Two independent lines of evidence indicate that the maternal immune system and a functional genetic variant contribute to autism spectrum disorder (ASD) risk. Here, in a unique collaborative effort, the Van De Water lab will parter with scientists at Vanderbilt University to examine whether these two seemingly unrelated contributions may converge to define a unique ASD susceptibility. Preliminary evidence collected by the Van De Water lab indicates an association between the MET gene ‘C' type, which reduces MET protein expression, and the presence of specific maternal anti-fetal brain autoantibodies. This relationship suggests that this as a pathway for production of the maternal autoantibodies, leading to a gene x environment interaction underlying ASD susceptibility. The next line of experiments will examine the relationship in an even larger sample, and assess the functional effect of the MET gene polymorphism on immune cell activity, and to further examine the impact of environmental toxins (including ethyl mercury) on the gene expression-dependent function of maternal immune cells. What this means for people with autism: This proposal thus brings together two initially unrelated findings (associations of the MET gene and maternal autoantibodies with ASD), and further tests specific functional hypotheses concerning gene-environment interactions, that may converge to define a unique cause of autism in some children.