We constructed a map of unbalanced svs that is, copy number variants based on whole genome dna sequencing data from 185 human genomes, integrating evidence from complementary sv discovery approaches with extensive experimental validations. Maps of human genome copy number variation cnv are maturing into useful resources for complex disease genetics. Supplementary information for a copy number variation map of. Pdf a copy number variation map of the human genome. Copy number variation is a type of structural variation. We constructed genomewide copy number maps across 159 genomes at 3kbp resolution fig. Highresolution microarray technology is routinely used in basic research and clinical practice to efficiently detect copy number variants cnvs across the entire human genome. Certainly, the 5% of the genome already known to display cnv is considerably larger than the 0. Oct 29, 2010 we constructed genome wide copy number maps across 159 genomes at 3kbp resolution fig.
While previous work has uncovered some structural variation in the human genome, a sequencebased map provides much finer detail. The haplotype map, or hapmap, is a tool that allows researchers to find genes and genetic variations that affect health and disease. Genetic variation ranges in size from the fine scale of snps to the multikilobase deletions and duplications that comprise copy number varia. Apr 24, 2017 highresolution microarray technology is routinely used in basic research and clinical practice to efficiently detect copy number variants cnvs across the entire human genome. Copy number variation is surprisingly common among humans and can be involved in phenotypic diversity and variable susceptibility to complex diseases, but little is known of the extent of copy number variation in nonhuman primates. Germline cnvs are inherited genetic events that could confer susceptibility to various types of cancer 1 3 as well as other diseases 4, 5. A nationwide team of researchers, funded in part by nihs national human genome research institute nhgri, constructed the new map by analyzing the genomes of 8 people. Global variation in copy number in the human genome.
To facilitate analysis of copy number variations, single nucleotide polymorphisms and loss of heterozygosity events in these pathogens, we developed a pipeline for analyzing diverse genomescale datasets from microarray, deep sequencing, and. Array comparative genomic hybridization has been used widely to identify cnvs genome wide, but the nextgeneration sequencing technology provides an opportunity to characterize cnvs genome wide with. Oligonucleotide array platforms originally developed for snp genotyping have been successfully used for segmental aneuploidy profiling 4, 5, 7. A collection of 14 barley genotypes including eight cultivars and six wild barleys were used. An integrated approach including characterization of single nucleotide variants and cnvs in a large number of individuals with disease and normal genomes holds the promise. The development and validation of novel approaches to accurately and quickly map copy number changes in the human genome is important for the implementation of novel diagnostic strategies. Dna copy number variation cnv is a major class of genome variations in the human genome. Scherer1,2 2mclaughlin centre and department of molecular genetics, university of toronto, toronto, on, canada m5g 1l7 2department of molecular genetics and mclaughlin centre, university of toronto, toronto. Copy number variation in the human genome and its implication in autoimmunity.
Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy. Copy number variation and human genome maps request pdf. Copy number variation cnv of dna sequences is functionally. Our map encompassed 22,025 deletions and 6,000 additional svs, including. Oct 22, 2015 the populations of the arabian peninsula remain the least represented in public genetic databases, both in terms of single nucleotide variants and of larger genomic mutations. A copy number variation cnv is when the number of copies of a particular gene varies from one individual to the next. We constructed a map of unbalanced svs that is, copy number variants based on whole genome dna sequencing data from 185 human genomes, integrating evidence. Until recently, genomewide interrogation of cnv was not easily applicable to populationbased studies. To date, attempts to identify these genes have not really considered the role cnvs may play in human health. Dna copy number variations cnvs play an important role in the pathogenesis and progression of cancer and confer susceptibility to a variety of human disorders.
Here we use array comparative genomic hybridization to explore the extent of this type of structural variation in domesticated barley cultivars and wild barleys. Mapping copy number variation by populationscale genome. In recent decades, copy number variation cnv has been recognized as the common type of polymorphism in the genomes of humans, animals and plants 3 4. Copy number variation in the human genome and its implications for cardiovascular disease. A large data resource of genomic copy number variation across. Genomic copy number variations cnvs are structural variations that involve deletions andor. Mutational and selective effects on copynumber variants in the human genome.
Following the completion of the human genome project, it became apparent that the genome experiences gains and losses of genetic material. However, the landscape of copy number variation still remains largely unexplored, especially for smaller cnvs and those embedded within complex regions of the human genome. Supplementary information for a copy number variation map. Copy number analysis of wholegenome data using bicseq2 and. Clinical interpretation of copy number variants in the human genome. Finescale structural variation of the human genome. Comprehensive performance comparison of highresolution array. Pmid 17122084 genomewide detection of human copy number variations using highdensity dna oligonucleotide arrays. Here, we performed a genome wide analysis and identified large indels 50499 bp and cnvs 500 bp and larger present in these accessions. The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Pdf poster determination of genomic copy number variation cnv using the snplex genotyping system cant direct link snp and cnv variation correlated with altered activity in almost 900 and 240 genes, respectively. A major contribution to the genome variability among individuals comes from deletions and duplications collectively termed copy number variations cnvs. Mar 01, 2015 a copy number variation map of the human genome. These svs1 affect the coding regions of 1676 genes, some of which are associated with cucumber domestication.
A copy number variation map of the human genome nature. Nov 15, 2011 dna copy number variations cnvs play an important role in the pathogenesis and progression of cancer and confer susceptibility to a variety of human disorders. Copy number variation and human genome maps steven a mccarroll maps of human genome copy number variation cnv are maturing into useful resources for complex disease genetics. We constructed genome wide copy number maps across 159 genomes at 3kbp resolution fig. The populations of the arabian peninsula remain the least represented in public genetic databases, both in terms of single nucleotide variants and of larger genomic mutations. The elucidation of the entire human genome has made possible our current effort to develop a haplotype map of the human genome. Copy number variation an overview sciencedirect topics. In just a few short years, the research community has identified. Scherer1,2 2mclaughlin centre and department of molecular genetics, university of toronto, toronto, on. We identified 952 large cnvs greater than 50 kbp across 159 individuals 9.
List of cnv copy number variation regions in the human genome. These data are compared to existing comparative genomic hybridization data using an array technology. Can a change in the number of genes affect health and. The human genome is comprised of 6 billion chemical bases or nucleotides of dna packaged into two sets of 23 chromosomes, one set inherited from each parent. Diversity of human copy number variation and multicopy. With cnvs added to snps, the human genome has ceased to exist as a defined entity and is instead becoming a fluid continuum. A copy number variation map of the human genome request pdf. Copy number variations in the genome of the qatari population. There is growing evidence for the prevalence of copy number variation cnv and its role in phenotypic variation in many eukaryotic species.
A definition of copy number variation is included in the talking genome glossary from the national human genome research institute. We constructed a map of unbalanced svs that is, copy number variants based on whole genome dna sequencing data from 185 human genomes, integrating evidence from complementary sv discovery. We have used two arraybased comparative genomic hybridization platforms to identify a total of 355 copy number variants cnvs in the genomes of 20. For people interested in more technical data, several institutions provide databases of structural differences in human dna, including copy number variation. Copy number variation detection in wholegenome sequencing. The extent to which copy number variation contributes to human disease is not yet known. Copy number variation and human genome maps mccarroll lab. Four new studies increase the resolution of cnv maps and seek to locate human phenotypic variation on these maps.
One of us rr presented preliminary results from the construction of a new highresolution cnv map by the genome structural variation gsv consortium. A copy number variation morbidity map of developmental delay. Proof of extensive copy number variation in the human genome. Hotspots for copy number variation in chimpanzees and humans. Genomewide mapping of structural variations reveals a copy. A comprehensive analysis of common copynumber variations in. Highresolution mapping and analysis of copy number variations in the human genome.
It was generally thought that genes were almost always present in two copies in a genome. Second, the cnv map is being used to study familial. We have constructed a firstgeneration cnv map of the human genome through the study of 270. The copy number variation cnv map of the human genome documents the extent and characteristics of cnv among healthy populations. The two primary applications of these tools, genomewide association studies gwas and copy number variation cnv identification, have enabled researchers to achieve a greater understanding of how genetics contributes to human health and disease progression. Nov 20, 2014 the design of effective antimicrobial therapies for serious eukaryotic pathogens requires a clear understanding of their highly variable genomes. Recent analyses of sequencing data for accessions of arabidopsis thaliana were focused on small variations and did not include cnvs. In recent decades, copy number variation cnv has been recognized as the common type of polymorphism in the genomes of humans, animals and plants 34. Global variation in copy number in the human genome europe pmc. The centre for applied genomics database of genomic variants. We have used two arraybased comparative genomic hybridization platforms to identify a total of 355 copy number variants cnvs in the genomes of 20 wildborn. We systematically compared the genome wide cnv detection power of. Jul 23, 2004 the extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Jan 23, 2009 until recently, genome wide interrogation of cnv was not easily applicable to populationbased studies.
