Ellen M. Wijsman
Autism is a common developmental disorder with a prevalence of 2-5 per 10,000. Characteristic impairments include difficulty processing social and emotional information, language abnormalities, and repetitive or stereotyped behaviors. Additionally, 75% of autistic persons are mentally retarded. The etiology of autism is unknown, but evidence for inherited factors is strong. Monozygotic twins are frequently both affected while dizygotic twins have a lower concordance rate. Autism family studies show an elevated risk in sibs of probands relative to the general population. Genetic modeling suggests that the genetic component of autism is the result of multiple genes which interact (epistatic multigenic inheritance). Some unaffected parents and sibs exhibit some subclinical features related to autism which may reflect inheritance of some but not all of the aberrant genes required for the full autism phenotype.
We are working with data from >300 families with 2 or more affected sibs affected with autism. The autistic subjects have been rigorously evaluated to establish the diagnosis of autism and were given a battery of neurocognitive tests. We also have quantitative and semi-quantitative measures of neurocognitive function on both the affected sib pairs and their parents and one unaffected sibling for use in a quantitative trait locus (QTL) analysis approach to the genetic basis of autism. We are currently carrying out genome scans to identify position(s) of gene(s) involved in autism, including use of analytical methods that can be used for simultaneous analysis of multiple underlying trait loci. We also are now adding next generation sequence data to our sample
We are collaborators in the Autism Genome Project consortium, which is a large internation consortium that has combined data on both multiplex and simplex families. The hope is that larger sample sizes may yield information that cannot be obtained in smaller samples, and that this also will allow the sample to be divided into subgroups that may represent more homogenous groups. One such grouping, for example, involves combining the information from the extremely rare large pedigrees from this international collaboration.
Supported by NIH P50 HD 055782 "UW autism center of excellence" (B. King, PI), "Project 1: Genetic contributions to endophenotypes of autism" (E. Wijsman, PI), NIH R01 MH 092367 "Next generation gene discovery in familial autism" (Z. Brkanac, PI), and NIH R01 MH 094293 "Sequencing autism spectrum disorder extended pedigrees" (E. Wijsman, PI).