Project description:Parent-of-origin dependent expression of alleles, imprinting, has been suggested to impact a substantial proportion of mammalian genes. Its discovery requires allele-specific detection of expressed transcripts, but in some cases detected allelic expression (AE) bias has been interpreted as imprinting without demonstrating compatible transmission patterns and excluding heritable variation. Therefore, we utilized a genome-wide tool exploiting high density genotyping arrays in parallel measurements of genotypes in RNA and DNA to determine AE across the transcriptome in lymphoblastoid cell lines (LCLs) and skin fibroblasts derived from families. To investigate imprinting, transmission patterns were analyzed in 2 LCL trios, 1 LCL 3-generation pedigree and 9 FB trios. To investigate random monoallelic expression, 2 cell lines were treated with three concentrations of 5-azadeoxycytidine (AZA), and one cell line was treated for two time periods.
Project description:Immunoglobulin A Nephropathy (IgAN) is a complex multifactorial disease whose genetic bases remain unknown. Distinct linkage and genome-wide association studies in both familial and sporadic IgAN suggest that there is a strong genetic component in IgAN. In this context, an intriguing role could be ascribed to copy number variants (CNVs) that have been recognized as an important source of genetic variation in humans. Here, we performed a whole-genome screening of CNVs in IgAN patients, their healthy relatives and healthy subjects (HS). A total of 217 individuals consisting of 51 IgAN cases and 166 healthy relatives were included in the initial screening. The high-throughput analysis of structural genetic variations, to find concordant aberrations across classes of samples, identified 178 IgAN-specific aberrations, specifically 114 loss and 64 gain. Several CNVs overlapped with regions evidenced by previous genome-wide genetic studies. Moreover, we found that IgAN patients characterized by deteriorated renal function carried low copy numbers of a CNV in chromosome 3 (chr3_loss:52031010-52260722). This CNV contained the TLR9 gene whose expression significantly correlated with the loss aberration in patients with progressive renal damage. Conversely, IgAN patients with normal renal function had no chr3_loss:52031010-52260722 and the TLR9 mRNA was expressed at the same level as in HS, still maintaining a strong correlation with the CNV. In conclusion, here we performed the first genome-wide CNV study in IgAN identifying some structural variants specific to IgAN patients and providing a collection of new candidate genes and loci that could help to dissect the complex genomic setting of the disease. Moreover, we identified a specific CNV, spanning the TLR9 gene, which could explain the disease severity in IgAN patients. To perform a genome-wide CNV study in IgAN identifying some structural variants specific to IgAN patients and providing a collection of new candidate genes and loci that could help to dissect the complex genomic setting of the disease.
Project description:Here we present genome-wide high-coverage genotyping data on a panel of 75 human samples from Western Balkan region, Europe, that are used in addition to public data in studing the genetic variation of Southern Europe that was sequenced to the avwerage depth of 1X. 70 samples were analysed with the Illumina platform Human660W-Quad v1.0 Genotyping BeadChip and are described herein.
Project description:Here we present genome-wide high-coverage genotyping data on a panel of 85 human samples from Eurasia that are used in addition to public data in studing the genomic context of a 24 kya old DNA sample from Southern Siberia that was sequenced to the avwerage depth of 1X. 85 samples were analysed with the Illumina platforms Human610-Quad v1.0, HumanHap650Yv3 (HumanHap650Yv3_A) and Human660W-Quad v1.0 Genotyping BeadChips and are described herein.
Project description:To carry out population genetics analyses of the Arctic gregion we carried out Illumina Bead-Array-based enotyping on 18 samples from Greenland. 19 samples were analysed with the Illumina platform Human660W-Quad v1.0 Genotyping BeadChip and are described herein.
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.
Project description:Contemporary Jews comprise an aggregate of ethno-religious communities whose worldwide members identify with each other through various shared religious, historical, and cultural traditions1,2. Historical evidence suggests common origins in the Middle East, followed by migrations leading to the establishment of communities of Jews in Europe, Africa, and Asia - in what is termed the Jewish Diaspora3-5. This complex demographic history imposes special challenges in attempting to address the genetic structure of the Jewish people6. While many genetic studies have shed light on Jewish diseases and origins, including those focusing on uniparentally- and biparentally-inherited markers7-16, genome-wide patterns of variation across the vast geographic span of Jewish Diaspora communities and their respective neighbors have yet to be addressed. Here we use high-density bead arrays to genotype individuals from 14 Jewish Diaspora communities, and compare these patterns of genome-wide diversity with those from 69 Old World non-Jewish populations, of which 25 have not been previously reported. These samples were carefully chosen to provide comprehensive comparisons between Jewish and non-Jewish populations in the Diaspora, as well as with non-Jewish populations from the Middle East and North Africa. Principal component and structure-like analyses identify previously unrecognized genetic substructure within the Middle East. Most Jewish samples form a remarkably tight sub-cluster that overlies Druze and Cypriot samples, but not samples from other Levantine populations or paired Diaspora host populations. In contrast, Ethiopian Jews (Beta Israel) and Bene Israel Indian Jews cluster with neighbouring autochthonous populations in Ethiopia and western India, respectively; despite a clear paternal link between the Bene Israel and the Levant. These results cast light on the variegated genetic architecture of the Middle East, and trace the origins of most Jewish Diaspora communities to the Levant. 466 samples are analysed on three different Illumina platforms.
