Mapping of Hepatic Expression Quantitative Trait Loci (eQTLs) in a Han Chinese Population
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Zhiqiang Li
PROVIDER: E-GEOD-53792 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Elucidating the genetic basis underlying the variation in hepatic gene expression is of importance to understand disease etiology and drug metabolism variances. To date, no genome-wide eQTL analysis has been conducted in the Han Chinese, the largest ethnic group in the world. We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue (n=64). Normal (non-diseased) liver tissues were previously collected from 64 Chinese donors who provided informed consent. All samples were stored frozen at -80℃ from collection until processing for RNA and DNA extraction. DNA /Total RNA of the human liver tissue samples were extracted by using the RNA/DNA Mini Kit (Qiagen, Hilden, Germany).each RNA sample were labeled and hybridized to the One-Color Agilent 60-mer Whole Human Genome Microarray (G4112F, GPL4133) at the Agilent Microarray Facility of Shanghai genomePilot Technology, Inc. The genome-wide scan was performed using the Affymetrix Genome-Wide Human SNP Array 6.0. We tested all expression traits for their associations with each of the QC passed SNPs using PLINK's assoc function for quantitative traits, which correlates allele dosage with changes in the trait.
2015-01-02 | E-GEOD-53790 | biostudies-arrayexpress
Project description:Elucidating the genetic basis underlying the variation in hepatic gene expression is of importance to understand disease etiology and drug metabolism variances. To date, no genome-wide eQTL analysis has been conducted in the Han Chinese, the largest ethnic group in the world. We performed a genome-wide eQTL mapping in a set of Han Chinese liver tissue (n=64). Normal (non-diseased) liver tissues were previously collected from 64 Chinese donors who provided informed consent. All samples were stored frozen at -80M-bM-^DM-^C from collection until processing for RNA and DNA extraction. DNA /Total RNA of the human liver tissue samples were extracted by using the RNA/DNA Mini Kit (Qiagen, Hilden, Germany).each RNA sample were labeled and hybridized to the One-Color Agilent 60-mer Whole Human Genome Microarray (G4112F, GPL4133) at the Agilent Microarray Facility of Shanghai genomePilot Technology, Inc. The genome-wide scan was performed using the Affymetrix Genome-Wide Human SNP Array 6.0. We tested all expression traits for their associations with each of the QC passed SNPs using PLINK's assoc function for quantitative traits, which correlates allele dosage with changes in the trait.
2015-01-02 | E-GEOD-53791 | biostudies-arrayexpress
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2013-12-13 | E-GEOD-53261 | biostudies-arrayexpress
Project description:Sakha M-bM-^@M-^S an area connecting South and Northeast Siberia M-bM-^@M-^S is significant for understanding the history of peopling of Northeast Eurasia and the Americas. Previous studies have shown a genetic contiguity between Siberia and East Asia and the key role of South Siberia in the colonization of Siberia. We report the results of a high-resolution phylogenetic analysis of 701 mtDNAs and 318 Y chromosomes from five native populations of Sakha (Yakuts, Evenks, Evens, Yukaghirs and Dolgans) and of the analysis of more than 500,000 autosomal SNPs of 758 individuals from 55 populations, including 40 previously unpublished samples from Siberia. Phylogenetically terminal clades of East Asian mtDNA haplogroups C and D and Y-chromosome haplogroups N1c, N1b and C3, constituting the core of the gene pool of the native populations from Sakha, connect Sakha and South Siberia. Analysis of autosomal SNP data confirms the genetic continuity between Sakha and South Siberia. Maternal lineages D5a2a2, C4a1c, C4a2, C5b1b and the Yakut-specific STR sub-clade of Y-chromosome haplogroup N1c can be linked to a migration of Yakut ancestors, while the paternal lineage C3c was most likely carried to Sakha by the expansion of the Tungusic people. MtDNA haplogroups Z1a1b and Z1a3, present in Yukaghirs, Evens and Dolgans, show traces of different and probably more ancient migration(s). Analysis of both haploid loci and autosomal SNP data revealed only minor genetic components shared between Sakha and the extreme Northeast Siberia. Although the major part of West Eurasian maternal and paternal lineages in Sakha could originate from recent admixture with East Europeans, mtDNA haplogroups H8, H20a and HV1a1a, as well as Y-chromosome haplogroup J, more probably reflect an ancient gene flow from West Eurasia through Central Asia and South Siberia. Our high-resolution phylogenetic dissection of mtDNA and Y-chromosome haplogroups as well as analysis of autosomal SNP data suggests that Sakha was colonized by repeated expansions from South Siberia with minor gene flow from the Lower Amur/Southern Okhotsk region and/or Kamchatka. The minor West Eurasian component in Sakha attests to both recent and ongoing admixture with East Europeans and an ancient gene flow from West Eurasia. 40 samples were analysed with the Illumina platform Human660W-Quad v1.0 and are described herein.
