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Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity. In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novo mutations, inherited variants,...
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| Published in: | Journal of genetics and genomics 2018-10, Vol.45 (10), p.527-538 |
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| creator | Wu, Jinyu Yu, Ping Jin, Xin Xu, Xiu Li, Jinchen Li, Zhongshan Wang, Mingbang Wang, Tao Wu, Xueli Jiang, Yi Cai, Wanshi Mei, Junpu Min, Qingjie Xu, Qiong Zhou, Bingrui Guo, Hui Wang, Ping Zhou, Wenhao Hu, Zhengmao Li, Yingrui Cai, Tao Wang, Yi Xia, Kun Jiang, Yong-Hui Sun, Zhong Sheng |
| description | Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity. In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novo mutations, inherited variants, copy number variants (CNVs) and genomic structural variants. A higher mutation rate (Poisson test, P |
| doi_str_mv | 10.1016/j.jgg.2018.09.002 |
| format | article |
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In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novo mutations, inherited variants, copy number variants (CNVs) and genomic structural variants. A higher mutation rate (Poisson test, P < 2.2 × 10−16) in exonic (1.37 × 10−8) and 3′-UTR regions (1.42 × 10−8) was revealed in comparison with that of whole genome (1.05 × 10−8). Using an integrated model, we identified 87 potentially risk genes (P < 0.01) from 4832 genes harboring various rare deleterious variants, including CHD8 and NRXN2, implying that the disorders may be in favor to multiple-hit. In particular, frequent rare inherited mutations of several microcephaly-associated genes (ASPM, WDR62, and ZNF335) were found in ASD. In chromosomal structure analyses, we found four de novo CNVs and one de novo chromosomal rearrangement event, including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1, which causes Angelman syndrome and microcephaly, and a disrupted TNR due to de novo chromosomal translocation t(1; 5)(q25.1; q33.2). Taken together, our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD. Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders, such as ASD, could provide novel insights into pathogenesis, diagnosis and treatment.</description><identifier>ISSN: 1673-8527</identifier><identifier>DOI: 10.1016/j.jgg.2018.09.002</identifier><identifier>PMID: 30392784</identifier><language>eng</language><publisher>China: Elsevier Ltd</publisher><subject>Autism spectrum disorders ; De novo mutations ; Microcephaly-associated genes ; Whole-genome sequencing</subject><ispartof>Journal of genetics and genomics, 2018-10, Vol.45 (10), p.527-538</ispartof><rights>2018</rights><rights>Copyright © 2018. Published by Elsevier Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-c29fa455722af8af2da2980daa763cfad40ddc234e798fb49a8824af23a08e793</citedby><cites>FETCH-LOGICAL-c353t-c29fa455722af8af2da2980daa763cfad40ddc234e798fb49a8824af23a08e793</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27900,27901</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30392784$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Jinyu</creatorcontrib><creatorcontrib>Yu, Ping</creatorcontrib><creatorcontrib>Jin, Xin</creatorcontrib><creatorcontrib>Xu, Xiu</creatorcontrib><creatorcontrib>Li, Jinchen</creatorcontrib><creatorcontrib>Li, Zhongshan</creatorcontrib><creatorcontrib>Wang, Mingbang</creatorcontrib><creatorcontrib>Wang, Tao</creatorcontrib><creatorcontrib>Wu, Xueli</creatorcontrib><creatorcontrib>Jiang, Yi</creatorcontrib><creatorcontrib>Cai, Wanshi</creatorcontrib><creatorcontrib>Mei, Junpu</creatorcontrib><creatorcontrib>Min, Qingjie</creatorcontrib><creatorcontrib>Xu, Qiong</creatorcontrib><creatorcontrib>Zhou, Bingrui</creatorcontrib><creatorcontrib>Guo, Hui</creatorcontrib><creatorcontrib>Wang, Ping</creatorcontrib><creatorcontrib>Zhou, Wenhao</creatorcontrib><creatorcontrib>Hu, Zhengmao</creatorcontrib><creatorcontrib>Li, Yingrui</creatorcontrib><creatorcontrib>Cai, Tao</creatorcontrib><creatorcontrib>Wang, Yi</creatorcontrib><creatorcontrib>Xia, Kun</creatorcontrib><creatorcontrib>Jiang, Yong-Hui</creatorcontrib><creatorcontrib>Sun, Zhong Sheng</creatorcontrib><title>Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing</title><title>Journal of genetics and genomics</title><addtitle>J Genet Genomics</addtitle><description>Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity. In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novo mutations, inherited variants, copy