High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L–DOCK4 gene region in autism susceptibility
Year: 2009
Type: article
Study design: Observational Study
Abstract: Autism spectrum disorders are a group of highly heritable neurodevelopmental disorders with a complex genetic etiology. The International Molecular Genetic Study of Autism Consortium previously identified linkage loci on chromosomes 7 and 2, termed AUTS1 and AUTS5, respectively. In this study, we performed a high-density association analysis in AUTS1 and AUTS5, testing more than 3000 single nucleotide polymorphisms (SNPs) in all known genes in each region, as well as SNPs in non-genic highly conserved sequences. SNP genotype data were also used to investigate copy number variation within these regions. The study sample consisted of 127 and 126 families, showing linkage to the AUTS1 and AUTS5 regions, respectively, and 188 gender-matched controls. Further investigation of the strongest association results was conducted in an independent European family sample containing 390 affected individuals. Association and copy number variant analysis highlighted several genes that warrant further investigation, including IMMP2L and DOCK4 on chromosome 7. Evidence for the involvement of DOCK4 in autism susceptibility was supported by independent replication of association at rs2217262 and the finding of a deletion segregating in a sib-pair family.
Source: Molecular Psychiatry
DOI: 10.1038/mp.2009.34
Authors: IMGSAC, E Maestrini, A T Pagnamenta, J A Lamb, E Bacchelli, N H Sykes, I Sousa, C Toma, G Barnby, H Butler, L Winchester, T S Scerri, F Minopoli, J Reichert, G Cai, J D Buxbaum, O Korvatska, G D Schellenberg, G Dawson, A de Bildt, R B Minderaa, E J Mulder, A P Morris, A J Bailey, A P Monaco
Institutions: University of Bologna, Centre for Human Genetics, University of Oxford, University of Manchester, Icahn School of Medicine at Mount Sinai, VA Puget Sound Health Care System, University of Pennsylvania, Autism Speaks, University of Washington, University Medical Center Groningen, Warneford Hospital
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,490
Funders: Simons Foundation, Nancy Lurie Marks Family Foundation, Sundhed og Sygdom, Det Frie Forskningsråd, Wellcome Trust, Deutsche Forschungsgemeinschaft, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Università di Bologna, National Institutes of Health, Medical Research Council, National Institute of Mental Health, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Mapping and characterisation of susceptibility genes in multifactorial diseases - Bioinformatics, Neurobiology and genetics of Autism & Related Conditions, GENERAL CLINICAL RESEARCH CENTER, Statistical methods for the analysis of whole genome association studies., Identification and functional analysis of susceptibility genes in multifactorial disease., Whole genome strategies for detecting and characterizing complex trait loci., MOLECULAR GENETIC STUDIES OF CHILD PSYCHOPATHOLOGY, DIAGNOSIS AND FOLLOWUP STUDIES OF AUTISTIC CHILDREN, G9000261490
OpenAlex ID: W2121045992