Strategies for autism candidate gene analysis

The identification of autism susceptibility genes has moved a step closer over the last four years with the completion of eight whole genome screens for linkage. Several overlapping areas of linkage have been reported, most notably on chromosomes 7q22-31 and 2q32. These regions of replicated linkage provide a focus to search for candidate genes whose normal functions in neurodevelopment are altered to increase the risk for autism. Strategies that aim to narrow further the rather broad size of these linkage regions, such as high density single nucleotide polymorphism (SNP)-based association studies, currently suffer from practical and statistical limitations. Alternatively, positional candidate genes can be screened for deleterious variants in autistic individuals selected from large samples such as those collected by the International Molecular Genetic Study of Autism Consortium (IMGSAC). Targeted genotyping of candidate gene variants in this large multiplex family sample will then be performed to confirm association with autism.