2013-06-26 | E-GEOD-46828 | biostudies-arrayexpress
Project description:Background DNA methylation has long been known to play an essential role in the epigenetic regulation of gene expression and other cellular functions, and has been in some cases linked to genetic variation. While its presence near the transcription start site of a gene has been associated with reduced expression, the variation in methylation levels across individuals, its environmental or genetic causes, and its association with gene expression remain poorly understood. Results We report the joint analysis of sequence variants, gene expression and DNA methylation in primary fibroblast samples derived from a set of 62 unrelated individuals. Approximately 2% of the most variable CpG sites are mappable in cis to sequence variation, usually within 5kb. However, only 5% of those mappable CpG sites also have methylation levels that correlate in cis with a gene's expression level. Methylation and gene expression are often correlated but not always in the expected direction (negative for promoter CpGs, positive for gene body CpGs). Population-level correlation between methylation and expression is strongest in a subset of developmentally significant genes, including all four HOX clusters. The presence and sign of this correlation are best predicted using specific histone marks or DNase hypersensitivity rather than position of the CpG site with respect to the gene, showing that other epigenetic markers are necessary to interpret downstream effects of individual methylation variants. Conclusion Our results indicate strong relationships between gene expression and DNA methylation in untransformed adult human fibroblasts, with considerable involvement of chromatin features and relatively modest involvement of sequence variation. 98 human skin fibroblast samples obtained from Coriell and McGill Cellbank, genotypes were obtained using Illumina HumanOmni 1M Beadchips.
2013-12-11 | E-GEOD-52442 | biostudies-arrayexpress
Project description:Renal cell carcinoma (RCC) exhibits some unusual features and genes commonly mutated in cancer are rarely mutated in clear-cell RCC (ccRCC), the most common type. The most prevalent genetic alteration in ccRCC is the inactivation of the tumor suppressor gene VHL. Using whole-genome and exome sequencing we discovered BAP1 as a novel tumor suppressor in ccRCC that shows little overlap with mutations in PBRM1, another recent tumor suppressor. Whereas VHL was mutated in 81% of the patients (142/176), PBRM1 was lost in 58% and BAP1 in 15% of the patients analyzed. All these tumor suppressor genes are located in chromosome 3p, which is partially or completely lost in most ccRCC patients. However, BAP1 but not PBRM1 loss was associated with higher Fuhrman grade and, therefore, poorer outcome. Xenograft tumors (tumorgrafts) implanted orthotopically in mice retained >92% of mutations and exhibited similar DNA copy number alterations to corresponding primary tumors. Thus, after inactivation of VHL, the acquisition of a mutation in BAP1 or PBRM1 defines a different program that might alter the fate of the patient. Our results establish the foundation for an integrated pathological and molecular genetic classification of about 70% of ccRCC patients, paving the way for subtype-specific treatments exploiting genetic vulnerabilities. The genomic DNA of clear-cell renal cell carcinoma (ccRCC) primary tumors, tumors growing in immunodeficient mice (tumorgrafts), and normal samples were labeled and hybridized to Affymetrix SNP arrays 6.0.
