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Individual-specific and allele-specific chromatin signatures in diverse human populations

ABSTRACT: This dataset contains DNase-seq data and CTCF ChIP-seq data for 6 lymphoblastoid cell lines. There are 3 cell lines from a YRI trio and 3 lines from a CEU trio (HapMap GM19238, GM19239, GM 19240, GM12891, GM12892, GM12878). For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

ORGANISM(S): Homo sapiens

PROVIDER: GSE19622 | GEO | 2010/03/15

REPOSITORIES: GEO

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Individual-specific and allele-specific chromatin signatures in diverse human populations

Project description:This dataset contains DNase-seq data and CTCF ChIP-seq data for 6 lymphoblastoid cell lines. There are 3 cell lines from a YRI trio and 3 lines from a CEU trio (HapMap GM19238, GM19239, GM 19240, GM12891, GM12892, GM12878). For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf DNase-seq and ChIP-seq data from each of the 6 cell lines.

2010-03-15 | E-GEOD-19622 | biostudies-arrayexpress

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Project description:Large inter-individual variance has been observed in sensitivity to drugs. To comprehensively decipher the genetic contribution to these variations in drug susceptibility, we present a genome-wide model utilizing human lymphoblastoid cell lines from the International HapMap consortium, of which extensive genotypic information is available, to identify genetic variants that contribute to chemotherapeutic agent-induced cytotoxicity. Our model integrated genotype, gene expression and sensitivity of HapMap cell lines to drugs. Cell lines derived from 30 trios of European descent (CEU) and 30 trios of African descent (YRI) were utilized. Cell growth inhibition at increasing concentrations of etoposide for 72 h was determined using alamarBlue® assay. Gene expression on 176 HapMap cell lines (87 CEU and 89 YRI) was determined using the Affymetrix GeneChip® Human Exon 1.0ST Array. We evaluated associations between genotype and cytotoxicity, genotype and gene expression and correlated gene expression of the identified candidates with cytotoxicity. The analysis identified 63 genetic variants that contribute to etoposide-induced toxicity through their effect on gene expression. These include genes that may play a role in cancer (AGPAT2, IL1B and WNT5B) and genes not yet known to be associated with sensitivity to etoposide. This unbiased method can be used to elucidate genetic variants contributing to a wide range of cellular phenotypes induced by chemotherapeutic agents. Keywords: exon array

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Identification of Genetic Variants Contributing to Cisplatin-Induced Cytotoxicity using a Genome-wide Approach

Project description:Cisplatin, a platinating agent commonly used in treating several cancers is associated with nephrotoxicity, neurotoxicity and ototoxicity that have hindered its utility. To gain a better understanding of the genetic variants associated with cisplatin induced toxicity, we present a step-wise approach integrating genotypes, gene expression and sensitivity of HapMap cell lines to cisplatin. Cell lines derived from 30 trios of European descent (CEU) and 30 trios of African descent (YRI) were utilized to develop a preclinical model to identify genetic variants and gene expression that contribute to cisplatin induced cytotoxicity in two different populations. Cytotoxicity was determined as cell growth inhibition at increasing concentrations of cisplatin for 48 h. Gene expression on 176 HapMap cell lines (87 CEU and 89 YRI) was determined using the Affymetrix GeneChip® Human Exon 1.0 ST Array. We identified 6, 2 and 9 representative SNPs that contribute to cisplatin-induced cytotoxicity through their effects on 8, 2 and 16 gene expressions in the combined, CEPH and Yoruban populations, respectively. These genetic variants contribute to 27, 29 and 45% of the overall variation in cell sensitivity to cisplatin in the combined, CEPH and Yoruban populations, respectively. Our whole genome approach can be used to elucidate expression quantitative trait loci contributing to a wide range of cellular phenotypes. Keywords: exon array

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Transcription profiling of human samples show variation in african americans with genetic ancestry at most expressed genes

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