Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA103609 | ENA |
REPOSITORIES: ENA
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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: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.
2009-03-23 | GSE9703 | GEO
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 varies between individuals and corresponds to a key step linking genotypes to phenotypes. Regulation of transcript and protein abundances can affect the final phenotypes and has been related to many human diseases. However, our knowledge regarding the species-wide genetic control of protein abundance, including its dependency on transcript levels, is very limited. Here, we have determined quantitative proteomes of a large population of 942 diverse natural Saccharomyces cerevisiae yeast isolates. We found that mRNA and protein abundances are weakly correlated at the population gene level (r = 0.165). While the protein co-expression network recapitulates the major biological functions, differential expression patterns reveal proteomic signatures related to specific populations, mainly domesticated. Most importantly, comprehensive genetic association analyses highlight that genetic variants associated with variation in protein (pQTL) and transcript (eQTL) levels poorly overlap (3.6%), with mostly common local QTL. Our results demonstrate that transcriptome and proteome are clearly two distinct layers of regulation, governed by distinct genetic bases in natural populations, and therefore highlight the importance of integrating these different levels of gene expression to better understand the genotype-phenotype relationship. This submission contains the raw files for the wild isolates collection, the library used for the analysis and the corresponding DIA-NN report and associated files.
2024-04-30 | PXD044523 | Pride
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:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
2023-01-21 | GSE125714 | GEO
Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
2023-01-21 | GSE125713 | GEO
Project description:Genome Wides Association Studies (GWAS) have identified tens of thousands of associations between human genetic variation and common disease. Despite the abundance of GWAS associations, functional identification and characterization of causative variants and effector genes remains a challenging prospect. Human erythropoiesis provides a highly tractable model system for the development of tools for GWAS analysis. Using the Human Umbilical Derived Erythroid Progenitor 2 (HUDEP-2) cell line we have modelled the effects of two variants associated with red blood cell traits using CRISPR/Cas9 facilitated HDR editing.
2023-01-21 | GSE125712 | GEO
Project description:Deciphering the impact of genetic variants on gene regulation is fundamental to understanding human disease. Although gene regulation often involves long-range interactions, it is unknown to what extent non-coding genetic variants influence distal molecular phenotypes. Here, we integrate chromatin profiling for three histone marks in lymphoblastoid cell lines (LCLs) from 75 sequenced individuals with LCL-specific Hi-C and ChIA-PET-based chromatin contact maps to uncover one of the largest collections of local and distal histone quantitative trait loci (hQTLs). Distal QTLs are enriched within topologically associated domains and exhibit largely concordant variation of chromatin state coordinated by proximal and distal non-coding genetic variants. Histone QTLs are enriched for common variants associated with autoimmune diseases and enable identification of putative target genes of disease-associated variants from genome-wide association studies. These analyses provide insights into how genetic variation can affect human disease phenotypes by coordinated changes in chromatin at interacting regulatory elements.
2015-08-20 | GSE62742 | GEO
Project description:The alteration of gene expression due to variations in the sequences of transcriptional regulatory elements has been a focus of substantial inquiry in humans and model organisms. However, less is known about the extent to which natural variation contributes to post-transcriptional regulation. Allelic Expression Imbalance(AEI) is a classical approach for studying the association of specific haplotypes with relative changes in transcript abundance. Here, we benchmarked a new TRAP based approach to associate genetic variation with transcript occupancy on ribosomes in specific cell types, to determine if it will allow examination of Allelic Translation Imbalance(ATI), and Allelic Translation Efficiency Imbalance, using as a test case mouse astrocytes in vivo. We show that most changes of the mRNA levels on ribosomes were reflected in transcript abundance, though ~1.5% of transcripts have variants that clearly alter loading onto ribosomes orthogonally to transcript levels. These variants were often in conserved residues and altered sequences known to regulate translation such as upstream ORFs, PolyA sites, and predicted miRNA binding sites. Such variants were also common in transcripts showing altered abundance, suggesting some genetic regulation of gene expression may function through post-transcriptional mechanisms. Overall, our work shows that naturally occurring genetic variants can impact ribosome occupancy in astrocytes in vivo and suggests that mechanisms may also play a role in genetic contributions to disease.
2023-08-17 | GSE156414 | GEO