2012-06-09 | E-GEOD-25540 | biostudies-arrayexpress
Project description:Melanoma cell lines were genotyped to evaluate copy number differences between nodular melanoma (NM) and superficial spreading melanoma (SSM). Cell lines were also evaluated for copy number alterations in the SKP2/p27 axis. Affymetrix SNP arrays were performed according to manufacturer's instructions using DNA extracted from 18 melanoma cell lines and 4 melanocyte controls. Affymetrix SNP6.0 Array data for melanoma cell lines Copy number analysis of Affymetrix SNP 6.0 arrays was performed on 18 melanoma cell lines including 2 primary superficial spreading melanoma, 2 primary nodular melanoma, 2 metastatic nodular melanoma, and 12 metastatic cell lines. Four melanocyte control lines were also evaluated including 2 immortalized melanocyte cell lines (Hermes 1 and 2B) and 2 normal melanocyte lines cultured from neonatal foreskin (HEM-N and HEM-LP) that were used to construct the baseline for copy number analysis.
2010-10-21 | E-GEOD-22305 | biostudies-arrayexpress
Project description:X chromosome inactivation (XCI) is a dosage compensation mechanism in female cells to regulate X-linked gene expression. We report here that subcultures from established lines of female hESCs displayed variations (0-100%) in the expression of XCI markers such as XIST RNA coating and enrichment of histone H3 lysine 27 trimethylation (H3K27me3) on inactive X chromosome. Surprisingly, regardless of the presence or absence of XCI markers in different cultures, all female hESCs we examined (H7, H9, and HSF6 cells) exhibit a mono-allelic expression pattern for a majority of X-linked genes. Our results suggest that these established female hESCs have completed XCI during the process of derivation and/or propagation, and the XCI pattern of lines we investigated is already non-random. However, XIST gene expression in subsets of female hESCs is unstable and subject to epigenetic silencing through DNA methylation. Concomitant with the loss of XCI markers including XIST expression and H3K27me3, approximately 12% of X-linked CpG islands become hypomethylated and a subset of previously silenced X-linked alleles are reactivated, resulting a significant elevation of gene expression dosage. Because changes in dosage compensation of X-linked genes could impair somatic cell function, we propose that XCI status should be routinely checked in subcultures of female hESCs, with cultures displaying XCI markers better suited for use in regenerative medicine. Keywords: Genotyping, gene expression and DNA methylation We used Affymetrix Genotyping array for looking for X-linked SNPs with HSF6, H7 and H9 genomic DNA, Agilent Gene expression array for comparing gene expression patten changes between HSF6 hESCs with X-inactiation and HSF6 hESCs without X-inactivation (3 repeats). Finally, mDIP-Chip method was used to detect X-linked CpG island methylation changes differences between hESCs with X-inactivation and hESCs without X-inactivation using Agilent CpG island array (3 repeats, and one of them has dye swap)
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2010-06-10 | E-GEOD-21478 | biostudies-arrayexpress
Project description:The Caucasus, inhabited by modern humans since the Early Upper Paleolithic and known for its linguistic diversity, is considered to be important for understanding human dispersals and genetic diversity in Eurasia. We report a synthesis of autosomal, Y chromosome, and mitochondrial DNA (mtDNA) variation in populations from all major subregions and linguistic phyla of the area. Autosomal genome variation in the Caucasus reveals significant genetic uniformity among its ethnically and linguistically diverse populations and is consistent with predominantly Near/Middle Eastern origin of the Caucasians, with minor external impacts. In contrast to autosomal and mtDNA variation, signals of regional Y chromosome founder effects distinguish the eastern from western North Caucasians. Genetic discontinuity between the North Caucasus and the East European Plain contrasts with continuity through Anatolia and the Balkans, suggesting major routes of ancient gene flows and admixture. 204 samples were analysed with the Illumina platform Human610-Quad v 1.0 and are described herein.
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