• Objective-Susceptibility to atherosclerosis is genetically complex, and modifier genes that do not operate via traditional risk factors are largely unknown. (scite.ai)
  • Methods and Results-We previously identified atherosclerosis susceptibility QTL (Athsq1) on chromosome 4 acting independently of systemic risk factors. (scite.ai)
  • No prior knowledge of gene or gene effects is necessary, but the genetic locus must have sufficient impact on the disease susceptibility to be detectable. (scialert.net)
  • CDKN2A appears to be a low penetrance breast cancer susceptibility gene in Poland. (bmj.com)
  • There is continuing interest in identifying low penetrance genes that are associated with increased susceptibility to common types of cancer. (bmj.com)
  • The CDKN2A (OMIM 600160) gene is a tumour suppressor gene that is involved in susceptibility to malignant melanoma 1 and has also been implicated in familial pancreatic cancer. (bmj.com)
  • Helsinki, "The role of chromosomes 2q33, 7q32 and 19q13 in multiple sclerosis susceptibility", Oct. 2009. (helsinki.fi)
  • The association of the 4q25 susceptibility variant for atrial fibrillation with stroke is limited to stroke of cardioembolic etiology. (nature.com)
  • The current research is aimed at assessing the correlation between two functional GAS5 variants (rs145204276 and rs55829688) and susceptibility to IS in a Han Chinese population. (hindawi.com)
  • In addition, a number of different genetic determinants of IS risk have been identified in genome-wide association studies, with single-nucleotide polymorphisms (SNPs) in 9p21, PITX2, HDAC9, ABO, NINJ2, ALDH2, and TSPAN2, all being linked with stroke susceptibility [ 2 ]. (hindawi.com)
  • These SNPs, however, are still thought to account for less than half of all genetic susceptibility to IS, with a number of yet to be discovered genes also contributing to the development of IS. (hindawi.com)
  • Nature Genetics) of the first new susceptibility genes for 17 years defined a pivotal moment in Alzheimer's genetics research. (cardiff.ac.uk)
  • Genome-wide association studies (GWAS) in Iceland, Australia, New Zealand, and Finland have indicated a possible susceptibility locus on chromosome 2 although complete agreement does not exist as to the specific location. (mhmedical.com)
  • These diseases, which include cancers, coronary heart disease, schizophrenia, autism and multiple sclerosis, arise from complex interactions between environmental factors and variation in several different genes. (biomedcentral.com)
  • The chromosome 9p21.3 coronary heart disease risk allele is associated with altered gene expression in normal heart and vascular tissues. (cdc.gov)
  • Following on from the achievements in molecular studies of monogenic disorders, recent studies have used strategies of hypothesis-free fine mapping of genes and loci to identify underlying factors in common complex diseases with major impacts on public health. (biomedcentral.com)
  • Until recently, detection of the genes underlying these diseases met with only limited success, but the past two years have witnessed the identification of more than 100 well established loci. (biomedcentral.com)
  • A genetic aetiology has been identified in up to 20% of apparently "sporadic" and 60% of familial ALS cases, in which two or more family members are clinically affected, with at least 16 genes and genetic loci implicated in ALS pathogenesis. (acnr.co.uk)
  • A recent genome-wide association study of intracranial aneurysms in Finnish, Dutch and Japanese cohorts totaling 5,891 cases and 14,181 controls identified three new loci strongly associated with intracranial aneurysms on chromosomes 18q11.2 and 10q24.32, and replicated two previously found loci on chromosomes 8q11.23-q12.1 and 9p21.3. (biomedcentral.com)
  • However, other loci have been reported from GWAS of populations including 10q21.3, 2p25.1, 9p21, 2p11.2, and 4q34 reflecting the multifactorial nature of pre-eclampsia and limitations of GWAS applications. (mhmedical.com)
  • Over 100 pathogenic mutations in the NOTCH3 gene, an evolutionarily highly conserved transmembrane receptor protein regulating cell fate, 4 are known to almost always lead to an odd number of cysteine residues in one of the 34 epidermal growth factor like repeats in the extracellular domain of the Notch3 protein. (bmj.com)
