Polymorphic cis- and trans-regulation of human gene expression
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE16921 | GEO | 2010/09/20
SECONDARY ACCESSION(S): PRJNA117631
REPOSITORIES: GEO
Similar Datasets
Project description:Expression levels of human genes vary extensive among individuals. Gene expression determines cell function and characteristics thus this variation likely contributes to phenotypic variation. Genetic studies have shown that there is a heritable component to gene expression variation, and have identified genomic regions that contain polymorphic regulators. However, most of these regions are quite large, and few regulators have been identified. In this genetic of gene expression study, we used a large sample to search the genome for polymorphic regulators that influence gene expression, and followed up the results with deep sequencing of transcriptomes and molecular analyses. Key word(s): Transcriptome Analysis genetics of gene expression study, 41 Coriell cell line samples examined.
2010-09-19 | E-GEOD-16921 | biostudies-arrayexpress
Project description:Goal: To identify copy number variation in normal individuals using high density, non-polymorphic oligonucleotide probes Background DNA sequence diversity within the human genome may be more greatly affected by copy number variations (CNVs) than single nucleotide polymorphisms (SNPs). Although the importance of CNVs in genome wide association studies (GWAS) is becoming widely accepted, the optimal methods for identifying these variants are still under evaluation. We have previously reported a comprehensive view of CNVs in the HapMap DNA collection using high density 500K EA (Early Access) SNP genotyping arrays which revealed greater than 1,000 CNVs ranging in size from 1kb to over 3Mb. Although the arrays used most commonly for GWAS predominantly interrogate SNPs, CNV identification and detection does not necessarily require the use of DNA probes centered on polymorphic nucleotides and may even be hindered by the dependence on a successful SNP genotyping assay. Results In this study, we have designed and evaluated a high density array predicated on the use of non-polymorphic oligonucleotide probes for CNV detection. This approach effectively uncouples copy number detection from SNP genotyping and thus has the potential to significantly improve probe coverage for genome-wide CNV identification. This array, in conjunction with PCR-based, complexity-reduced DNA target, queries over 1.3M independent NspI restriction enzyme fragments in the 200bp to 1100bp size range, which is a several fold increase in marker density as compared to the 500K EA array. In addition, a novel algorithm was developed and validated to extract CNV regions and boundaries. Conclusions Using a well-characterized pair of DNA samples, close to 200 CNVs were identified, of which nearly 50% appear novel yet were independently validated using quantitative PCR. The results indicate that non-polymorphic probes provide a robust approach for CNV identification, and the increasing precision of CNV boundary delineation should allow a more complete analysis of their genomic organization. A set of five genomic DNA samples containing different numbers of X chromosomes (1X to 5X sample set, including NA15510 and NA10851) were hybridized to Nsp copy number (CN) arrays in triplicate to evaluate detection of copy number variation using high density, non-polymorphic oligonucleotide probes. 6 Hapmap samples were hybridized to Nsp CN arrays to evaluate Mendelian inheritance of CNVs.
2008-04-24 | E-GEOD-9053 | biostudies-arrayexpress
Project description:Polymorphic integrations of endogenous retroviruses (ERVs) have been previously detected in mouse and human genomes. While most are inert, a subset is capable of influencing the activity of the host genes. However, the molecular mechanism underlying how such elements affect the epigenome and transcriptome and their roles in driving intra-specific variation remain unclear. Here, utilizing wildtype murine embryonic stem cells (mESCs) derived from distinct genetic backgrounds, we discovered a polymorphic MMERGLN element capable of regulating H3K27ac enrichment, transcription and higher-order chromatin structure of neighboring loci. We demonstrated that this polymorphic element enhanced the neighboring Klhdc4 gene’s expression in cis, which in turn altered activity of downstream stress response genes. The results suggest that the polymorphic ERV-derived cis-regulatory element contribute to strain-specific phenotypes from particular stimuli. Moreover, we identified thousands of potential polymorphic ERVs in mESCs from both strains and illustrated their potential to regulate nearby histone modifications and transcription. Overall, our findings show the mechanism of how polymorphic ERVs can shape the epigenome and transcriptional networks that give rise to phenotypic divergence between individuals.
