Genome-wide linkage in Utah autism pedigrees.
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ABSTRACT:
SUBMITTER: Allen-Brady K
PROVIDER: S-EPMC4023913 | biostudies-literature | 2010 Oct
REPOSITORIES: biostudies-literature
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Genome-wide linkage in Utah autism pedigrees.
Allen-Brady K K Robison R R Cannon D D Varvil T T Villalobos M M Pingree C C Leppert M F MF Miller J J McMahon W M WM Coon H H
Molecular psychiatry 20090519 10
Genetic studies of autism over the past decade suggest a complex landscape of multiple genes. In the face of this heterogeneity, studies that include large extended pedigrees may offer valuable insights, as the relatively few susceptibility genes within single large families may be more easily discerned. This genome-wide screen of 70 families includes 20 large extended pedigrees of 6-9 generations, 6 moderate-sized families of 4-5 generations and 44 smaller families of 2-3 generations. The Cente ...[more]
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Project description:Autism is a common heritable neurodevelopmental disorder with complex etiology. Several genome-wide linkage and association scans have been carried out to identify regions harboring genes related to autism or autism spectrum disorders, with mixed results. Given the overlap in autism features with genetic abnormalities known to be associated with imprinting, one possible reason for lack of consistency would be the influence of parent-of-origin effects that may mask the ability to detect linkage and association.We have performed a genome-wide linkage scan that accounts for potential parent-of-origin effects using 16,311 SNPs among families from the Autism Genetic Resource Exchange (AGRE) and the National Institute of Mental Health (NIMH) autism repository. We report parametric (GH, Genehunter) and allele-sharing linkage (Aspex) results using a broad spectrum disorder case definition. Paternal-origin genome-wide statistically significant linkage was observed on chromosomes 4 (LOD(GH) = 3.79, empirical p<0.005 and LOD(Aspex) = 2.96, p = 0.008), 15 (LOD(GH) = 3.09, empirical p<0.005 and LOD(Aspex) = 3.62, empirical p = 0.003) and 20 (LOD(GH) = 3.36, empirical p<0.005 and LOD(Aspex) = 3.38, empirical p = 0.006).These regions may harbor imprinted sites associated with the development of autism and offer fruitful domains for molecular investigation into the role of epigenetic mechanisms in autism.
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