. (stanford.edu)
Epigenetic control of gene expression lasts through multiple cell divisions without alterations in primary DNA sequence and can occur via mechanisms that include histone modification and DNA methylation. (stanford.edu)
Noncoding RNA sequences can regulate gene expression via interactions with epigenetic and other control mechanisms. (stanford.edu)
The commercial viability of other virus types also continues to be explored, particularly for treatments that require a larger payload, transient expression, or insertion of a gene of interest in the genome. (biopharminternational.com)
Genes with monoallelic expression contribute disproportionately to genetic diversity in humans. (homologyeffects.org)

In Drosophila, the single Nanos gene (Nos) is required for development of the abdomen as well as for germ line maintenance [ 31 , 32 ]. (hindawi.com)
Trans -homolog interactions, such as homolog pairing, are highly structured and associated with gene function in Drosophila cells. (homologyeffects.org)
Here, the authors use haplotype-resolved Hi-C to identify genome-wide trans -homolog interactions in a Drosophila hybrid cell line and investigate complex types of pairing and functional roles. (homologyeffects.org)

We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. (plos.org)

Since most studies are carried out on non-African populations (Asians and Caucasians), a smaller portion of the overall human genome's diversity is interrogated and results from replication studies do not always concur. (cambridge.org)
Due to the high rates of origin of spontaneous duplications and deletions, copy-number changes containing the same genes arose readily in independent populations. (biomedcentral.com)
out of these four variants, one, p.Arg273_Gly276dup, was not detected in control populations and two, p.Pro120Leu and p.Asn173His, were statistically enriched in cases with aniridia or Peters anomaly. (molvis.org)
Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells. (axonmedchem.com)

The latter encompass human skin regenerated on immune deficient mice as well as organotypic constructs with epithelial and stromal cells embedded within architecturally faithful mesenchyma in vitro. (stanford.edu)

According to literally thousands of publications spanning nearly two centuries, the brain is the only organ that is known to regulate body fat mass in humans and other animals-- neither fat tissue itself, nor the insulin-secreting pancreas have the ability to regulate body fat mass as far as we currently know. (blogspot.com)

This diagram shows in true scale the gene on the genome, the mRNAs and the cDNA clones. (nih.gov)

Gene therapies for rare diseases are under threat. (cdc.gov)
Concern is mounting that other gene therapies for rare diseases will meet a similar fate, as might upcoming treatments that rely on the related technique of genome editing, which makes targeted DNA changes. (cdc.gov)
Realising the potential of gene therapies for rare and ultra-rare inherited diseases. (cdc.gov)
From the abstract: 'Rare and ultra-rare diseases have been central to the field of gene therapy since its earliest stage, and we are now witnessing more and more effective treatments entering the clinical realm for patients in need. (cdc.gov)
However, despite promising results across a range of rare diseases, transformative gene therapies may not be available and accessible to patients for non-medical reasons. (cdc.gov)

Caenorhabditis elegans gene dpy-21 , DumPY : shorter than wild-type. (nih.gov)
Caenorhabditis elegans gene him-8 , high Incidence of Males, encoding HIM-8 like family member. (nih.gov)

About 3,000 human genes cannot tolerate loss of one of the two alleles. (wikipedia.org)
As the number and characteristics of such alleles are undetermined, a focussed candidate gene approach based on genes closely interacting with the known susceptibility genes such as BRCA1 and BRCA2 , the two major susceptibility genes identified yet, constitutes a study design of choice to identify rare-moderate-penetrance susceptibility alleles. (biomedcentral.com)

Specifically, it will explore the role of ARSA in lysosomal storage disorders, the development of therapeutic interventions, and the potential applications in enzyme replacement therapy and gene therapy. (creativebiomart.net)
We predict that loss of MAP3K4 or other MAPK components may underlie disorders of sexual development (DSD) in humans as well. (plos.org)
The custom-designed targeted NGS gene panel enabled concurrent variant screening for these disorders. (cdc.gov)

Many methods are currently available to help with the problem of determining causative variant, using information about evolutionary conservation and prediction of the functional consequences of the sequence variant. (plos.org)
Ohno [ 1 ] theorized that newly duplicated genes were freed from the constraints of natural selection, implicating a dominant role of genetic drift in their early evolutionary dynamics. (biomedcentral.com)

Finally, approaches exploiting variant correlations included identity-by-descent mapping and the optimal strategy for joint testing rare and common variants, which was observed to depend on linkage disequilibrium structure. (biomedcentral.com)

An X-linked form (OMIM 300200) is caused by a mutation or deletion of the DAX1 gene (dosage-sensitive sex reversal adrenal hypoplasia congenita critical region of the X chromosome, also called the NR0B1 gene) on the X chromosome. (medscape.com)
X-linked congenital adrenal hypoplasia is due to mutation in, or deletion of, the DAX1 ( AHCH ) gene. (medscape.com)
Somatic mutation signatures based on single nucleotide variants (SNVs) have been previously described. (biomedcentral.com)
We have previously established that the spontaneous, genome-wide rate of gene duplication in C. elegans is two orders of magnitude higher than the point mutation rate [ 8 ]. (biomedcentral.com)
Patients with congenital adrenal hypoplasia due to a mutation or deletion of DAX1 or SF1 (gene name NR5A1) develop hypogonadotropic hypogonadism. (medscape.com)
To have a functional consequence, a mutation does not have to be in the coding region. (tripod.com)
An intronic mutation may well result in a non-functional gene (like the splicing site mutation in CYP21A2 ). (tripod.com)
Individuals with one GRN gene mutation typically do not show signs and symptoms of CLN11 disease, but they may develop another condition called GRN-related frontotemporal lobar degeneration in which cognitive decline begins between a person's forties and sixties. (medlineplus.gov)