  • Mutations in some genes cause rare forms of T2DM, giving additional support for the genetic roles in the aetiology of the disease. (scialert.net)
  • It is possible that missense variants of genes for which truncating mutations are clearly pathogenic may also be deleterious, but with reduced penetrance. (bmj.com)
  • Mutations in the gene in coding BRCA1- associated protein 1 (BAP1) have been shown to accelerate asbestos induced mesothelioma and is associated with a syndrome consisting of familial cancers in humans including malignant Mesothelioma and uveal melanomas. (standardofcare.com)
  • Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. (nature.com)
  • Conducting studies in mice with atherosclerosis, the researchers showed that loss of a candidate gene at this locus leads to impaired "efferocytosis" - from the Latin for "take to the grave" - the process by which dead or necrotic cells are removed. (stanford.edu)
  • In other words, a commonly inherited genetic variant, which is found in 20 percent of the population, contributes to the development of coronary artery disease (also known as coronary atherosclerosis) by stimulating the accumulation of necrotic debris within the evolving plaque. (stanford.edu)
  • The association of ACE I/D gene polymorphism with severe carotid atherosclerosis in patients undergoing carotid endarterectomy. (cdc.gov)
  • 7][8][9] Attempts to identify genes directly underlying coronary artery disease (CAD)/ myocardial infarct (MI) were first pursued through linkage studies of families enriched for disease 10 -14 and large-scale association studies. (scite.ai)
  • 2011) identified a polymorphic hexanucleotide repeat (GGGGCC) located between the noncoding exons 1a and 1b of the C9ORF72 gene. (coriell.org)
  • The expanded repeat is located in the promoter region of C9ORF72 transcript variant 1 and in intron 1 of transcript variants 2 and 3. (coriell.org)
  • Tissue from affected individuals showed reduced or absent mRNA levels of C9ORF72 variants 1 and 3 compared to nonrepeat carriers, consistent with a loss-of-function mechanism. (coriell.org)
  • Large expansions of a non-coding GGGGCC-repeat in the first intron of the C9orf72 gene are a common cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). (nature.com)
  • Large expansions of the non-coding GGGGCC-repeat in the first intron of the C9orf72 gene have been recently demonstrated to cause ALS and FTD 5 , 6 . (nature.com)
  • A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). (nih.gov)
  • Risk variants for atrial fibrillation on chromosome 4q25 associate with ischemic stroke. (nature.com)
  • A sequence variant in ZFHX3 on 16q22 associates with atrial fibrillation and ischemic stroke. (nature.com)
  • Alternatively, the presence of multiple layers of epigenetic regulation may in fact protect imprinted genes from such perturbation. (prolekarniky.cz)
  • We demonstrate that, despite the functional mono-allelicism of imprinted genes and their unique mechanisms of epigenetic dosage control, imprinted genes as a class are neither more susceptible nor protected from expression perturbation induced by maternal undernutrition in either the F1 or the F2 generation compared to other genes. (prolekarniky.cz)
  • We and others have hypothesised that a compromised in utero environment may impinge upon the epigenetic apparatus with lasting consequences for gene expression and development. (prolekarniky.cz)
  • Inducing CIN causes widespread epigenetic dysregulation, and chromosomes that transit in micronuclei experience heritable abnormalities in their accessibility long after they have been reincorporated into the primary nucleus. (escholarship.org)
  • Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. (escholarship.org)
  • 2008). FISH studies are useful adjuncts to complete chromosome studies, particularly when following an abnormal clone, assessing relapse and progression, or when material is inadequate for chromosomal analysis. (ohsu.edu)
  • Alternate splicing results in multiple transcript variants. (nih.gov)
  • New approaches, including identification of causal variants, rare variants and copy number variants, such as insertions and deletions, may improve genetic risk prediction for SAH and intracranial aneurysms. (biomedcentral.com)
