Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Diversity of Human Copy Number Variation and Multicopy Genes

ABSTRACT: Copy number variants (CNVs) affect both disease and normal phenotypic variation but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrate accurate estimation of absolute copy number for duplications as small as 1.9 kbp, ranging from 0-48 copies. We identified 4.1 million ‘singly unique nucleotide’ (SUN) positions informative in distinguishing specific copies, and use them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.

ORGANISM(S): Homo sapiens

PROVIDER: GSE24334 | GEO | 2010/09/24

SECONDARY ACCESSION(S): PRJNA132747

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Diversity of Human Copy Number Variation and Multicopy Genes

Project description:Copy number variants (CNVs) affect both disease and normal phenotypic variation but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrate accurate estimation of absolute copy number for duplications as small as 1.9 kbp, ranging from 0-48 copies. We identified 4.1 million ‘singly unique nucleotide’ (SUN) positions informative in distinguishing specific copies, and use them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association. This dataset complements the results from short read sequencing by performing validation on five individuals. We analyzed the 17q21.1 locus in 5 HapMap individuals by array CGH on a custom Agilent 4-plex 310k array performing 1 experiment for each sample. This array was targeted at high density (1 probe/105bp) to 7 genomic loci, including 17q21. The reference individual used was NA19240.

2010-09-24 | E-GEOD-24334 | biostudies-arrayexpress

Whole-genome definitive haplotypes of SNPs and CNVs determined by genotyping duplicated haploid genomes

Project description:Copy number variations (CNVs) constitute the largest portion of the human genome variation. We determined a genome-wide high resolution SNP/CNV haplotype structure of Asians, by analyzing a collection of complete hydatidiform moles (CHMs) of Japanese, using high-density DNA arrays. CHMs are tissues carrying duplicated haploid genomes derived from single sperms, and are suitable material for the detection of CNVs, because they are expected to reveal greater signal to noise ratio in hybridization experiments. Also, the absence of heterozygosity ensures straightforward CNV interpretation without being bothered by overlapping CNV segments. We genotyped 100 CHM genomes using Affymetrix SNP 6.0 and Illumina 1M-duo, created a definitive haplotype map including 1.7 million SNPs and 2339 CNV region (CNVR) that is presented as D-HaploDB Phase 4.1.

2014-02-13 | GSE54948 | GEO

Whole-genome definitive haplotypes of SNPs and CNVs determined by genotyping duplicated haploid genomes

2014-02-13 | E-GEOD-54948 | biostudies-arrayexpress

Mapping of the GDI1 duplication at Xq28 in four unrelated XLMR patients

Project description:In a study to elucidate the genetic defects in patients with X-linked mental retardation (XLMR) we performed X chromosome-specific BAC-array-CGH and identified a 0.33 Mb inherited recurrent copy number gain at Xq28 in affected males of four unrelated XLMR families. All aberrations segregate with the disease in the families and the carrier mothers show a nonrandom X-inactivation. Tiling Xq28 region-specific oligo-array revealed that all aberrations start at the same position (153.218 Mb) and end between 153.530 and 154.542 Mb. The copy number gain is complex in nature but always included 18 genes of which three, RPL10, ATP6AP1 and GDI1, are highly expressed in brain. From these, the copy number of GDI1 correlated with the severity of clinical features since it was duplicated in one family with nonsyndromic moderate MR, triplicated in males from two families with mild MR and additional features, while in a fourth family with a severe syndromic form of MR, it was present in four copies. Moreover, expression analysis revealed copy number-dependent increased mRNA levels in affected patients compared to control individuals. Interestingly, the breakpoint junction regions suggested a yet unknown recombination mechanism between two adjacent but different sets of low copy repeats.

2010-08-17 | GSE17813 | GEO

RNA polymerase I activators count and adjust ribosomal RNA gene copy number

Project description:Ribosome is the most abundant RNA-protein complex in a cell and many copies of the ribosomal RNA gene (rDNA) have to be maintained. However, arrays of tandemly repeated rDNA genes can lose the copies by intra-repeat recombination. Loss of the rDNA copies of Saccharomyces cerevisiae is counteracted by gene amplification whereby the number of rDNA repeats stabilizes around 150 copies, suggesting the presence of a monitoring mechanism that counts and adjusts the number. Here, we report that in response to rDNA copy loss, the upstream activating factor (UAF) for RNA polymerase I which transcribes the rDNA is released and directly bind to a RNA polymerase II transcribed gene, SIR2 to repress, whose gene products silence rDNA recombination. We show that the amount of UAF determines rDNA copies number that is stably maintained. UAF ensures rDNA production not only by rDNA transcription activation but also by its copy number maintenance.

2019-01-03 | GSE116661 | GEO

The Multicopy Gene Sly Represses the Sex Chromosomes in the Male Mouse Germline after Meiosis

Project description:Studies of mice with Y chromosome long arm deficiencies suggest that the male-specific region (MSYq) encodes information required for sperm differentiation and postmeiotic sex chromatin repression (PSCR). Several genes have been identified on MSYq, but because they are present in more than 40 copies each, their functions cannot be investigated using traditional gene targeting. Here, we generate transgenic mice producing small interfering RNAs that specifically target the transcripts of the MSYq-encoded multicopy gene Sly (Sycp3-like Y-linked). Microarray analyses performed on these Sly-deficient males and on MSYq-deficient males show a remarkable up-regulation of sex chromosome genes in spermatids.

2011-05-11 | GSE29198 | GEO

Mapping of the GDI1 duplication at Xq28 in four unrelated XLMR patients

2010-08-16 | E-GEOD-17813 | biostudies-arrayexpress

Refinement and discovery of new hotspots of copy number variation associated with autism spectrum disorder

Project description:Rare DNA copy-number variation (CNV) plays an important role in the underlying genetic etiology of autism and intellectual disability. Although large numbers of copy-number variants (CNVs) have been recently implicated in autism, most are large affecting many genes and specificity of these lesions with respect to classically defined autism as opposed to more broadly defined developmental delay is unclear. We exploited the repeat architecture of the genome to target smaller regions (n=1340 hotspots, median size 15 kbp) flanked by repetitive sequence among 2,240 autism simplex patients and a subset of unaffected parents.

2012-09-30 | GSE39655 | GEO

The Multicopy Gene Sly Represses the Sex Chromosomes in the Male Mouse Germline after Meiosis part 2

2011-05-11 | GSE29200 | GEO

Copy number variation of individual cattle genomes using next-generation sequencing.

Project description:Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome-wide copy number differences among five taurine (three Angus, one Holstein and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1,265 CNV regions comprising ~55.6 Mbp sequence-476 of which (~38%) have not previously been reported. We validated this sequence-based CNV call set with aCGH, qPCR and FISH, achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (~52%, chi squared test; p value <0.05). In contrast, genes related to pathogen- and parasite-resistance, such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNV regions also harbor genes like BPIFA2A (BSP30A) and WC1, suggesting that some CNVs may be associated with breed-specific differences in adaptation, health, and production traits. By providing the first individualized cattle CNV and segmental duplication maps and genome-wide gene copy number estimates, we enable future CNV studies into highly duplicated regions in the cattle genome.

2012-01-25 | GSE31018 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data