GWAS for drug response in patients with OCD
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Hidehiro Umehara
PROVIDER: E-GEOD-76611 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Hypoplastic left heart syndrome (HLHS) is a heterogeneous, lethal combination of congenital malformations that result in a heart unable to sustain systemic circulation. The genetic determinants of this disorder are largely unknown. Evidence of copy number variants (CNVs) contributing to the genetic etiology of HLHS and other congenital heart defects (CHDs) has been mounting. However, the functional effects of such CNVs have not been examined, particularly in cases where the variant of interest is found in only a single patient. Initially whole-genome SNP microarrays were employed to detect CNVs in two patient cohorts (N = 70 total) predominantly diagnosed with some form of nonsyndromic HLHS. We discovered 16 rare variants adjacent to or overlapping 20 genes associated with cardiovascular or premature lethality phenotypes in mouse knockout models. Fifteen of the 16 variants were identified in separate patients, suggestive of a private mutation model of disease. We evaluated the impact of selected variants on the expression of nine of these genes through quantitative PCR on cDNA derived from patient heart tissue. Four genes displayed significantly altered expression in patients with an overlapping or proximal CNV verses patients without such CNVs. Thus, rare and private genomic imbalances perturb transcription of genes affecting cardiogenesis in a subset of nonsyndromic HLHS patients. Some of these genes influence extracellular matrix structure, cardiac neural crest development, and coronary vascularization. A total of 70 samples from CHD patients, mostly with nonsyndromic HLHS, yielded SNP genotypes and probe intensity ratios of sufficient quality for CNV identification. Two classes of CNV detection algorithms (HMM and CBS) were employed. After identification, concordant entries were subjected to selection criteria based on rarity and gene content, which produced putative candidate genes for follow-up experiments.
2015-12-10 | E-GEOD-66032 | biostudies-arrayexpress
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a mother to her child. The chromothripsis in the mothers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two mothers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one child with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy individuals strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. Here, we analyzed one patient-parent-mother's parents quintet to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients.
2015-01-31 | E-GEOD-65451 | biostudies-arrayexpress
Project description:The diagnosis of myelodysplastic syndromes (MDS) remains problematic due to the subjective nature of morphological assessment. The reported high frequency of somatic mutations and increased structural variants by array-based cytogenetics have provided potential objective markers of disease however this has been complicated by reports of similar abnormalities in the healthy population. We aimed to identify distinguishing features between those with early MDS and reported healthy individuals by characterising 69 patients who, following a non-diagnostic marrow, developed progressive dysplasia or acute myeloid leukaemia (AML). Targeted sequencing and array based cytogenetics identified a driver mutation and/or structural variant in 91% (63/69) of pre-diagnostic samples with the mutational spectrum mirroring that in the MDS population. When compared with the reported healthy population the mutations detected had significantly greater median variant allele fraction (40% vs 9-10%) and occurred more commonly with additional mutations (≥2 mutations 64% vs. 8%). Furthermore mutational analysis identified a high-risk group of patients with shorter time to disease progression and poorer overall survival. The mutational features in our cohort are distinct from those seen in the healthy population and, even in the absence of definitive disease, can predict outcome. Early detection may allow consideration of intervention in poor risk patients. We performed array based cytogenetics using HumanCytoSNP-12 (Illumina) on 69 patients diagnosed with acute myeloid leukaemia or myelodysplastic syndrome who had a previously non-diagnostic sample. SNP array analysis was performed on all diagnostic samples. In those with a documented abnormality, SNP-A was performed on the corresponding pre-diagnostic sample (n=32).
2015-09-17 | E-GEOD-73074 | biostudies-arrayexpress
Project description:The goal of the present study was to identify genetic variants that are associated with drug response of OCD patients.
2016-01-08 | GSE76611 | GEO
Project description:The search for novel oncogenes is important because these could be the target of future specific anticancer therapies. In the present work, we report the identification of novel amplified genes in lung cancer. In order to find out novel amplified genes in lung cancer, we aligned the gene expression data of 69 human lung tumors according to the position of transcripts in the human genome and searched for clusters of overexpressed genes. We found a cluster in chromosomes 13q34 and 11q12 with gene overexpression in four of these tumors. Then, we performed FISH analysis in these amplicons, which clearly evidenced the presence of high level copy number in these chromosomal regions. We performed SNP arrays-based in the tumors that carried gene amplification. The results clearly evidenced the presence of a high level copy number amplicon in these specimens. We determined the genomic copy number profile of four squamous cell carcinoma (SCC) tumours using a SNP array, the Illumina Infinium HumanOmni1-Quad BeadChip.