  • Overexpression of LRP12, a gene contained within an 8q22 amplicon identified by high-resolution array CGH analysis of oral squamous cell carcinomas. (nih.gov)
  • In their extreme form, these changes will meet criteria for behavioral-variant frontotemporal dementia (bvFTD). (medscape.com)
  • It is becoming increasingly apparent that studies locating genes underlying complex phenotypes also benefit from the study of samples from homogeneous populations with a limited number of founders - 'founder populations' (Table 1 ). (biomedcentral.com)
  • OBJECTIVES- Genome-wide association studies have dramatically increased the number of common genetic variants that are robustly associated with type 2 diabetes. (diabetesjournals.org)
  • Here, we assess the ability of 18 confirmed type 2 diabetes variants to differentiate between type 2 diabetic case and control subjects. (diabetesjournals.org)
  • Using a new and powerful technology in the form of a genome-wide chip that genotypes up to hundreds of thousands of SNPs, Genome-Wide Association Studies (GWAS) have recently led to the discovery of a group of novel genes that were reproducibly associated with T2DM risk. (scialert.net)
  • Despite extensive molecular genetics investigations, non specific reproducibly genetic variants associated with CAD were found. (biomedcentral.com)
  • Widely studied CETP variants is a silent base change called the Thermobius aquaticus IB (TaqIB) affecting the 277th nucleotide in the first intron of the CETP gene [ 18 ]. (biomedcentral.com)
  • AD and Parkinson's disease, ALS, schizophrenia) and complex statistical analyses (e.g. gene-wide/burden, pathway analyses). (cardiff.ac.uk)
  • This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. (escholarship.org)
  • We then combined the search algorithm with system-level kinetic modeling, requiring the construction and characterization of 73 variants to build a sequence-expression-activity map (SEAMAP) for a biosynthesis pathway. (omictools.com)
  • Using model predictions, we designed and characterized 47 additional pathway variants to navigate its activity space, find optimal expression regions with desired activity response curves, and relieve rate-limiting steps in metabolism. (omictools.com)
  • There are several approaches to this problem, including the use of chip based single nucleotide polymorphism (SNP) arrays to interrogate a large number of genes simultaneously, and preselecting candidate genes of interest. (bmj.com)
  • The sex-specific association of Met62Ile gene polymorphism in P-selectin glycoprotein ligand (PSGL-1) with carotid plaque presence: preliminary study. (cdc.gov)
  • The relationship between TaqIB gene polymorphism and the LMCAD was independent of lipid profile, with the exception of apolipoprotein A. (biomedcentral.com)
  • Relationship between CAD risk genotype in the chromosome 9p21 locus and gene expression. (wikipedia.org)
  • Early studies used the candidate gene approach to identify rare genetic variants contributing to traditional risk factors including plasma levels of LDL/VLDL, HDL, lipoprotein (a), homocysteine, and blood pressure. (scite.ai)
  • T2DM is a complex trait where common genetic variants having modest individual effects act together and interact with environmental factors to modulate the risk of the disease. (scialert.net)
  • If you were born with genetic variation at the 9p21 locus, your risk of heart disease is elevated, though we haven't understood why. (stanford.edu)
  • You can be a non-smoker, be thin, have low blood pressure, and still be at risk for a heart attack if you were born with this variant. (stanford.edu)
  • Our study supports a model wherein the rs145204276 variant in the GAS5 lncRNA is associated with IS risk, thus representing a potentially viable biomarker for IS prevention and treatment. (hindawi.com)
  • Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. (mdpi.com)
  • The AUC for age, BMI, and sex was 0.78, and adding the genetic risk variants only marginally increased this to 0.80. (diabetesjournals.org)
  • Two genes encoding putative internalin proteins were chosen for further study. (omictools.com)
  • More than 10% of patients with malignant mesothelioma have germline variants. (standardofcare.com)
