A comprehensive analysis of copy number variations in the human genome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE5442 | GEO | 2006/12/06
SECONDARY ACCESSION(S): PRJNA96111
REPOSITORIES: GEO
Similar Datasets
Project description:Copy number variations (CNVs), which represent a significant source of genetic diversity in mammals, are currently being associated with phenotypes of clinical relevance, mostly in humans and mice. Notwithstanding, little is known about the extent of CNV that contributes to genetic variation in cattle. This study reports the highest resolution map of copy number variation in the cattle genome, with 304 CNV regions (CNVRs) being identified among the genomes of 20 bovine samples from 4 dairy and beef breeds. We used a set of NimbleGen CGH arrays that tile across the assayable portion of the cattle genome with approximately 6.3 million probes, at a 301 bp median probe spacing. These CNVRs covered 0.68% (23 Mb) of the genome, and ranged in size from 1.7 to 2,031 kb (median size 16.7 kb). About 20% of the CNVs colocalized with segmental duplications while 30% encompassed genes, mostly related with environmental response. About 10% of the orthologous CNV cow-human genes are related with human disease susceptibility and, hence, may have important phenotypic consequences. Together, this analysis provides a useful resource to assist with the assessment of CNVs in the contexts of bovine variation, health and productive efficiency.
2010-04-22 | GSE18174 | GEO
Project description:Copy number variations (CNVs), which represent a significant source of genetic diversity in mammals, are currently being associated with phenotypes of clinical relevance, mostly in humans and mice. Notwithstanding, little is known about the extent of CNV that contributes to genetic variation in cattle. This study reports the highest resolution map of copy number variation in the cattle genome, with 304 CNV regions (CNVRs) being identified among the genomes of 20 bovine samples from 4 dairy and beef breeds. We used a set of NimbleGen CGH arrays that tile across the assayable portion of the cattle genome with approximately 6.3 million probes, at a 301 bp median probe spacing. These CNVRs covered 0.68% (23 Mb) of the genome, and ranged in size from 1.7 to 2,031 kb (median size 16.7 kb). About 20% of the CNVs colocalized with segmental duplications while 30% encompassed genes, mostly related with environmental response. About 10% of the orthologous CNV cow-human genes are related with human disease susceptibility and, hence, may have important phenotypic consequences. Together, this analysis provides a useful resource to assist with the assessment of CNVs in the contexts of bovine variation, health and productive efficiency. 20 samples were analyzed in a dye-swap loop design. In order to cover the latest bovine genome assembly (bt4) with high density, custom Nimblegen HD2 CGH arrays were planned in 3 designs. Each design covered a specific set of chromosomes with 2.1M probes, which yielded 420 bp of average probe spacing (301 bp median probe spacing).
2010-04-22 | E-GEOD-18174 | biostudies-arrayexpress
Project description:To identify susceptibility genes concerning copy number variations (CNVs) in rheumatoid arthritis (RA), a case-control genome-wide CNV analyses was carried out by Roche Nimblegen array-based CGH. In this study, 15 RA patients and 1 control (Non-RA) were included.
2010-06-09 | GSE22108 | GEO
Project description:The contribution to genetic diversity of genomic segmental copy number variations (CNVs) is less well understood than that of single-nucleotide polymorphisms (SNPs). While less frequent than SNPs, CNVs have greater potential to affect phenotype. In this study, we have performed the most comprehensive survey to date of CNVs in mice, analyzing the genomes of 42 Mouse Phenome Consortium priority strains. This microarray comparative genomic hybridization (CGH)-based analysis has identified 2094 putative CNVs, with an average of 10 Mb of DNA in 51 CNVs when individual mouse strains were compared to the reference strain C57BL/6J. This amount of variation results in gene content that can differ by hundreds of genes between strains. These genes include members of large families such as the major histocompatibility and pheromone receptor genes, but there are also many singleton genes including genes with expected phenotypic consequences from their deletion or amplification. Using a whole-genome association analysis, we demonstrate that complex multigenic phenotypes, such as food intake, can be associated with specific copy number changes. Keywords: comparative genomic hybridization
2007-11-06 | GSE9186 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE28239: Identification and functional impact of genomic copy number variants in zebrafish, an important human disease model (Zebrafish Strain CNVs) (expression array) GSE28276: Identification and functional impact of genomic copy number variants in zebrafish, an important human disease model (Zebrafish Strain CNVs) (CGH ZV81M) GSE28278: Identification and functional impact of genomic copy number variants in zebrafish, an important human disease model (Zebrafish Strain CNVs) (CGH ZV81M 2) GSE33962: Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis (CGH) Refer to individual Series
2011-12-27 | E-GEOD-28328 | 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: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:Comparative genomic hybridization (CGH) analysis of CiPSCs (clone CiPS-57 and CiPS-58) and OSKM-iPSCs. C57BL/6 mouse embryonic fibroblasts (MEFs) genome DNA as a reference. No consistent copy number variations (CNVs) among CiPSCs and OSKM-iPSCs.
2013-07-22 | GSE48231 | GEO
Project description:Background: Multiple sclerosis (MS) is a complex disorder thought to result from an interaction between environmental and genetic predisposing factors which have not yet been characterised, although it is known to be associated with the HLA region on 6p21.32. Recently, a picture of chronic cerebrospinal venous insufficiency (CCSVI), consequent to stenosing venous malformation of the main extra-cranial outflow routes (VM), has been described in patients affected with MS, introducing an additional phenotype with possible pathogenic significance. Methods: In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate. Results: In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r=0.6590, p=0.0104; linear regression analysis r=0.6577, p=0.0106). The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype. Conclusions: The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease. 8 female and 7 male MS patients
2010-03-03 | E-GEOD-20334 | biostudies-arrayexpress
Project description:The study was carried out to identify copy number variations using array-CGH in family having three children affected with albinism (OCA1B) and the males were affected with ID. Agilent’s SureScan microarray scanner with SurePrint G3 Human CGH, 8x60K array platform was used for the study. The probes used for the experiment was approximately 60000 oligonucleotide, allowing detection of deletions above 200 Kb and duplication above 500 kb in entire human genome. CytoGenomics software used to carryout data analysis revealed CNVs in participants.
2021-12-03 | GSE190026 | GEO