Identification of Common Genetic Variants that Account for Transcript Isoform Variation between Human Populations
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE9703 | GEO | 2009/03/23
SECONDARY ACCESSION(S): PRJNA103609
REPOSITORIES: GEO
Similar Datasets
Project description:In addition to the differences between populations in transcriptional and translational regulation of genes, alternative pre-mRNA splicing (AS) is also likely to play an important role in regulating gene expression and generating variation in mRNA and protein isoforms. Recently, the genetic contribution to transcript isoform variation has been reported in individuals of recent European descent. We report here results of an investigation of the differences in AS patterns between human populations. AS patterns in 176 HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry were evaluated using the Affymetrix GeneChip Human Exon 1.0 ST Array. A variety of biological processes such as immune response and mRNA metabolic process were found to be enriched among the differentially spliced genes. The differentially spliced genes also include some involved in human diseases that have different prevalence or susceptibility between populations. The genetic contribution to the population differences in transcript isoform variation was then evaluated by a genome-wide association using the HapMap genotypic data on single nucleotide polymorphisms (SNPs). The results suggest that local and distant genetic variants account for a substantial fraction of the observed transcript isoform variation between human populations. Exon level expression on 176 HapMap cell lines.
2010-08-19 | E-GEOD-9703 | biostudies-arrayexpress
Project description:Elucidating cytosine modification difference between human populations can enhance our understanding of ethnic specificity in complex traits such as disease predisposition and drug response. In this study, cytosine modification levels in 133 HapMap lymphoblastoid cell lines (LCLs) derived from individuals of European or African ancestry were profiled using the Illumina HumanMethylation450 BeadChip. Approximately 13% of the analyzed CpG sites showed differential modification between the two populations at false discovery rate (FDR) of 1%. CpG sites with greater modification levels in European descents were enriched in the proximal regulatory regions, while those greater in African descents were biased toward gene bodies. More than half of the detected population-specific cytosine modifications could be explained by genetic variation. A substantial proportion of local modification quantitative trait loci (mQTL) exhibited population-specific effects, suggesting that genetic epistasis and/or genotype × environment interaction could be common. Distinct inter-individual correlations were observed between gene expression and cytosine modifications in both proximal promoters and gene bodies, demonstrating a regulatory role of inter-individual variation in cytosine modification. Furthermore, a number of SNPs (single nucleotide polymorphisms) previously identified for complex traits with known racial disparities could be annotated as mQTLs for population-specific CpGs. Our findings revealed abundant population-specific cytosine modifications and the underlying genetic basis, as well as the relatively independent contribution of genetic and epigenetic variations to population differences in gene expression. 60 HapMap CEU and 73 HapMap YRI samples from Coriell Insitute were profiled for cytosine modification levels.
2013-07-01 | E-GEOD-39672 | biostudies-arrayexpress
Project description:We have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternate splice site usage, intron retention), differential 5’ UTR (initiation of transcription) usage, and differential 3’ UTR (alternative polyadenylation) usage. These results demonstrate that the regulatory effects of genetic variation in a normal human population are drastically more complex than previously observed. This additional layer of molecular diversity may account for natural phenotypic variation and disease susceptibility. Keywords: Comparative genomic hybridiation within the CEU HapMap population
2008-01-13 | GSE9372 | GEO
Project description:Gene expression is a complex quantitative trait partially regulated by genetic variation in DNA sequence. Population differences in gene expression could contribute to some of the observed differences in susceptibility to common diseases and responses to drug treatments. We characterize gene expression in the full set of HapMap lymphoblastoid cell lines derived from individuals of European and African ancestry for 9,156 transcript clusters (gene-level) evaluated using the Affymetrix GeneChip® Human Exon 1.0 ST Array. Gene expression was found to differ significantly between these samples for 383 transcript clusters. Biological processes including ribosome biogenesis and antimicrobial humoral response were found to be enriched in these differential genes, suggesting their possible roles in contributing to the population differences at a higher level than mRNA expression and the population differences in response to environmental information. Genome-wide association studies for local or distant genetic variants that correlate with the differentially expressed genes enabled identification of significant associations with one or more single nucleotide polymorphisms (SNPs), consistent with the hypothesis that genetic factors and not simply population identity or other characteristics (age of cell lines, length of culture etc.) contribute to differences in gene expression in these samples. Our results provided a comprehensive view of the genes differentially expressed between populations and the enriched biological processes involved in these genes. We also provided an evaluation of the contribution of genetic variation and non-genetic factors to the population differences in gene expression. Keywords: exon array
2008-05-08 | GSE7851 | GEO
Project description:Identification of Common Genetic Variants that Account for Transcript Isoform Variation between Human Populations
| PRJNA103609 | ENA
Project description:Elucidating cytosine modification difference between human populations can enhance our understanding of ethnic specificity in complex traits such as disease predisposition and drug response. In this study, cytosine modification levels in 133 HapMap lymphoblastoid cell lines (LCLs) derived from individuals of European or African ancestry were profiled using the Illumina HumanMethylation450 BeadChip. Approximately 13% of the analyzed CpG sites showed differential modification between the two populations at false discovery rate (FDR) of 1%. CpG sites with greater modification levels in European descents were enriched in the proximal regulatory regions, while those greater in African descents were biased toward gene bodies. More than half of the detected population-specific cytosine modifications could be explained by genetic variation. A substantial proportion of local modification quantitative trait loci (mQTL) exhibited population-specific effects, suggesting that genetic epistasis and/or genotype × environment interaction could be common. Distinct inter-individual correlations were observed between gene expression and cytosine modifications in both proximal promoters and gene bodies, demonstrating a regulatory role of inter-individual variation in cytosine modification. Furthermore, a number of SNPs (single nucleotide polymorphisms) previously identified for complex traits with known racial disparities could be annotated as mQTLs for population-specific CpGs. Our findings revealed abundant population-specific cytosine modifications and the underlying genetic basis, as well as the relatively independent contribution of genetic and epigenetic variations to population differences in gene expression.