Project description:A genome-wide eQTL analysis was performed in whole blood samples collected from 76 Japanese subjects. RNA microarray analysis was performed for 3 independent samples that were genotyped in a genome-wide scan. The correlations between the genotypes of 534,404 autosomal single nucleotide polymorphisms (SNPs) and the expression levels of 30,465 probes were examined for each sample. The SNP-probe pairs with combined correlation coefficients of all 3 samples corresponding to P < 3.10 × 10-12 (i.e., Bonferroni-corrected P < 0.05) were considered significant. SNP-probe pairs with a high likelihood of cross-hybridization and SNP-in-probe effects were excluded to exclude false positive results. We identified 102 cis-acting and 5 trans-acting eQTL regions. The cis-eQTL regions were widely distributed both upstream and downstream of the gene, as well as within the gene. RNA microarray data obtained from 3 independent samples originally recruited for other studies investigating the gene expression levels in psychiatric disorders were used in the present study. For the purpose of the present analyses, genomic DNA was collected from 24 subjects (13 men and 11 women, mean age [SD] = 39.9 [7.6] years) in sample 1, 24 subjects in sample 2 (12 men and 12 women, 34.1 [11.5] years), and 28 subjects (14 men and 14 women, 41.4 [11.8] years) in sample 3. Some of the subjects had depressive symptoms, but all were physically healthy and without clinically significant systemic disease (e.g., malignant disease, diabetes mellitus, hypertension, renal failure, or endocrine disorders). Subjects were recruited from the outpatient clinic of the National Center of Neurology and Psychiatry Hospital, Tokyo, Japan, through advertisements in free local information magazines or through our website announcement. All the subjects were biologically unrelated Japanese individuals who resided in the same geographical area (western Tokyo). The study protocol was approved by the ethics committee at the National Center of Neurology and Psychiatry, Japan. Written informed consent was obtained from every subject after the study was explained to them. Venous blood was collected between 1100 and 1200 h in PAXgene tubes (Qiagen, Valencia) from each subject and was incubated at room temperature for 24 h for RNA stabilization. RNA was extracted from whole blood according to the manufacturer’s guidelines by using the PAXgene Blood RNA System Kit (PreAnalytix GmbH, Hombrechtikon, Switzerland). The RNA was quantified by optical density readings at A260nm by using the NanoDrop ND-1000 (Thermo Scientific, Rockford). Gene expression analysis was performed using Agilent Human Genome 4 × 44 K arrays (Agilent Technologies, Santa Clara). Raw signal data for each of the 3 independent samples were analyzed separately by the GeneSpring GX software (Agilent Technologies). Data were filtered according to the expression level for quality control to eliminate genes that were below the 20th percentile threshold. The expression value of each gene was normalized to the median expression value of all genes in each chip. A total of 30,465 probes were included in the analysis. Genomic DNA was obtained from venous blood samples. Genotyping was performed by Riken Genesis (Yokohama, Japan) using the Illumina HumanOmni1-Quad BeadChip (Illumina, Inc., San Diego). A total of 713,495 autosomal SNPs were assessed for quality using the PLINK v1.07 software. All SNPs with a call rate below 95%, a deviation from Hardy-Weinberg equilibrium at an error level of P < 0.001, or a minor allele frequency of less than 10% were excluded. The remaining 534,404 SNPs were used for further analysis.
Project description:Human clear cell renal cell carcinoma (ccRCC) is a common cancer of the kidney. We applied an integrated approach to identify important factors that influence carcinogenesis in ccRCC. 33 frozen ccRCC samples were subject to copy number analysis. The data was analyzed to identify factors affecting tumorigenesis. The samples were also stained for HIF-1alpha and HIF-2alpha expression. The tumors were subtyped based on HIF expression and investigated for differences in genetic aberrations.
Project description:Hispanic/Latino populations possess a complex genetic structure that reflects recent admixture among and potentially ancient substructure within Native American, European, and West African source populations. Here, we quantify genome-wide patterns of SNP and haplotype variation among 100 individuals with ancestry from Ecuador, Colombia, Puerto Rico, and the Dominican Republic genotyped using Illumina technology. To investigate variations of continental ancestry between different Hispanic/Latino groups (using self-reported country-specific identification of individual, both parents, and all four grandparents) and within them from healthy controls represented in the New York Health Project Biorepository. Genotyped on the Illumina 610-Quad, which is identical to HumanHap550-v3 SNPs plus an additional ~60,000 SNPs for CNV, no CNV data is provided or was analyzed.