Abstract
Rare genomic copy number variations (CNVs) (frequency <1%) contribute a part to the genetic underpinnings of autism spectrum disorders (ASD). The study aimed to understand the scope of rare CNV in Taiwanese patients with ASD. We conducted a genome-wide CNV screening of 335 ASD patients (299 males, 36 females) from Taiwan using Affymetrix Genome-Wide Human SNP Array 6.0 and compared the incidence of rare CNV with that of 1093 control subjects (525 males, 568 females). We found a significantly increased global burden of rare CNVs in the ASD group compared to the controls as a whole or when the rare CNVs were classified by the size and types of CNV. Further analysis confirmed the presence of several rare CNVs at regions strongly associated with ASD as reported in the literature in our sample. Additionally, we detected several new private pathogenic CNVs in our samples and five patients carrying two pathogenic CNVs. Our data indicate that rare genomic CNVs contribute a part to the genetic landscape of our ASD patients. These CNVs are highly heterogeneous, and the clinical interpretation of the pathogenic CNVs of ASD is not straightforward in consideration of the incomplete penetrance, varied expressivity, and individual genetic background.
Highlights
Autism spectrum disorder (ASD) represents a group of childhood-onset neurodevelopmental disorders characterized by abnormal social interactions, impaired verbal and nonverbal communication, and the presence of restricted interests and repetitive behaviors with long-term persistence of core features and functional impairment[1,2]
The recent advent of array-based comparative genomic hybridization technology has discovered various submicroscopic copy number variations (CNVs) of genomic DNA associated with ASD29,30, leading further support to the idea that autism spectrum disorders (ASD) is a genomic disorder in a subset of the patients
We investigated the ethnicity of cases and controls by performing principle component analysis (PCA) with single nucleotide polymorphisms (SNPs) genotype data from all the participants of this study and the individuals included in HapMap study
Summary
Autism spectrum disorder (ASD) represents a group of childhood-onset neurodevelopmental disorders characterized by abnormal social interactions, impaired verbal and nonverbal communication, and the presence of restricted interests and repetitive behaviors with long-term persistence of core features and functional impairment[1,2]. Conventional cytogenetic studies of ASD have revealed a variety of rare chromosomal abnormalities associated with ASD25–28 indicating aberrant genomic rearrangements are part of the genetic mechanism of ASD. The recent advent of array-based comparative genomic hybridization (aCGH) technology has discovered various submicroscopic copy number variations (CNVs) of genomic DNA associated with ASD29,30, leading further support to the idea that ASD is a genomic disorder in a subset of the patients. These ASD-associated CNVs are usually individually unique and of low frequency, but together they account for approximately 5–10% of idiopathic ASD29, constituting a part of the genetic architecture of ASD22,31,32. To have a better understanding of the scope of rare genomic CNVs in our ASD patient population, we recruited a sample of more than 300 ASD patients and conducted a genome-wide CNV screening in this sample
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