This study provides the first evidence that different EJCs can have distinct functions, illuminating EJC-dependent gene regulation. (nature.com)
Several genes of the C-type lectin superfamily, including the rodent NKRP1 family of glycoproteins, are expressed by NK cells and may be involved in the regulation of NK cell function. (thermofisher.com)

Recent studies have explored the use of viral vectors, such as adeno-associated viruses (AAVs), to deliver functional ARSA genes to target cells. (creativebiomart.net)
Viral vectors show promise as a delivery mechanism for gene therapy, but which virus types are commercially viable? (biopharminternational.com)
Several virus types have been studied for use as viral vectors in gene therapy, including adenovirus, lentivirus, retrovirus, and adeno-associated virus (AAV). (biopharminternational.com)

The present study used a new variant of the human HexA α-subunit, μ, incorporating critical sequences from the β-subunit that produce a stable homodimer (HexM) and promote functional interactions with the GM2AP- GM2 complex. (nih.gov)

Lentiviral-mediated gene therapy approaches have been explored to deliver functional ARSA genes to affected cells. (creativebiomart.net)
Identification of the new causes of CMT will facilitate in-depth characterization of the underlying molecular mechanisms of CMT, leading to the establishment of therapeutic approaches such as drug development and gene therapy. (cmttreatmentreport.com)

The following product was used in this experiment: NK1.1 Monoclonal Antibody (PK136), Functional Grade, eBioscience™ from Thermo Fisher Scientific, catalog # 16-5941-82, RRID AB_469159. (thermofisher.com)

On the other hand, eQTL analyses can be used for any genetic variant, but typically require the use of dozens of samples in order to have sufficient individuals in the different genotype classes. (biomedcentral.com)
Ideally, eQTL data on many tissues and many different samples should be available since this would permit eQTL mapping and ASE analyses on rare and low-frequency variants within different cell types. (biomedcentral.com)

reported successful gene therapy in an MLD mouse model, resulting in long-term restoration of ARSA activity and attenuation of disease progression. (creativebiomart.net)

Of these, AAVs have gained much attention as a gene delivery vehicle and are being explored for their commerical viability. (biopharminternational.com)

Particularly for moderate throughput assays, strategies for selecting a subset of genes from the list should be discussed in the context of the chosen assay(s) or readout(s). (nih.gov)
The effect of the promoter variant was further studied by luciferase gene reporter assay in MCF-7, HEK293, HeLa and LNCaP cell lines. (biomedcentral.com)

Further, our research supports the theory that the human dosage-compensation mechanism via X- inactivation, evolved step-wise, in a gene-by-gene specific manner on the X chromosome in response to loss of functional Y-linked genes. (grantome.com)
Type 1 diabetes results from the poorly understood process of islet autoimmunity, which ultimately leads to the loss of functional pancreatic beta cells. (springer.com)

The rates of spontaneous gene duplication and deletion are extraordinarily high and speak to the enormous potential of these structural variants for generating new adaptive variability [ 5 - 10 ]. (biomedcentral.com)

In general, there are two types of gene therapies, namely ex-vivo and in-vivo , Chaudhary points out. (biopharminternational.com)
From the article: 'In the past two years, two gene therapies have been withdrawn from the European market for business reasons after earning regulators' approval. (cdc.gov)

Dose adjustments have been recommended for efavirenz due to genetic variations in CYP2B6 gene, which results in HIV patients in SSA requiring a reduced dose [ Reference Mukonzo 4 , Reference Dhoro 5 ]. (cambridge.org)

In silico programs (ESEfinder, NNSplice, Splice Site Finder and MatInspector) were used to assess the putative impact of the variants identified. (biomedcentral.com)

In a candidate gene study aiming at identifying genetic determinants of breast cancer susceptibility, we undertook the full sequencing of the NBN gene in our cohort of 97 high-risk non- BRCA1 and - BRCA2 breast cancer families, along with 74 healthy unrelated controls, also from the French Canadian population. (biomedcentral.com)
Further analyses will be needed to fully ascertain the exact impact of those variants on breast cancer susceptibility, in particular for variants located in NBN promoter region. (biomedcentral.com)

An example of this is seen in the case of Williams syndrome, a neurodevelopmental disorder caused by the haploinsufficiency of genes at 7q11.23. (wikipedia.org)

We also derived genotypes using the RNA-seq reads and used imputation to infer non-coding variants. (biomedcentral.com)
In a joint analysis on the 1,262 samples with high quality genotypes, we identified cis- eQTLs effects for 8,034 unique genes (at a false discovery rate ≤0.05). (biomedcentral.com)

The forkhead box D3 ( FOXD3 ) gene encodes a forkhead transcription factor that plays an important role in neural crest specification in vertebrates and therefore may be involved in human eye disease. (molvis.org)

Anatomy23

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