2021-09-22 | GSE165214 | GEO
Project description:Goal: To identify copy number variation in normal individuals using high density, non-polymorphic oligonucleotide probes Background DNA sequence diversity within the human genome may be more greatly affected by copy number variations (CNVs) than single nucleotide polymorphisms (SNPs). Although the importance of CNVs in genome wide association studies (GWAS) is becoming widely accepted, the optimal methods for identifying these variants are still under evaluation. We have previously reported a comprehensive view of CNVs in the HapMap DNA collection using high density 500K EA (Early Access) SNP genotyping arrays which revealed greater than 1,000 CNVs ranging in size from 1kb to over 3Mb. Although the arrays used most commonly for GWAS predominantly interrogate SNPs, CNV identification and detection does not necessarily require the use of DNA probes centered on polymorphic nucleotides and may even be hindered by the dependence on a successful SNP genotyping assay. Results In this study, we have designed and evaluated a high density array predicated on the use of non-polymorphic oligonucleotide probes for CNV detection. This approach effectively uncouples copy number detection from SNP genotyping and thus has the potential to significantly improve probe coverage for genome-wide CNV identification. This array, in conjunction with PCR-based, complexity-reduced DNA target, queries over 1.3M independent NspI restriction enzyme fragments in the 200bp to 1100bp size range, which is a several fold increase in marker density as compared to the 500K EA array. In addition, a novel algorithm was developed and validated to extract CNV regions and boundaries. Conclusions Using a well-characterized pair of DNA samples, close to 200 CNVs were identified, of which nearly 50% appear novel yet were independently validated using quantitative PCR. The results indicate that non-polymorphic probes provide a robust approach for CNV identification, and the increasing precision of CNV boundary delineation should allow a more complete analysis of their genomic organization. Keywords: Copy number variation (CNV) detection
2008-04-24 | GSE9053 | GEO
Project description:see publication, arrays from 4 XXY genotypes containing polymorphic Y chromosomes
2010-10-02 | GSE23612 | GEO
Project description:Polymorphic immune mechanisms regulate commensal repertoire
| PRJNA562711 | ENA
Project description:Environmental influences such as infections and dietary changes strongly affect a host’s microbiota. In the steady state, however, host genetics may influence the microbiota composition, as suggested by the greater similarity between the microbiomes of identical twin pairs compared to non-identical twins. Understanding the role of polymorphic mechanisms in regulating the commensal communities is complicated by the variability of human genomes and microbiomes, and by microbial sensitivity to the environment. Animal studies allow genetic modifications, but are also sensitive to influences known as ‘cage’ or ‘legacy’ effects. Here, we analyzed ex-germ-free mice of various genetic backgrounds, including immunodeficient and Major Histocompatibility Complex (MHC)-congenic strains repopulated with identical input microbiota. We found that the host’s genetic polymorphic mechanisms did indeed affect the gut microbiome and that both innate (e.g. anti-microbial peptides, complement, pentraxins and enzymes affecting microbial survival), as well as adaptive (both MHC-dependent and MHC-independent) pathways influenced the microbiota. These polymorphic mechanisms regulated only a limited number of microbial lineages (independently of their abundance). In addition, our comparative analyses suggested that some microbes might benefit from the specific immune responses that they elicit.
2019-08-29 | GSE136572 | GEO
Project description:see publication, arrays from 4 XXY genotypes containing polymorphic Y chromosomes Dye swaps, loop design.
2010-10-02 | E-GEOD-23612 | biostudies-arrayexpress
Project description:We report the transcriptome data produced from isogenic polymorphic p53 codon 72 iPSCs under doxorubicin treatment. By inserting BAC DNA into one allele of the heterozygous polymorphic p53 codon 72, each clone expressed a p53 protein encoding P72 or R72 from another allele in which it was not inserted. The transcriptional regulation of p53 target genes was compared between the isogenic lines under doxorubicin treatment.
2021-09-10 | GSE183668 | GEO
Project description:The maternal and paternal copies of the genome are both required for mammalian development and this is primarily due to imprinted genes, those that are mono-allelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilisation. There are a large number of germline DMRs that have not yet been associated with imprinting and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs, specifically in the human placenta, and investigated the dynamics of imprinted DMRs during development in somatic and extra-embryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 116 human tissue samples, publically available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. 43 known and 101 novel imprinted DMRs were identified in the human placenta, by comparing methylation between diandric and digynic triploids and female and male gametes. 72 novel DMRs showed a pattern consistent with placental-specific imprinting and this mono-allelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation specifically in placenta. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation
2015-12-22 | GSE74738 | GEO