Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder
Journal
Molecular Autism
Journal Volume
7
Journal Issue
1
Date Issued
2016
Author(s)
Yin C.-L.
Chen H.-I.
Li L.-H.
Liao H.-M.
Chou M.C.
Chou W.-J.
Wu Y.-Y.
Lo C.-Z.
Wu J.-Y.
Chen Y.-T.
Abstract
Background: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population. Methods: To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR). Results: A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene. Conclusions: Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene. ? 2016 Yin et al.
SDGs
Other Subjects
Article; autism; child; Chinese; controlled study; copy number variation; down regulation; exon; female; gene; gene deletion; gene disruption; gene duplication; gene expression; gene function; gene locus; genome-wide association study; human; human cell; major clinical study; male; PARK2 gene; preschool child; priority journal; school child; single nucleotide polymorphism; adolescent; Asian continental ancestry group; Autism Spectrum Disorder; China; cohort analysis; genetics; genotype; odds ratio; pedigree; phenotype; parkin; ubiquitin protein ligase; Adolescent; Asian Continental Ancestry Group; Autism Spectrum Disorder; Child; China; Cohort Studies; DNA Copy Number Variations; Down-Regulation; Exons; Female; Genome-Wide Association Study; Genotype; Humans; Male; Odds Ratio; Pedigree; Phenotype; Polymorphism, Single Nucleotide; Ubiquitin-Protein Ligases
Publisher
BioMed Central Ltd.
Type
journal article