  • Earlier studies using a candidate gene approach, family linkage studies and gene expression profiling uncovered a number of T2DM genes, but the genetic basis of common T2DM remained unknown. (scialert.net)
  • First, molecular events in T2DM pathogenesis have been examined directly by testing the role of sequence variants of specific candidate genes. (scialert.net)
  • The candidate gene approach focuses on the search for an association between T2DM and sequence variants in or near biologically defined candidate genes which have been chosen based on their known physiological function. (scialert.net)
  • To overcome the shortcomings of the candidate gene studies, investigators have applied a genome-wide linkage scan strategy in which regularly spaced markers are traced in families and sibling pairs for segregation with T2DM. (scialert.net)
  • Candidate genes for cancers at a particular site may be selected because they are known to predispose to malignancies in other organs, or because they are mutated somatically in the cells from the cancer of the interest. (bmj.com)
  • Further refinement with transcription-targeted candidate genes initially derived from androgenic (fetus-free) placentas and applied to whole genome screening successfully further refined a pre-eclampsia-linked site to 2q22. (mhmedical.com)
  • Upregulated in decidua from pre-eclamptic women, a candidate gene within this region, activin ( ACVR2) was given the highest priority as a possible gene for pre-eclampsia. (mhmedical.com)
  • Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. (omictools.com)
  • Advances in our knowledge about the workings of genes and their variants coupled with technological advances in analysing the genome along with improved bioinformatics has enabled greater understanding of the underlying molecular aetiology of ischaemic stroke. (bmj.com)
  • Leeper, a physician and assistant professor of vascular surgery, and colleagues Yoko Kojima, MD, Tom Quertermous , MD, and others set out to discover why genetic variation at the chromosome 9p21 location has been repeatedly identified as the most important commonly inherited DNA sequence for a wide range of cardiovascular diseases including stroke, heart attacks and aneurysms. (stanford.edu)
  • We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. (nature.com)
  • Changes in DNA methylation and histone modifications at putative regulatory regions correlating with the altered expression of genes implicated in phenotypic development have been observed in a number of animal models of early life compromise [3] - [8] . (prolekarniky.cz)
  • Well characterized human populations provide excellent study samples for many different genetic investigations, ranging from genome-wide association studies to the characterization of interactions between genes and the environment. (biomedcentral.com)
  • This term emerged out of the standardized longitudinal observation of pre-symptomatic carriers of autosomal dominant genes for ALS within the pre-fALS study, a natural history observational study. (medscape.com)
  • Approximately 20 genes consistently associated with T2DM mainly implicate pancreatic β-cell function in the pathogenesis of T2DM. (scialert.net)
  • The continuing work by deCODE genetics on 50 common diseases is sure to result in a slew of additional gene findings and help to characterize the allelic spectrum of disease-predisposing variants. (biomedcentral.com)
  • Imprinted genes, a class of functionally mono-allelic genes critical for early growth and metabolic axis development, have been proposed to be uniquely susceptible to environmental change. (prolekarniky.cz)
  • Abundance of LRP12 C-rs9694676 allelic promoter variant in epilepsy-associated gangliogliomas. (nih.gov)
  • CONCLUSION: Regardless of histology and location, the molecular landscape of mesothelioma primarily consists of inactivating alterations in tumor suppressor genes, with enrichment of certain alterations in distinct subsets (eg, MTAP loss in nonepithelioid tumors). (bvsalud.org)
  • As a result of this differential cell cycle-regulatory gene expression by HDAC inhibition, the retinoblastoma protein retains a transcriptional repression of its downstream target genes required for S phase entry. (cret-signal.com)
