Copy Number Variants in Extended Autism Spectrum Disorder Families Reveal Candidates Potentially Involved in Autism Risk
Open Access
- 7 October 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (10), e26049
- https://doi.org/10.1371/journal.pone.0026049
Abstract
Copy number variations (CNVs) are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than by single nucleotide polymorphisms (SNPs). In the multifaceted etiology of autism spectrum disorders (ASDs), CNVs appear to contribute significantly to our understanding of the pathogenesis of this complex disease. A unique resource of 42 extended ASD families was genotyped for over 1 million SNPs to detect CNVs that may contribute to ASD susceptibility. Each family has at least one avuncular or cousin pair with ASD. Families were then evaluated for co-segregation of CNVs in ASD patients. We identified a total of five deletions and seven duplications in eleven families that co-segregated with ASD. Two of the CNVs overlap with regions on 7p21.3 and 15q24.1 that have been previously reported in ASD individuals and two additional CNVs on 3p26.3 and 12q24.32 occur near regions associated with schizophrenia. These findings provide further evidence for the involvement of ICA1 and NXPH1 on 7p21.3 in ASD susceptibility and highlight novel ASD candidates, including CHL1, FGFBP3 and POUF41. These studies highlight the power of using extended families for gene discovery in traits with a complex etiology.Keywords
This publication has 49 references indexed in Scilit:
- Rare structural variation of synapse and neurotransmission genes in autismMolecular Psychiatry, 2011
- CALL interrupted in a patient with non-specific mental retardation: gene dosage-dependent alteration of murine brain development and behavior.Human Molecular Genetics, 2003
- First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlationAmerican Journal of Medical Genetics, 2001
- Impaired cerebral cortex development and blood pressure regulation in FGF-2-deficient miceThe EMBO Journal, 1998
- Neurexophilins Form a Conserved Family of Neuropeptide-Like GlycoproteinsJournal of Neuroscience, 1998
- The Brn-3 family of POU-domain factors: primary structure, binding specificity, and expression in subsets of retinal ganglion cells and somatosensory neuronsJournal of Neuroscience, 1995
- Psychiatric Disorders in the Parents of Autistic IndividualsJournal of the American Academy of Child & Adolescent Psychiatry, 1991
- A Twin Study of Autism in Denmark, Finland, Iceland, Norway and SwedenJournal of Child Psychology and Psychiatry, 1989
- Concordance for the syndrome of autism in 40 pairs of afflicted twinsAmerican Journal of Psychiatry, 1985
- INFANTILE AUTISM: A GENETIC STUDY OF 21 TWIN PAIRSJournal of Child Psychology and Psychiatry, 1977