So far the search for genetic factors responsible for ASD has been carried out by global linkage and most recently by genome-wide association (GWA) studies clearly dominated by pooling patient collections containing cases with autism, Asperger, high functioning autism, and PDD-NOS. As result, there have been more than ten whole-genome screens world-wide with suggestive linkage findings for 19 of the autosomal and the X chromosome. Even though linkage and GWA studies are the most widely used approach to relate genetic variation to phenotypic diversity, they have several limitations.

Exome sequencing is a preferable strategy for identifying disease susceptibility loci as the clear majority of allelic variants known to underlie mendelian disorders disrupt protein-coding sequences, splice acceptor and donor sites. A large fraction of rare non-synonymous variants in the human genome are predicted to be deleterious in contrast to non-coding sequences, where variants are more likely to have neutral or weak effects on phenotypes.

In collaboration with PD Dr. Sabine Klauck at the German Cancer Research Center (DKFZ), MD Dr. Luise Poustka at the Central Institute of Mental Health-ZI Mannheim and Prof. Dr. med. Fritz Poustka affiliated with the Wolfgang Goethe University at Frankfurt, we intend to participate in projects generating exone sequence data from autism patients and develop animal model systems for autism.