Analysis of the effects of rare variants on splicing identifies alterations in GABAA receptor genes in autism spectrum disorder individuals.

ABSTRACT: A large-scale sequencing screen of X-linked synaptic genes in individuals with autism spectrum disorder (ASD) or schizophrenia (SCZ), two common neurodevelopmental disorders, identified many variants most of which have no easily predictable effect on gene function. In this report, we evaluated the impact of these rare missense and silent variants on gene splicing. For this purpose, we used complementary in silico analyses, in vitro minigene-based assays and RNA prepared from lymphoblastoid cells derived from patients with these mutations. Our goal was to identify the variants which might either create or disrupt an acceptor splice site, a donor splice site or an exonic splicing enhancer, thus leading to aberrant splicing that could be involved in the pathogenesis of ASD or SCZ. We identifi

SUBMITTER: Piton A 

PROVIDER: S-EPMC3722945 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature