Overwhelming evidence from twin and sibling studies demonstrates that autism is highly heritable (Steffenburg et al. 1989, Bailey et al. 1995, Bolton et al. 1994), but there is no consensus on the underlying genetic architecture. There are two alternative proposals, one involving numerous rare genetic mutations and the other involving fewer but more common genetic variations. Supporting the rare mutation hypothesis are mutations in several genes and rare structural DNA variations both of which have been identified, although the pervasiveness of these effects remains controversial (Weiss et al. 2008, Sebat et al. 2007). Data supporting the effect of common variation has been more difficult to find. Several genome-wide linkage screens and focused candidate gene association studies have been performed in autism (Shao et al. 2002, Szatmari et al. 2007, International Molecular Genetic Study of Autism Consortium (IMGSAC) 2001), but the results have been disappointing and no universally accepted susceptibility polymorphism has yet emerged. Collectively these data have suggested that the common variant hypothesis may not be relevant to autism genetics.
