Linkage Disequilibrium at the Angelman Syndrome Gene UBE3A in Autism Families

Autistic disorder is a neurodevelopmental disorder with a complex genetic etiology. Observations of maternal duplications affecting chromosome 15q11–q13 in patients with autism and evidence for linkage and linkage disequilibrium to markers in this region in chromosomally normal autism families indicate the existence of a susceptibility locus. We have screened the families of the Collaborative Linkage Study of Autism for several markers spanning a candidate region covering ∼2 Mb and including the Angelman syndrome gene (UBE3A) and a cluster of γ-aminobutyric acid (GABAA) receptor subunit genes (GABRB3, GABRA5, and GABRG3). We found significant evidence for linkage disequilibrium at marker D15S122, located at the 5′ end of UBE3A. This is the first report, to our knowledge, of linkage disequilibrium at UBE3A in autism families. Characterization of null alleles detected at D15S822 in the course of genetic studies of this region showed a small (∼5-kb) genomic deletion, which was present at somewhat higher frequencies in autism families than in controls.