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Comparative Study
. 2006 Nov;11(11):1049-60, 979.
doi: 10.1038/sj.mp.4001874. Epub 2006 Aug 1.

Evidence for multiple loci from a genome scan of autism kindreds

G D Schellenberg  1 , G Dawson, Y J Sung, A Estes, J Munson, E Rosenthal, J Rothstein, P Flodman, M Smith, H Coon, L Leong, C-E Yu, C Stodgell, P M Rodier, M A Spence, N Minshew, W M McMahon, E M Wijsman
Affiliations
Comparative Study

Evidence for multiple loci from a genome scan of autism kindreds

G D Schellenberg et al. Mol Psychiatry. 2006 Nov.

Abstract

We performed a genome-wide linkage scan using highly polymorphic microsatellite markers. To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis of autism. In our primary analyses, we observed a strong linkage signal (P=0.0006, 133.16 cM) on chromosome 7q at a location coincident with other linkage studies. When a more relaxed diagnostic criteria was used, linkage evidence at this location was weaker (P=0.01). The sample was stratified into families with only male affected subjects (MO) and families with at least one female affected subject (FC). The strongest signal unique to the MO group was on chromosome 11 (P=0.0009, 83.82 cM), and for the FC group on chromosome 4 (P=0.002, 111.41 cM). We also divided the sample into regression positive and regression negative families. The regression-positive group showed modest linkage signals on chromosomes 10 (P=0.003, 0 cM) and 14 (P=0.005, 104.2 cM). More significant peaks were seen in the regression negative group on chromosomes 3 (P=0.0002, 140.06 cM) and 4 (P=0.0005, 111.41 cM). Finally, we used language acquisition data as a quantitative trait in our linkage analysis and observed a chromosome 9 signal (149.01 cM) of P=0.00006 and an empirical P-value of 0.0008 at the same location. Our work provides strong conformation for an autism locus on 7q and suggestive evidence for several other chromosomal locations. Diagnostic specificity and detailed analysis of the autism phenotype is critical for identifying autism loci.

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