number variants (CNVs) and genomic structural variants. A higher mutation rate (Poisson test, P < 2.2 × 10−16) in exonic (1.37 × 10−8) and 3′-UTR regions (1.42 × 10−8) was revealed in comparison with that of whole genome (1.05 × 10−8). Using an integrated model, we identified 87 potentially risk genes (P < 0.01) from 4832 genes harboring various rare deleterious variants, including CHD8 and NRXN2, implying that the disorders may be in favor to multiple-hit. In particular, frequent rare inherited mutations of several microcephaly-associated genes (ASPM, WDR62, and ZNF335) were found in ASD. In chromosomal structure analyses, we found four de novo CNVs and one de novo chromosomal rearrangement event, including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1, which causes Angelman syndrome and microcephaly, and a disrupted TNR due to de novo chromosomal translocation t(1; 5)(q25.1; q33.2). Taken together, our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD. Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders, such as ASD, could provide novel insights into pathogenesis, diagnosis and treatment.</description><subject>Autism spectrum disorders</subject><subject>De novo mutations</subject><subject>Microcephaly-associated genes</subject><subject>Whole-genome sequencing</subject><issn>1673-8527</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kLtOwzAUhj2AaLk8AAvKyJLgSy62mFAFBakSC8yWa5-kjpI42E1R3x5XLYxMlu3v_4_Oh9AtwRnBpHxos7ZpMooJz7DIMKZnaE7KiqW8oNUMXYbQYlxwQYoLNGOYCVrxfI7MEgbXW510ajBBqxFC4upksbEDBEjC6Lwy8VtNWxv6eAe99VOfGBucN-BD4mEHqgOTrPfJ98Z1kDaHypiFrwkGbYfmGp3Xqgtwczqv0OfL88fiNV29L98WT6tUs4JtU01FrfKiqChVNVc1NYoKjo1SVcl0rUyOjdGU5VAJXq9zoTineeSYwjy-sSt0f-wdvYuzw1b2Nmjo4m7gpiApYdEBK0ocUXJEtXcheKjl6G2v_F4SLA9CZSujUHkQKrGQUWjM3J3qp3UP5i_xazMCj0cA4pI7C14GbaMCMNZHb9I4-0_9DyQsilM</recordid><startdate>20181020</startdate><enddate>20181020</enddate><creator>Wu, Jinyu</creator><creator>Yu, Ping</creator><creator>Jin, Xin</creator><creator>Xu, Xiu</creator><creator>Li, Jinchen</creator><creator>Li, Zhongshan</creator><creator>Wang, Mingbang</creator><creator>Wang, Tao</creator><creator>Wu, Xueli</creator><creator>Jiang, Yi</creator><creator>Cai, Wanshi</creator><creator>Mei, Junpu</creator><creator>Min, Qingjie</creator><creator>Xu, Qiong</creator><creator>Zhou, Bingrui</creator><creator>Guo, Hui</creator><creator>Wang, Ping</creator><creator>Zhou, Wenhao</creator><creator>Hu, Zhengmao</creator><creator>Li, Yingrui</creator><creator>Cai, Tao</creator><creator>Wang, Yi</creator><creator>Xia, Kun</creator><creator>Jiang, Yong-Hui</creator><creator>Sun, Zhong Sheng</creator><general>Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20181020</creationdate><title>Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing</title><author>Wu, Jinyu ; 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In this study, we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD, including de novo mutations, inherited variants, copy number variants (CNVs) and genomic structural variants. A higher mutation rate (Poisson test, P < 2.2 × 10−16) in exonic (1.37 × 10−8) and 3′-UTR regions (1.42 × 10−8) was revealed in comparison with that of whole genome (1.05 × 10−8). Using an integrated model, we identified 87 potentially risk genes (P < 0.01) from 4832 genes harboring various rare deleterious variants, including CHD8 and NRXN2, implying that the disorders may be in favor to multiple-hit. In particular, frequent rare inherited mutations of several microcephaly-associated genes (ASPM, WDR62, and ZNF335) were found in ASD. In chromosomal structure analyses, we found four de novo CNVs and one de novo chromosomal rearrangement event, including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1, which causes Angelman syndrome and microcephaly, and a disrupted TNR due to de novo chromosomal translocation t(1; 5)(q25.1; q33.2). Taken together, our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD. Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders, such as ASD, could provide novel insights into pathogenesis, diagnosis and treatment.</abstract><cop>China</cop><pub>Elsevier Ltd</pub><pmid>30392784</pmid><doi>10.1016/j.jgg.2018.09.002</doi><tpages>12</tpages></addata></record> |
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| subjects | Autism spectrum disorders De novo mutations Microcephaly-associated genes Whole-genome sequencing |
| title | Genomic landscapes of Chinese sporadic autism spectrum disorders revealed by whole-genome sequencing |
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