RESEARCH Identification of rare X-link u r

Full list of author information is available at the end of the articleBackground The rapid development of better methods of targeted enrichment and genome sequencing has made it possible to detect a more complete spectrum of genetic variation [1-3]. These approaches hold out the hope of uncovering the genetic basis of polygenic complex human diseases, including autism (OMIM 209850), a childhood-onset disorder characterized by impaired social interactions, abnormal verbal communication, restricted interests, and repetitive behaviors. Autism has an estimated preva-lence of one percent [4,5], and one of its most striking epidemiological features is a four-fold excess of affected male individuals. Autism, or the broader autism spectrum disorder (ASD) phenotype, is an example of a highly heterogenous, multi-factorial disorder with substantial heritability [6-13], (see reviews in [14,15]). Recent reports, in which X-chromosome coding exons in individuals with ASD were sequenced, iden