Human Molecular Genetics Advance Access originally published online on March 21, 2007
Human Molecular Genetics 2007 16(6):704-715; doi:10.1093/hmg/ddm015
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High density SNP association study of a major autism linkage region on chromosome 17
1 Department of Human Genetics, 2 Department of Neurology, 3 Program in Neurobiology, 4 Center for Neurobehavioral Genetics and 5 Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, CA, USA
* To whom correspondence should be addressed at: 695 Charles Young Drive South, Gonda Building, Room 5554, Los Angeles, CA 90095, USA. Tel: +1 3107947981; Fax: +1 3107945446; Email: snelson{at}ucla.edu
Received December 4, 2006; Revised January 31, 2007; Accepted February 2, 2007
A region on chromosome 17 has recently been highlighted as linked to autism (MIM[209850]) in multiple studies and evidence has accumulated suggesting that male-only families (those families that have produced only affected males) provide the major contribution to linkage at this locus. In an attempt to comprehensively test for association of common variants to autism within the region on chromosome 17 defined in Stone et al. (Stone, J.L., Merriman, B., Cantor, R.M., Yonan, A.L., Gilliam, T.C., Geschwind, D.H. and Nelson, S.F. (2004) Evidence for sex-specific risk alleles in autism spectrum disorder. Am. J. Hum. Genet., 75, 1117–1123), a dense panel of single nucleotide polymorphisms (SNPs) was selected across the linkage peak and analyzed in a trio-based study design. SNPs were genotyped in 219 independent trios at an average intermarker distance of 6.1 kb across the 13.7 Mb interval. This provided ~80% coverage of common HapMap variation present in Caucasians, testing exonic, intronic, promoter and intergenic regions, as knowledge of important functional regions within the genome is currently limited. In this comprehensive association study of a linkage region in autism, no single SNP or haplotype association was sufficient to account for the initial linkage signal. Nominally significant single SNP and/or haplotype-based association results were detected in 15 genes, of which, MYO1D, ACCN1 and LASP1 stand out as genes with autism risk alleles requiring further study, with potential GRRs in the range of 1.34–2.29.
Present address: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA