Copy number variations independently induce autism spectrum disorder

Abstract

Correspondence : Sun Xiaofang (xiaofangsun@hotmail.com) The examination of copy number variation (CNV) is critical to understand the etiology of the CNV-related autism spectrum disorders (ASD). DNA samples were obtained from 64 ASD probands, which were genotyped on an Affymetrix CytoScan HD platform. qPCR or FISH were used as a validation for some novel recurrent CNVs. We further compared the clinical phenotypes of the genes in the Database of Chromosomal Imbalance and Phenotype in Humans Using Ensembl Resources (DECIPHER) database with these overlapping genes. Using vast, readily available databases with previously reported clinically relevant CNVs from human populations, the genes were evaluated using Enrichment Analysis and GO Slim Classification. By using the Ploysearch2 software, we identified the interaction relationship between significant genes and known ASD genes. A total of 29 CNVs, overlapping with 520 genes, including 315 OMIM genes, were identified. Additionally, myocyte enhancer factor 2 family (MEF2C) with two cases of CNV overlapping were also identified. Enrichment analysis showed that the 520 genes are most likely to be related to membrane components with protein-binding functions involved in metabolic processes. In the interaction network of those genes, the known ASD genes are mostly at the core position and the significant genes found in our samples are closely related to the known ASD genes. CNVs should be an independent factor to induce autism. With the strategy of our study, we could find the ASDs candidate genes by CNV data and review certain pathogenesis of this disorder. Those CNVs were associated with ASD and they may contribute to ASD by affecting the ASD-related genes.

Investigation of Copy Number Variation by arrayCGH in Turkish Children and Adolescents Diagnosed with Autism Spectrum Disorders

“…Harrison et al stated that autism diagnosis and heterozygous NRXN1 deletion in female twin is associated (12). Xie et al in their recent study determined a microduplication in CHRNA7 gene, mapped at 15q13.3 chromosomal region, in a case clinically diagnosed as autism spectrum disorder (14). Partial NRXN1 deletion found in our two independent patients supports these studies.…”

MCKAT, a multi-dimensional copy number variant kernel association test

“…All CNV features including chromosomal position, type and dosage are used to measure the similarity between a single pair CNV. Let X = (X (1) , X (2) , X (3) , X (4) ) denote a CNV, where X (1) and X (2) are the start and end chromosomal positions of the CNV respectively, X (3) is the type information of the CNV taking the value 1 for a deletion and 3 for a amplification, and X (4) is the dosage information of the CNV taking the value of 0 or 1 for deletion, and > 2 for amplification. Considering two arbitrary CNVs X 1 and X 2 , we define the kernel function between a CNV pair as…”

“…2 The Tumour Bank, The Children's Hospital at Westmead, Sydney, AU. 3 Center for Cancer Research, National Cancer Institute, Bethesda, USA.…”

“…The second CNV group is rare variants that are much longer than CNPs, ranging from hundreds of thousands of base pairs to over 1 million base pairs. Studies have detected large structural variants in patients with a disease like mental retardation, developmental delay, schizophrenia, and autism [2][3][4][5][6][7][8][9][10][11].…”

Copy number variations (CNVs) in Brazilian patients with autism spectrum disorder (ASD)

“…Taken together, our data can add to better understanding PMS. Yingjun et al 2017). It is estimated that it affects roughly 1% of the world population and the majority of these cases (about 75%) remain unsolved .…”