Abstract
Autism is a pervasive developmental disorder with a strong genetic component. While candidate regions of the genome have been identified, location of genes conferring susceptibility to autism has been hindered by the heterogeneity within this clinically defined disorder, and the likely contribution of many genes of weak effect. Subsetting samples on the basis of distinct, nondiagnostic clinical features has been recommended to decrease sample heterogeneity. In this study, linkage analysis was performed on a subset of families in the database of the Autism Genetic Resource Exchange (AGRE). This set of autism-affected relative pairs (n=34) was also concordant for a history of developmental regression as measured by the Autism Diagnostic Interview—Revised (ADI-R). In this sample, a maximum multipoint LOD score of 3.4 under the dominant mode of inheritance and an NPL score of 3.0 (P=1.3 × 10−3) were observed on chromosome 21 near D21S1437. On chromosome 7 near D7S483 a LOD score of 2.0 under the dominant mode of inheritance and an NPL score of 3.7 (P=7.9 × 10−5) were observed. Genetic elements in these regions of 21q and 7q are likely to confer susceptibility to autism or modify the disease presentation in a subgroup of children characterized by a history of developmental regression.
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Acknowledgements
We acknowledge support from the Autism Genetic Resource Exchange (AGRE) and Cure Autism Now. We gratefully acknowledge the resources provided by the AGRE consortium and the participating AGRE families. The Autism Genetic Resource Exchange (AGRE) is a program of Cure Autism Now and is supported, in part, by grant MH64547 from the National Institute of Mental Health to Daniel H Geschuind (PI). We gratefully acknowledge the thoughtful review of this manuscript by Ardythe L Morrow, PhD and the contribution of Li Jin, PhD in the preliminary discussion of these analyses.
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Molloy, C., Keddache, M. & Martin, L. Evidence for linkage on 21q and 7q in a subset of autism characterized by developmental regression. Mol Psychiatry 10, 741–746 (2005). https://doi.org/10.1038/sj.mp.4001691
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DOI: https://doi.org/10.1038/sj.mp.4001691
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