2013-07-01 | GSE39672 | GEO
Project description:Background: Differences in levels of gene expression among individuals are an important source of phenotypic variation within populations. Recent microarray studies have revealed that expression variation is abundant in many species, including Drosophila melanogaster. However, previous expression surveys in this species generally focused on a small number of laboratory strains established from derived populations. Thus, these studies were not ideal for population genetic analyses. Results: We surveyed gene expression variation in adult males of 16 D. melanogaster strains from two natural populations, including an ancestral African population and a derived European population. Levels of expression polymorphism were nearly equal in the two populations, but a higher number of differences was detected when comparing strains between populations. Expression variation was greatest for genes associated with few molecular functions or biological processes, as well as those expressed predominantly in males. Our analysis also identified genes that differed in expression level between the European and African populations, which may be candidates for adaptive regulatory evolution. Genes involved in flight musculature and fatty acid metabolism were over-represented in the list of candidates. Conclusions: Overall, stabilizing selection appears to be the major force governing gene expression variation within populations. However, positive selection may be responsible for much of the between-population expression divergence. The nature of the genes identified to differ in expression between populations may reveal which traits were important for local adaptation to the European and African environments. Keywords: Natural variation
2008-01-21 | GSE8843 | GEO
Project description:Background: Differences in levels of gene expression among individuals are an important source of phenotypic variation within populations. Recent microarray studies have revealed that expression variation is abundant in many species, including Drosophila melanogaster. However, previous expression surveys in this species generally focused on a small number of laboratory strains established from derived populations. Thus, these studies were not ideal for population genetic analyses. Results: We surveyed gene expression variation in adult males of 16 D. melanogaster strains from two natural populations, including an ancestral African population and a derived European population. Levels of expression polymorphism were nearly equal in the two populations, but a higher number of differences was detected when comparing strains between populations. Expression variation was greatest for genes associated with few molecular functions or biological processes, as well as those expressed predominantly in males. Our analysis also identified genes that differed in expression level between the European and African populations, which may be candidates for adaptive regulatory evolution. Genes involved in flight musculature and fatty acid metabolism were over-represented in the list of candidates. Conclusions: Overall, stabilizing selection appears to be the major force governing gene expression variation within populations. However, positive selection may be responsible for much of the between-population expression divergence. The nature of the genes identified to differ in expression between populations may reveal which traits were important for local adaptation to the European and African environments. We used dual channel microarrays to compare genome-wide expression profiles in adult males from 16 inbred strains derived from two natural populations. In total 80 hybidizations were performed including dye-swaps. The hybridization scheme consisted of a balanced loop design, which allowed an unbiased comparison of relative expression levels within and between populations.
2008-01-20 | E-GEOD-8843 | biostudies-arrayexpress
Project description:Humans show remarkable variation in susceptibility to infectious diseases as well as chronic inflammatory and autoimmune disorders. This heterogeneity arises partially from variation in the immune response, which is responsible for preventing and controlling infection. To better understand the major factors driving antiviral immune response differences, we used single-cell RNA-sequencing to measure the effects of genetic ancestry and cis-regulatory variation on the transcriptional response to influenza infection in various immune cell types in 90 European and African American individuals. We show that monocytes are the most responsive to infection but that all cell types engage a conserved, type I IFN response, which is stronger in European individuals. Further, we detect directional, polygenic differences in expression phenotypes between populations that are under cis-genetic control and show that recent positive selection has acted on putatively causal risk loci associated with common autoimmune disorders. Our findings establish genetic ancestry and common cis-regulatory variants as important determinants governing the antiviral immune response, thus improving our understanding of the factors that contribute to differences in infectious and complex disease susceptibility.
2021-11-26 | GSE162632 | GEO
Project description:Ethnic differences in human DNA methylation have been shown for a number of CpG sites, but the genome-wide patterns and extent of these differences are unknown. In addition, whether the genetic control of polymorphic DNA methylation is population-specific has not been investigated. Here we measure DNA methylation near the transcription start sites of over 14,000 genes in 180 cell lines derived from one African and one European population. We find population-specific patterns of DNA methylation at over a third of all genes. Furthermore, although the methylation at over a thousand CpG sites is heritable, these heritabilities are also distinctly different between populations, suggesting extensive divergence in the genetic control of DNA methylation. In support of this, genetic mapping of DNA methylation reveals that there is also little overlap in genetic associations between populations. This population-specificity is supported by the patterns of DNA methylation in several hundred brain samples, suggesting it holds in vivo and across tissues. These results suggest that DNA methylation is highly divergent between populations, and that this divergence may be due in large part to complex epistasis or gene x environment interactions. Genomic DNA from 180 lymphoblastoid cell lines were bisulphite converted and hybridized, along with 8 additional technical replicates, to the Illumina Infinium HumanMethylation27 Beadchip v1.2 for genome-wide DNA methylation profiling. The cell lines were derived from two HapMap populations: 'CEPH (Utah residents with ancestry from northern and western Europe)' (CEU) and 'Yoruba in Ibadan, Nigeria' (YRI).
2012-01-30 | E-GEOD-27146 | biostudies-arrayexpress