Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA209050 | ENA |
REPOSITORIES: ENA
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Project description:The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work. Gene expression data was determined of peripheral blood samples (n=705) from InChianti cohort.
2013-06-21 | E-GEOD-48152 | biostudies-arrayexpress
Project description:The identification of multiple signals at individual loci could explain additional phenotypic variance ('missing heritability') of common traits, and help identify causal genes. We examined gene expression levels as a model trait because of the large number of strong genetic effects acting in cis. Using expression profiles from 613 individuals, we performed genome-wide single nucleotide polymorphism (SNP) analyses to identify cis-expression quantitative trait loci (eQTLs), and conditional analysis to identify second signals. We examined patterns of association when accounting for multiple SNPs at a locus and when including additional SNPs from the 1000 Genomes Project. We identified 1298 cis-eQTLs at an approximate false discovery rate 0.01, of which 118 (9%) showed evidence of a second independent signal. For this subset of 118 traits, accounting for two signals resulted in an average 31% increase in phenotypic variance explained (Wilcoxon P< 0.0001). The association of SNPs with cis gene expression could increase, stay similar or decrease in significance when accounting for linkage disequilibrium with second signals at the same locus. Pairs of SNPs increasing in significance tended to have gene expression increasing alleles on opposite haplotypes, whereas pairs of SNPs decreasing in significance tended to have gene expression increasing alleles on the same haplotypes. Adding data from the 1000 Genomes Project showed that apparently independent signals could be potentially explained by a single association signal. Our results show that accounting for multiple variants at a locus will increase the variance explained in a substantial fraction of loci, but that allelic heterogeneity will be difficult to define without resequencing loci and functional work.
2013-06-21 | GSE48152 | GEO
Project description:BubR1 allelic effects drive phenotypic heterogeneity in MVA progeria syndrom
| PRJEB33810 | ENA
Project description:Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To establish whether PPGL phenotypic differences reflect a MAX-mediated mechanism and opposing influences of HIF2M-NM-1 and HIF1M-NM-1, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2M-NM-1, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1M-NM-1 has opposing actions to HIF2M-NM-1. These model systems explain the features observed in PPGLs due to mutations of MAX and other PPGL susceptibility genes. 88 samples (primary pheochromocytoma (PCC)/paraganglioma tumors) were hybridized onto a cDNA microarray in order to investigate possible heterogeneity within these tumors. This series of tumors is an expansion of GSE19422 that includes nine additional tumors to examine the role of MAX mutations in PCC/PGL.
2014-09-18 | E-GEOD-51081 | biostudies-arrayexpress
Project description:Phenotypic variability is a hallmark of diseases involving chromosome gains and losses, such as Down Syndrome and cancer. Allelic variances have been thought to be the sole cause of this heterogeneity. Here, we systematically examine the consequences of gaining and losing single or multiple chromosomes to show that the aneuploid state causes non-genetic phenotypic variability. Yeast cell populations harboring the same defined aneuploidy exhibit heterogeneity in cell cycle progression and response to environmental perturbations, which we show to be partly due to gene copy number imbalances. Thus, subtle changes in gene expression severely impact the robustness of biological networks and cause alternate behaviors when they occur at a large scale. Because trisomic mice also exhibit variable phenotypes, we further propose that non-genetic individuality is a universal characteristic of the aneuploid state that could contribute to variability in presentation and treatment responses of diseases caused by aneuploidy.
2017-04-10 | PXD006009 | Pride
Project description:Pistacia chinensis Bunge is known as dioecious, but we have found wild monoecious individuals. In order to screen the candidate genes which may influence the sex expression or floral phenotypic differences of P. chinensis, the inflorescence buds for different sex types associated with the sex differentiation were selected and tested for small RNA sequencing. Sex-specific differentially expressed small RNA were discovered, combined with real-time PCR data, the regulation patterns of various sex types were first revealed. Our study represents the first detailed analysis of small RNA sequencing, providing more clues for understanding the mechanism of sex determination on P. chinensis.
2020-01-01 | GSE128023 | GEO
Project description:Analysis of genomic methylation differences between day workers and shift workers. We hypothesized that there would be differences in methylation patterns between day workers and shift workers, and that some of these differences may explain the association between long-term shift work and breast cancer. The array provides methylation data on more than 27,000 CpG sites spread across the genome.
2011-09-03 | GSE31770 | GEO
Project description:A major goal of genetics research is to elucidate mechanisms explaining how genetic variation contributes to phenotypic variation. The genetic variants identified in genome-wide association studies (GWASs) generally explain only a small proportion of heritability of phenotypic traits, the so-called missing heritability problem. Recent evidence suggests that additional common variants beyond lead GWAS variants contribute to phenotypic variation; however, their mechanistic underpinnings generally remain unexplored. Herein, we undertake a study of haplotype-specific mechanisms of gene regulation at 8p23.1 in the human genome, a region associated with a number of complex diseases. The FAM167A-BLK locus in this region has been consistently found in the genome-wide association studies (GWASs) of systemic lupus erythematosus (SLE) in all major ancestries. Our haplotype-specific chromatin interaction (Hi-C) experiments, allele-specific enhancer activity measurements, genetic analyses, and epigenome editing experiments revealed that: (1) haplotype-specific long-range chromatin interactions are prevalent in 8p23.1; (2) BLK promoter and cis-regulatory elements cooperatively interact with haplotype-specificity; (3) genetic variants at distal regulatory elements are allele-specific modifiers of the promoter variants at FAM167A-BLK; (4) the BLK promoter interacts with and, as an enhancer-like promoter, regulates FAM167A expression and (5) local allele-specific enhancer activities are influenced by global haplotype structure due to chromatin looping. Although SLE causal variants at the FAM167A-BLK locus are thought to reside in the BLK promoter region, our results reveal that genetic variants at distal regulatory elements modulate promoter activity, changing BLK and FAM167A gene expression and disease risk. Our results suggest that global haplotype-specific 3-dimensional chromatin looping architecture has a strong influence on local allelic BLK and FAM167A gene expression, providing mechanistic details for how regional variants controlling the BLK promoter may influence disease risk.
2022-09-07 | GSE211246 | GEO
Project description:Analysis of genomic methylation differences between day workers and shift workers. We hypothesized that there would be differences in methylation patterns between day workers and shift workers, and that some of these differences may explain the association between long-term shift work and breast cancer. The array provides methylation data on more than 27,000 CpG sites spread across the genome. Bisulfite-converted DNA from 10 day workers and 10 shift workers were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2.
2011-09-02 | E-GEOD-31770 | biostudies-arrayexpress
Project description:BubR1 allelic effects drive phenotypic heterogeneity in MVA progeria syndrome [10 month old RNA-seq]
| PRJNA556413 | ENA