Putative identification of susceptibility genes for autism on 15q11-q13: Role of UBE3A and ATP10A

The etiology of autism is still largely unknown despite our current understanding from family and twin studies that genetics plays a substantial role in the etiology of the disorder. Moreover, integrating data from linkage studies and analyses of chromosomal abnormalities allow identifying 15q11-q13 as one of the regions of particular etiopathogenetic interest for autism and autism related disorders. In an effort to find the autism susceptibility genes potentially harbored in this chromosomal region we have screened a set of markers spanning two known imprinted, maternally expressed genes, UBE3A and ATP10A, selected because they are both positional and candidate genes. We replicated evidence of Linkage Disequilibrium at marker D15S122, located at the 5’ end of UBE3A and originally reported by Nurmi (2001). In addition, our analyses show also one significant haplotype that includes D15S122 at UBE3A and D15S1535 and SNP3 at ATP10A. These findings are of particular interest considering that the association of D15S122 has never been replicated until now and that UBE3A is the gene responsible for the Angelmann Syndrome, that shares neurological and behavioral abnormalities with the autism spectrum disorders. Despite the limited power to detect genes of minor effect with a low density SNPs, our data support a potential role of UBE3A in the complex pathogenic mechanisms of autism. To strengthen our findings, we are currently genotyping a denser set of SNPs across the region and using a larger sample, with the ultimate goal of identifying the specific polymorphism(s) responsible for the association