Although most neurons in normal brains are euploid, large subchromosomal cnvs were commonly identified, suggesting genetic heterogeneity within normal human brains. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number. Our map encompassed 22,025 deletions and 6,000 additional svs, including insertions and tandem duplications. Copy number variation goes clinical genome biology full text. Whole genome survey of copy number variation in the. Diversity of human copy number variation and multicopy genes. A new generation of arrays combining high probe densities with optimized designs will comprise essential tools for genome analysis in the coming years. May 23, 2006 copy number variation is surprisingly common among humans and can be involved in phenotypic diversity and variable susceptibility to complex diseases, but little is known of the extent of copy number variation in nonhuman primates. Map of structural variation in the human genome national. Copy number variation cnv in the human genome significantly influences human diversity and predisposition to disease sebat et al 2004, sharp et al. Copy number variation as well as single base differences, studies using the human genome sequence revealed a new type of genetic variation, in which large regions of dna are absent from or duplicated in different individuals.
Dna copy number variation has long been associated with specific chromosomal rearrangements and genomic. Copynumber variants have already been associated with some diseases and disease susceptibilities and are likely to prove as significant as sequence polymorphisms in this respect. Here, we show that largescale copy number polymorphisms cnps about 100 kilobases and greater contribute substantially to genomic variation between normal humans. Copy number variations cnvs greatly contribute to intraspecies genetic polymorphism and phenotypic diversity. Human copy number variation and complex genetic disease. Four new studies increase the resolution of cnv maps and seek to locate human. A copy number variation in human ncf1 and its pseudogenes. During just the past two years, five studies have addressed the phenomenon of copy number variation in the horse genome 35,36,37,38,39 contributing to our knowledge about the genomic landscape. A data resource for clinical and research applications. Array comparative genomic hybridization has been used widely to identify cnvs genome wide, but the nextgeneration sequencing technology provides an opportunity to characterize cnvs genome wide with unprecedented resolution. Copy number variation cnv is a phenomenon in which sections of the genome are repeated and the number of repeats in the genome varies between individuals. Clonal somatic cnvs were identified from both normal and diseased human brains. Copynumber variation cnv the presence of additional or missing segments of chromosomes in some individuals has been found to be abundant in humans and adds another dimension of variation to the genome. To facilitate analysis of copy number variations, single nucleotide polymorphisms and loss of heterozygosity events in these pathogens, we developed a pipeline for analyzing diverse genome scale datasets from microarray, deep sequencing, and.
Largescale copy number polymorphism in the human genome. A copy number variation map of the human genome semantic. Based on the map, we discovered a copy number variation cnv2 involving four genes that defines the female f locus and gives rise to gynoecious cucumber plants, which bear only female flowers and set fruit at almost every node. Less than 2% of the human genome codes for protein the human genome encodes for approx.
Pdf a copy number variation map of the human genome scinapse. Evan eichler and colleagues analyze copy number variation in 15,767 children with intellectual disability, developmental delay, congenital birth defects andor other related phenotypes. Ultimately, the sheer magnitude of cnv discovery the essence of which we captured in the title global variation in copy number in the human genome is what has made this paper a citation classic. Here, we performed a genomewide analysis and identified large indels 50499 bp and cnvs 500 bp and larger present in these accessions. Mapping copy number variation by population scale genome. Depending on the level of stringency of the map, 4. The design of effective antimicrobial therapies for serious eukaryotic pathogens requires a clear understanding of their highly variable genomes. We present the first highresolution copy number variation cnv map for a gulf arab population, using a hybrid approach that integrates array genotyping intensity data and nextgeneration sequencing reads to call cnvs. Highresolution mapping and analysis of copy number.
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