Paternally inherited cis-regulatory structural variants are associated with autism.
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
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Regiões Promotoras Genéticas
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Predisposição Genética para Doença
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Transtorno do Espectro Autista
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Herança Paterna
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article