JHIBRG:Abstract Apr 17 2008

Different loci on most of the chromosomes have been identified as potential susceptibility genes for autism spectrum disorder (ASD) in previous genome-wide screens of multiplex families. To search for genes related to autism, many linkage analyses and association studies have been performed. To minimize the probable genetic heterogeneity, subgroup analyses were commonly performed. Based on previous finding that some individuals who had 1 or more family members with ASD were found to have low cholesterol levels, we hypothesized that ASD patients with hypocholesterolemia may have different genetic susceptibility loci than other ASD patients. We obtained genotypic data on 20 families with at least 2 children with either autism or other ASD who donated blood to the Autism Genetic Resource Exchange repository and had hypocholesterolemia. The data was from 20 probands and their first degree family members with 408 genotyped microsatellite markers, with cholesterol levels from 53 to 101 mg/dl. The probands were analyzed as 3 groups: 20 families with ASD, 8 families in which both sibs had autism, and 12 families in which one of the sibs had “Not Quite Autism” or “Broad Spectrum Autism”. In ASD families and NQA and BSA families, the promising markers are D17S871 (P value of NPL score = 0.013, Kong & Cox LOD= 1.97) at 17p11.2, D17S1824 (P value of NPL score = 0.002, Kong & Cox LOD =1.68), and D17S1800 (P value of NPL score = 0.003, Kong & Cox LOD = 1.37) at 17q11.2. In autism families, D3S3728 (Kong & Cox LOD =2.02) and D3S4545 (Kong & Cox LOD = 2.11) at 3p26.1 have less than 7.4 x 10-4 P values, which show suggestive linkage evidence for sib pair analysis. In summary, we find several intriguing markers on chromosome 17 that may code for the serotonin transporter gene and for the sterol regulatory binding protein. Two markers at 3p26.1 region may code for the oxytocin receptor and metabotropic glutamate receptor 7(mGluR7). These identified loci can support the cure of autism and future public health implication of autism population.

Keywords: autism, hypocholesterolemia, genetic mapping, nonparametric linkage analysis