  • Here we show that missegregation of mitotic chromosomes, their sequestration in micronuclei 5,6 and subsequent rupture of the micronuclear envelope 7 profoundly disrupt normal histone post-translational modifications (PTMs), a phenomenon conserved across humans and mice, as well as in cancer and non-transformed cells. (escholarship.org)
  • Variants in the GAS5 promoter region have been reported to be linked to mutiple diseases. (hindawi.com)
  • Samples of individuals from genetically isolated populations, or 'population isolates', have already proved immensely useful in the identification of rare recessive disease genes. (biomedcentral.com)
  • This, among other benefits of a geographically isolated population, has enabled the identification by means of linkage, and more recently by genome-wide association (GWA) studies, of an impressive number of variants contributing to the development of common/complex disease [ 5 ]. (biomedcentral.com)
  • A common missense variant of the CDKN2A gene (A148T) predisposes to malignant melanoma in Poland. (bmj.com)
  • GAS5 is found on chromosome 1q25.1, with the gene containing 12 exons across a 4.087 kb region, coding for 29 different GAS5 splicing variants [ 11 ]. (hindawi.com)
  • It is located within the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster, in the antisense direction. (wikipedia.org)
  • In Poland, a single missense variant of CDKN2A (an alanine to threonine substitution at codon 148: A148T) is present in approximately 3% of the general population. (bmj.com)
  • CDKN2A (p16) / CEP 9 to detect loss of 9p21 region. (ohsu.edu)
  • Unbiased investigation of these alternative hypotheses requires assessment of imprinted gene expression in the context of the response of the whole transcriptome to environmental assault. (prolekarniky.cz)
  • Such genes are only detectable in isolated populations with a limited number of founders, where rare disease alleles are enriched, thus resulting in homozygote individuals affected by the disease. (biomedcentral.com)
  • However, protein levels of these variants were similar to controls, and analysis of patient frontal cortex and spinal cord tissue showed that the transcribed expanded GGGGCC repeat formed nuclear RNA foci, suggesting a gain-of-function mechanism. (coriell.org)
  • This gene encodes a member of the low-density lipoprotein receptor related protein family. (nih.gov)
  • The product of this gene is a transmembrane protein that is differentially expressed in many cancer cells. (nih.gov)
  • Microtubule-associated protein tau encoded by the MAPT gene binds to microtubules and is important for maintaining neuronal morphology and function. (biomedcentral.com)
  • Once the abnormal gene products are better understood, specific medical treatments may emerge. (medscape.com)
  • Assessment of the genetic effects of polymorphisms in the osteoprotegerin gene, TNFRSF11B, on serum osteoprotegerin levels and carotid plaque vulnerability. (cdc.gov)
  • The DNA of 471 subjects [133 subjects with angiographically documented left main coronary artery disease (LMCAD), 241 subjects with more peripheral coronary artery disease (MPCAD) and 97 subjects self reported healthy (Controls)] was analyzed for the frequency of TaqIB and I405V polymorphisms in the gene coding CETP. (biomedcentral.com)
  • Thus the studies evaluating the influence of CETP gene polymorphisms in humans are essential. (biomedcentral.com)
  • What is striking about her group's findings is that the genes identified show patterns of relationship, which implicate novel disease mechanisms, including immunity, endocytosis, lipid transport and ubiquination. (cardiff.ac.uk)
  • The detection of genes underlying common complex diseases might not always need large global population samples. (biomedcentral.com)
  • Interestingly, comparative mapping revealed that the Athsq1 congenic interval contains the mouse region homologous to a widely-replicated CHD locus on human chromosome 9p21. (scite.ai)
  • Joint principal investigator of the study Dr. Jamie Engert, a researcher in cardiovascular diseases at the Research Institute of the McGill University Health Centre (RI-MUHC) and associate member in the Department of Human Genetics at McGill University, and colleagues investigated the effect of diet on the 9p21 gene - the strongest genetic marker for heart disease - in more than 27,000 people. (worldhealth.net)