Comprehensive characterization of human genome variation by high coverage whole-genome sequencing of forty four Caucasians
Whole genome sequencing studies are essential to obtain a comprehensive understanding of the vast pattern of human genomic variations. Here we report the results of a high-coverage whole genome sequencing study for 44 unrelated healthy Caucasian adults, each sequenced to over 50-fold coverage (avera...
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| Veröffentlicht in: | PloS one 2013-04, Vol.8 (4), p.e59494 |
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| creator | Shen, Hui Li, Jian Zhang, Jigang Xu, Chao Jiang, Yan Wu, Zikai Zhao, Fuping Liao, Li Chen, Jun Lin, Yong Tian, Qing Papasian, Christopher J Deng, Hong-Wen |
| description | Whole genome sequencing studies are essential to obtain a comprehensive understanding of the vast pattern of human genomic variations. Here we report the results of a high-coverage whole genome sequencing study for 44 unrelated healthy Caucasian adults, each sequenced to over 50-fold coverage (averaging 65.8×). We identified approximately 11 million single nucleotide polymorphisms (SNPs), 2.8 million short insertions and deletions, and over 500,000 block substitutions. We showed that, although previous studies, including the 1000 Genomes Project Phase 1 study, have catalogued the vast majority of common SNPs, many of the low-frequency and rare variants remain undiscovered. For instance, approximately 1.4 million SNPs and 1.3 million short indels that we found were novel to both the dbSNP and the 1000 Genomes Project Phase 1 data sets, and the majority of which (∼96%) have a minor allele frequency less than 5%. On average, each individual genome carried ∼3.3 million SNPs and ∼492,000 indels/block substitutions, including approximately 179 variants that were predicted to cause loss of function of the gene products. Moreover, each individual genome carried an average of 44 such loss-of-function variants in a homozygous state, which would completely "knock out" the corresponding genes. Across all the 44 genomes, a total of 182 genes were "knocked-out" in at least one individual genome, among which 46 genes were "knocked out" in over 30% of our samples, suggesting that a number of genes are commonly "knocked-out" in general populations. Gene ontology analysis suggested that these commonly "knocked-out" genes are enriched in biological process related to antigen processing and immune response. Our results contribute towards a comprehensive characterization of human genomic variation, especially for less-common and rare variants, and provide an invaluable resource for future genetic studies of human variation and diseases. |
| doi_str_mv | 10.1371/journal.pone.0059494 |
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Here we report the results of a high-coverage whole genome sequencing study for 44 unrelated healthy Caucasian adults, each sequenced to over 50-fold coverage (averaging 65.8×). We identified approximately 11 million single nucleotide polymorphisms (SNPs), 2.8 million short insertions and deletions, and over 500,000 block substitutions. We showed that, although previous studies, including the 1000 Genomes Project Phase 1 study, have catalogued the vast majority of common SNPs, many of the low-frequency and rare variants remain undiscovered. For instance, approximately 1.4 million SNPs and 1.3 million short indels that we found were novel to both the dbSNP and the 1000 Genomes Project Phase 1 data sets, and the majority of which (∼96%) have a minor allele frequency less than 5%. On average, each individual genome carried ∼3.3 million SNPs and ∼492,000 indels/block substitutions, including approximately 179 variants that were predicted to cause loss of function of the gene products. Moreover, each individual genome carried an average of 44 such loss-of-function variants in a homozygous state, which would completely "knock out" the corresponding genes. Across all the 44 genomes, a total of 182 genes were "knocked-out" in at least one individual genome, among which 46 genes were "knocked out" in over 30% of our samples, suggesting that a number of genes are commonly "knocked-out" in general populations. Gene ontology analysis suggested that these commonly "knocked-out" genes are enriched in biological process related to antigen processing and immune response. Our results contribute towards a comprehensive characterization of human genomic variation, especially for less-common and rare variants, and provide an invaluable resource for future genetic studies of human variation and diseases.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0059494</identifier><identifier>PMID: 23577066</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Adults ; Analysis ; Antigen processing ; Bioinformatics ; Biological activity ; Biological effects ; Biology ; Chromosomes, Human, Y - genetics ; Computer Science ; Consortia ; Deoxyribonucleic acid ; Disease - ethnology ; Disease - genetics ; DNA ; DNA Copy Number Variations - genetics ; DNA sequencing ; DNA, Mitochondrial - genetics ; Female ; Gene frequency ; Gene sequencing ; Genes ; Genetic aspects ; Genetic diversity ; Genetic research ; Genetic testing ; Genome, Human - genetics ; Genomes ; Genomics ; Health care ; Humans ; Immune response ; Immune system ; INDEL Mutation - genetics ; Male ; Medicine ; Mitochondrial DNA ; Mutation Rate ; Polymorphism, Single Nucleotide - genetics ; Public health ; Science ; Sequence Analysis, DNA - methods ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Studies ; White People - genetics</subject><ispartof>PloS one, 2013-04, Vol.8 (4), p.e59494</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Shen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Shen et al 2013 Shen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-6bbb2414ddd3a0e05d63aff65a574fc080231487125f52bd902b578aa705ed8f3</citedby><cites>FETCH-LOGICAL-c692t-6bbb2414ddd3a0e05d63aff65a574fc080231487125f52bd902b578aa705ed8f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618277/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618277/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23577066$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shen, Hui</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><creatorcontrib>Zhang, Jigang</creatorcontrib><creatorcontrib>Xu, Chao</creatorcontrib><creatorcontrib>Jiang, Yan</creatorcontrib><creatorcontrib>Wu, Zikai</creatorcontrib><creatorcontrib>Zhao, Fuping</creatorcontrib><creatorcontrib>Liao, Li</creatorcontrib><creatorcontrib>Chen, Jun</creatorcontrib><creatorcontrib>Lin, Yong</creatorcontrib><creatorcontrib>Tian, Qing</creatorcontrib><creatorcontrib>Papasian, Christopher J</creatorcontrib><creatorcontrib>Deng, Hong-Wen</creatorcontrib><title>Comprehensive characterization of human genome variation by high coverage whole-genome sequencing of forty four Caucasians</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Whole genome sequencing studies are essential to obtain a comprehensive understanding of the vast pattern of human genomic variations. Here we report the results of a high-coverage whole genome sequencing study for 44 unrelated healthy Caucasian adults, each sequenced to over 50-fold coverage (averaging 65.8×). We identified approximately 11 million single nucleotide polymorphisms (SNPs), 2.8 million short insertions and deletions, and over 500,000 block substitutions. We showed that, although previous studies, including the 1000 Genomes Project Phase 1 study, have catalogued the vast majority of common SNPs, many of the low-frequency and rare variants remain undiscovered. For instance, approximately 1.4 million SNPs and 1.3 million short indels that we found were novel to both the dbSNP and the 1000 Genomes Project Phase 1 data sets, and the majority of which (∼96%) have a minor allele frequency less than 5%. On average, each individual genome carried ∼3.3 million SNPs and ∼492,000 indels/block substitutions, including approximately 179 variants that were predicted to cause loss of function of the gene products. Moreover, each individual genome carried an average of 44 such loss-of-function variants in a homozygous state, which would completely "knock out" the corresponding genes. Across all the 44 genomes, a total of 182 genes were "knocked-out" in at least one individual genome, among which 46 genes were "knocked out" in over 30% of our samples, suggesting that a number of genes are commonly "knocked-out" in general populations. Gene ontology analysis suggested that these commonly "knocked-out" genes are enriched in biological process related to antigen processing and immune response. Our results contribute towards a comprehensive characterization of human genomic variation, especially for less-common and rare variants, and provide an invaluable resource for future genetic studies of human variation and diseases.</description><subject>Adult</subject><subject>Adults</subject><subject>Analysis</subject><subject>Antigen processing</subject><subject>Bioinformatics</subject><subject>Biological activity</subject><subject>Biological effects</subject><subject>Biology</subject><subject>Chromosomes, Human, Y - genetics</subject><subject>Computer Science</subject><subject>Consortia</subject><subject>Deoxyribonucleic acid</subject><subject>Disease - ethnology</subject><subject>Disease - genetics</subject><subject>DNA</subject><subject>DNA Copy Number Variations - genetics</subject><subject>DNA sequencing</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Female</subject><subject>Gene frequency</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic research</subject><subject>Genetic testing</subject><subject>Genome, Human - genetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health care</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>INDEL Mutation - genetics</subject><subject>Male</subject><subject>Medicine</subject><subject>Mitochondrial DNA</subject><subject>Mutation Rate</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Public health</subject><subject>Science</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Studies</subject><subject>White People - genetics</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk22L1DAQx4so3nn6DUQLguiLXdOkSdo3wrH4sHBw4NPbME2TNkubrEm7uvfpTd3esSv3QgJJmPzmP5lJJkmeZ2iZEZ6927jRW-iWW2fVEiFa5mX-IDnPSoIXDCPy8Gh_ljwJYRMhUjD2ODnDhHKOGDtPblau33rVKhvMTqWyBQ9yUN7cwGCcTZ1O27EHmzbKul6lO_DmcFLt09Y0bSrdTnloVPqrdZ1azFxQP0dlpbHNJKGdH_ZxHn26glFCMGDD0-SRhi6oZ_N6kXz_-OHb6vPi6vrTenV5tZCsxMOCVVWF8yyv65oAUojWjIDWjALluZaoQJhkecEzTDXFVV0iXFFeAHBEVV1ocpG8POhuOxfEXLYgMkJQiRAvskisD0TtYCO23vTg98KBEX8NzjcC_GBkpwSJcbWkhSwYzStaV8AY4rTERQ4EChq13s_RxqpXtVR28NCdiJ6eWNOKxu2iclZgzqPAm1nAu1jDMIjeBKm6Dqxy43RvzDimBOcRffUPen92M9VATMBY7WJcOYmKy5wXeVZyziK1vIeKo1a9kfGPaRPtJw5vTxwiM6jfQwNjCGL99cv_s9c_TtnXR2yroBva4Lpx-nThFMwPoPQuBK_0XZEzJKYWua2GmFpEzC0S3V4cP9Cd021PkD9O1A16</recordid><startdate>20130405</startdate><enddate>20130405</enddate><creator>Shen, Hui</creator><creator>Li, Jian</creator><creator>Zhang, Jigang</creator><creator>Xu, Chao</creator><creator>Jiang, Yan</creator><creator>Wu, Zikai</creator><creator>Zhao, Fuping</creator><creator>Liao, Li</creator><creator>Chen, Jun</creator><creator>Lin, Yong</creator><creator>Tian, Qing</creator><creator>Papasian, Christopher J</creator><creator>Deng, Hong-Wen</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130405</creationdate><title>Comprehensive characterization of human genome variation by high coverage whole-genome sequencing of forty four Caucasians</title><author>Shen, Hui ; Li, Jian ; Zhang, Jigang ; Xu, Chao ; Jiang, Yan ; Wu, Zikai ; Zhao, Fuping ; Liao, Li ; Chen, Jun ; Lin, Yong ; Tian, Qing ; Papasian, Christopher J ; Deng, Hong-Wen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-6bbb2414ddd3a0e05d63aff65a574fc080231487125f52bd902b578aa705ed8f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Adults</topic><topic>Analysis</topic><topic>Antigen processing</topic><topic>Bioinformatics</topic><topic>Biological activity</topic><topic>Biological effects</topic><topic>Biology</topic><topic>Chromosomes, Human, Y - 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Here we report the results of a high-coverage whole genome sequencing study for 44 unrelated healthy Caucasian adults, each sequenced to over 50-fold coverage (averaging 65.8×). We identified approximately 11 million single nucleotide polymorphisms (SNPs), 2.8 million short insertions and deletions, and over 500,000 block substitutions. We showed that, although previous studies, including the 1000 Genomes Project Phase 1 study, have catalogued the vast majority of common SNPs, many of the low-frequency and rare variants remain undiscovered. For instance, approximately 1.4 million SNPs and 1.3 million short indels that we found were novel to both the dbSNP and the 1000 Genomes Project Phase 1 data sets, and the majority of which (∼96%) have a minor allele frequency less than 5%. On average, each individual genome carried ∼3.3 million SNPs and ∼492,000 indels/block substitutions, including approximately 179 variants that were predicted to cause loss of function of the gene products. Moreover, each individual genome carried an average of 44 such loss-of-function variants in a homozygous state, which would completely "knock out" the corresponding genes. Across all the 44 genomes, a total of 182 genes were "knocked-out" in at least one individual genome, among which 46 genes were "knocked out" in over 30% of our samples, suggesting that a number of genes are commonly "knocked-out" in general populations. Gene ontology analysis suggested that these commonly "knocked-out" genes are enriched in biological process related to antigen processing and immune response. Our results contribute towards a comprehensive characterization of human genomic variation, especially for less-common and rare variants, and provide an invaluable resource for future genetic studies of human variation and diseases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23577066</pmid><doi>10.1371/journal.pone.0059494</doi><tpages>e59494</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2013-04, Vol.8 (4), p.e59494 |
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| language | eng |
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| source | MEDLINE; Public Library of Science; PubMed Central; Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Adult Adults Analysis Antigen processing Bioinformatics Biological activity Biological effects Biology Chromosomes, Human, Y - genetics Computer Science Consortia Deoxyribonucleic acid Disease - ethnology Disease - genetics DNA DNA Copy Number Variations - genetics DNA sequencing DNA, Mitochondrial - genetics Female Gene frequency Gene sequencing Genes Genetic aspects Genetic diversity Genetic research Genetic testing Genome, Human - genetics Genomes Genomics Health care Humans Immune response Immune system INDEL Mutation - genetics Male Medicine Mitochondrial DNA Mutation Rate Polymorphism, Single Nucleotide - genetics Public health Science Sequence Analysis, DNA - methods Single nucleotide polymorphisms Single-nucleotide polymorphism Studies White People - genetics |
| title | Comprehensive characterization of human genome variation by high coverage whole-genome sequencing of forty four Caucasians |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T15%3A15%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Comprehensive%20characterization%20of%20human%20genome%20variation%20by%20high%20coverage%20whole-genome%20sequencing%20of%20forty%20four%20Caucasians&rft.jtitle=PloS%20one&rft.au=Shen,%20Hui&rft.date=2013-04-05&rft.volume=8&rft.issue=4&rft.spage=e59494&rft.pages=e59494-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0059494&rft_dat=%3Cgale_plos_%3EA478419776%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1330900781&rft_id=info:pmid/23577066&rft_galeid=A478419776&rft_doaj_id=oai_doaj_org_article_365afc58c8654b5dba660759284a3a85&rfr_iscdi=true |