| Literature DB >> 29674594 |
William M Brandler1,2,3,4, Danny Antaki1,2,3,5, Madhusudan Gujral1,2,3, Morgan L Kleiber1,2,3, Joe Whitney6, Michelle S Maile1,2,3, Oanh Hong1,2,3, Timothy R Chapman1,2,3, Shirley Tan1,2,3, Prateek Tandon1,2,3, Timothy Pang1,7, Shih C Tang1,7, Keith K Vaux8, Yan Yang9, Eoghan Harrington9, Sissel Juul9, Daniel J Turner10, Bhooma Thiruvahindrapuram6, Gaganjot Kaur6, Zhuozhi Wang6, Stephen F Kingsmore11, Joseph G Gleeson12, Denis Bisson4, Boyko Kakaradov4, Amalio Telenti4, J Craig Venter4,13, Roser Corominas14,15, Claudio Toma16,17,18, Bru Cormand15,16,19,20, Isabel Rueda21, Silvina Guijarro22, Karen S Messer23, Caroline M Nievergelt2, Maria J Arranz24, Eric Courchesne25, Karen Pierce25, Alysson R Muotri3, Lilia M Iakoucheva2, Amaia Hervas22, Stephen W Scherer6,26,27, Christina Corsello2,7, Jonathan Sebat28,2,3.
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.Entities:
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Year: 2018 PMID： 29674594 PMCID： PMC6449150 DOI： 10.1126/science.aan2261
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728