2010-04-11 | E-GEOD-21168 | biostudies-arrayexpress
Project description:The International Stem Cell Initiative analyzed 127 human embryonic stem cell lines and 11 induced pluripotent cell lines, from 39 laboratories worldwide for genetic changes occurring during culture. Most cell lines were analyzed at an early and late passage. Population structure analysis from SNP detection revealed that the cell lines included representatives of all major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed but haphazardly with no link to time in culture. Structural variants (SVs), below the level of standard chromosome banding, determined from the SNP arrays, also appeared sporadically but no common variants related to culture were observed on chromosomes 1, 12 and 17. However, overlapping SV gains acquired in the chromosome 20q11.21 region during extended culture were identified in over 20% of the cell lines. Three genes within the minimal shared region, ID1, BCL2L1, and HM13, are expressed in human ES cells, with BCL2L1 a strong candidate for driving this culture adaptation of ES cells. In order to provide better insight into the frequency and types of genetic changes affecting human ES cells on prolonged passage, the ISCI has undertaken a survey by karyology and high resolution SNP array of one hundred twenty seven independent human ES cell lines, provided by thirty nine laboratories in twenty countries around the world, particularly to identify the common genetic changes that occur during prolonged culture. Here we append data from the SNP genotyping of the genomic DNA samples extracted from the human embryonic stem cells. A group of eleven human iPS cells from three laboratories was also included to provide a pilot comparison of these pluripotent cells derived by reprogramming.
2011-11-12 | E-GEOD-33522 | biostudies-arrayexpress
Project description:Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyzed the genomes of ten patients with congenital disease that were preselected to carry complex chromosomal rearrangements (CCRs) with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint-junctions indicates that break-repair involves non-homologous or microhomology mediated end-joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred bp and several Mb. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template-switching. Our work provides detailed insight in the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. We analyzed five patient-parent trios with Illumina BeadChip arrays to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients.
2012-05-10 | E-GEOD-37906 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-01-31 | E-GEOD-65454 | biostudies-arrayexpress
Project description:Chromothripsis represents an extreme class of complex chromosome rearrangements (CCRs) with major effects on chromosomal architecture. Although recent studies have associated chromothripsis with congenital abnormalities, the incidence and pathogenic effects of this phenomenon require further investigation. Here, we analyzed the genomes of three families in which chromothripsis rearrangements were transmitted from a female carrier to her child. The chromothripsis in the carriers resulted in completely balanced rearrangements involving 8-23 breakpoint junctions across 3-5 chromosomes. Two carriers did not show any phenotypic malformations, although 3-13 protein coding genes were affected by breakpoints. Unbalanced but stable transmission of a subset of the derivative chromosomes caused apparently de novo complex copy number changes in two children. This resulted in gene dosage changes, which are likely responsible for their severe congenital phenotypes. In contrast, one patient with severe congenital disease, carried all three chromothripsis chromosomes from his healthy mother, but one of the chromosomes acquired de novo rearrangements leading to copy number changes. These results show that the human genome can tolerate extreme reshuffling of chromosomal architecture, including breakage of multiple protein coding genes, without noticeable phenotypic effects. The presence of chromothripsis in healthy carriers strongly affects reproduction and is expected to substantially increase the risk of spontaneous abortions and severe congenital disease. We analyzed one patient-parent-mother's parents quintet (case 1) and a patient-siblings-parent quintet (case 2) with Illumina beadchip arrays and one patient-parent trio (case 3) to test for (de novo) copy number variants and to analyze the parental origin of the complex rearrangements in these patients. For case 2, the mother and patient's SNP array data was previously submitted [GSE37906]. aCGH data for case 3 is submitted seperately.
2015-01-31 | E-GEOD-65452 | biostudies-arrayexpress
Project description:We reveal three-dimensional patterns of tumour growth by exploiting the unique metastasizing patterns of treatment naïve stage IIIC/IV epithelial ovarian cancer. We performed topographic mapping of structural genomic rearrangements, coding mutations, copy number changes and RNA expression in biopsies derived from 27 primary and metastatic sites across three patients. Based on somatic genomic changes, we performed sample clustering and obtained unique insight in natural tumour growth and spread. Based on extensive multi-level profiling, our data highlight the diverse modes of epithelial ovarian cancer development before applying selective pressure from therapy. We performed SNP array analysis on tumor biopsies from 3 patients (P1, P2, P3) with advanced stage ovarian cancer. This submission includes SNP data for 26 tumor biopsies and 5 normal tissue samples.
2013-06-05 | E-GEOD-47633 | biostudies-arrayexpress