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Paternally inherited cis-regulatory structural variants are associated with autism.
Brandler, William M; Antaki, Danny; Gujral, Madhusudan; Kleiber, Morgan L; Whitney, Joe; Maile, Michelle S; Hong, Oanh; Chapman, Timothy R; Tan, Shirley; Tandon, Prateek; Pang, Timothy; Tang, Shih C; Vaux, Keith K; Yang, Yan; Harrington, Eoghan; Juul, Sissel; Turner, Daniel J; Thiruvahindrapuram, Bhooma; Kaur, Gaganjot; Wang, Zhuozhi; Kingsmore, Stephen F; Gleeson, Joseph G; Bisson, Denis; Kakaradov, Boyko; Telenti, Amalio; Venter, J Craig; Corominas, Roser; Toma, Claudio; Cormand, Bru; Rueda, Isabel; Guijarro, Silvina; Messer, Karen S; Nievergelt, Caroline M; Arranz, Maria J; Courchesne, Eric; Pierce, Karen; Muotri, Alysson R; Iakoucheva, Lilia M; Hervas, Amaia; Scherer, Stephen W; Corsello, Christina; Sebat, Jonathan.
Afiliação
  • Brandler WM; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Antaki D; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Gujral M; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Kleiber ML; Human Longevity, Inc., San Diego, CA 92121, USA.
  • Whitney J; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Maile MS; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Hong O; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Chapman TR; Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA.
  • Tan S; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Tandon P; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Pang T; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Tang SC; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Vaux KK; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Yang Y; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Harrington E; The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
  • Juul S; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Turner DJ; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Thiruvahindrapuram B; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Kaur G; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Wang Z; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Kingsmore SF; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Gleeson JG; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Bisson D; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Kakaradov B; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Telenti A; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Venter JC; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Corominas R; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Toma C; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Cormand B; Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
  • Rueda I; Department of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Guijarro S; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Messer KS; Rady Children's Hospital, San Diego, CA 92123, USA.
  • Nievergelt CM; Beyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
  • Arranz MJ; Rady Children's Hospital, San Diego, CA 92123, USA.
  • Courchesne E; Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • Pierce K; Oxford Nanopore Technologies, Inc., NY 10013, USA.
  • Muotri AR; Oxford Nanopore Technologies, Inc., NY 10013, USA.
  • Iakoucheva LM; Oxford Nanopore Technologies, Inc., NY 10013, USA.
  • Hervas A; Oxford Nanopore Technologies Ltd., Oxford, UK.
  • Scherer SW; The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
  • Corsello C; The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
  • Sebat J; The Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
Science ; 360(6386): 327-331, 2018 04 20.
Article em En | MEDLINE | ID: mdl-29674594
ABSTRACT
The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Variação Genética / Regiões Promotoras Genéticas / Predisposição Genética para Doença / Transtorno do Espectro Autista / Herança Paterna Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Variação Genética / Regiões Promotoras Genéticas / Predisposição Genética para Doença / Transtorno do Espectro Autista / Herança Paterna Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article