Human Molecular Genetics Advance Access originally published online on May 19, 2009
Human Molecular Genetics 2009 18(15):2912-2921; doi:10.1093/hmg/ddp229
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Linkage and linkage disequilibrium scan for autism loci in an extended pedigree from Finland
1 Department of Molecular Medicine, Institute for Molecular Medicine, Finland (FIMM), National Public Health Institute, Biomedicum, Haartmaninkatu 8 00251, Helsinki, Finland 2 Department of Medical Genetics, University of Helsinki, Biomedicum, Haartmaninkatu 8 00251, Helsinki, Finland 3 Unit of Child Neurology, Hospital for Children and Adolescents, Lastenlinnantie 2 00029 HUS, Helsinki, Finland 4 The Broad Institute, MIT and Harvard University, 7 Cambridge Center, Cambridge, MA 02141-2023, USA 5 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
* To whom correspondence should be addressed. Tel: +44 1223496845; Fax: +44 1223496826; Email: leena{at}sanger.ac.uk or leena.peltonen{at}thl.fi
Received February 17, 2009; Accepted May 11, 2009
Population isolates, such as Finland, have proved beneficial in mapping rare causative genetic variants due to a limited number of founders resulting in reduced genetic heterogeneity and extensive linkage disequilibrium (LD). We have here used this special opportunity to identify rare alleles in autism by genealogically tracing 20 autism families into one extended pedigree with verified genealogical links reaching back to the 17th century. In this unique pedigree, we performed a dense microsatellite marker genome-wide scan of linkage and LD and followed initial findings with extensive fine-mapping. We identified a putative autism susceptibility locus at 19p13.3 and obtained further evidence for previously identified loci at 1q23 and 15q11–q13. Most promising candidate genes were TLE2 and TLE6 clustered at 19p13 and ATP1A2 at 1q23.