Mendelian inheritance of human disease is the exception rather than the rule. The vast majority of human disease has significant hereditary components and yet trait inheritance is distinctly non-Mendelian. It is commonly assumed that complex disease inheritance patterns arise from the interaction between multiple genetic and environmental factors but the molecular nature of the genetic variants is unknown. The search for thesesed complex genetic components depends on whether the underlying genetic effects are major or minor and whether the mutations are physically small or large on the genomic scale. For two decades we have used linkage analysis in complex disease families to map and identify major susceptibility genes but with little progress. Thus, for identifying the multiple minor components we need to develop technologies for genome-wide association studies. Classically, we have also assumed that genetic alterations in human disease are generally point mutations or small insertions/deletions. However, the human genome sequence suggests that segmental aneuploidy can underlie human disease. Consequently, we need technologies for identifying these genomic changes in human disease. Autism is a relatively common neuropsychiatric disorder with an incidence of approximately I in 1000 and genetic heritability of greater than 80%. Although the role of hereditary factors in autism is not in doubt their nature remains elusive and no single gene contributing to its etiology has been identified. Indeed, a recent study by Risch and colleagues emphasized that 15 or more segregating factors probably account for the increased intra-familial risk and that none of them are major factors. Consequently, we develop two types of genomic screens, one for single nucleotide polymorphisms (SNPs) and the other for genomic segmental aneuploidy, in the study of autism. In this proposal, we carry on the tradition from the previous funding cycle of developing novel genomic technologies that are of direct relevance to the genetic dissection of complex neuropsychiatric traits. [unreadable] [unreadable]