title: Identification of risk genes for autism spectrum disorder through copy number variation analysis in Austrian families.
abstract: Autism or autism spectrum disorder (ASD) is a range of neurodevelopmental disorders starting in early childhood and is characterized by impairments in communication and reciprocal social interaction and presence of restricted and repetitive patterns of behavior. The contribution of genetic factors to autism is clear in twin and family studies. It is apparent that, overall, ASD is a complex non-Mendelian disorder. Recent studies suggest that copy number variations (CNVs) play a significant role in the etiology of ASD. For the current work, we recruited 245 family members from 73 ASD families from Styria, Austria. The DNA from probands was genotyped with Affymetrix single nucleotide polymorphism (SNP) 6.0 microarrays to screen for CNVs in their genomes. Analysis of the microarray data was performed using three different algorithms, and a list of stringent calls was compared to existing CNV data from over 2,357 controls of European ancestry. For stringent calls not present in controls, quantitative real-time PCR (qRT-PCR) was used to validate the CNVs in the probands and in their family members. Twenty-two CNVs were validated from this set (five of which are apparently de novo), many of which appear likely to disrupt genes that may be considered as good candidates for neuropsychiatric disorders, including DLG2, S100B, ARX, DIP2A, HPCAL1, and GPHN. Several others disrupt genes that have previously been implicated in autism, such as BDNF, AUTS2, DPP6, and C18orf22, and our data add to the growing evidence of their involvement in ASD.
authors.affiliation: Neurogenetics Section, R-30, The Campbell Family Brain Research Institute, The Centre for Addiction & Mental Health (CAMH), 250 College Street, Toronto, ON, M5T 1R8, Canada.
authors.forename: Gerald
authors.initials: G
authors.lastname: Egger
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Roetzer
authors.forename: Abdul
authors.initials: A
authors.lastname: Noor
authors.forename: Anath C
authors.initials: AC
authors.lastname: Lionel
authors.forename: Huda
authors.initials: H
authors.lastname: Mahmood
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarzbraun
authors.forename: Oliver
authors.initials: O
authors.lastname: Boright
authors.forename: Anna
authors.initials: A
authors.lastname: Mikhailov
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.forename: Christian
authors.initials: C
authors.lastname: Windpassinger
authors.forename: Erwin
authors.initials: E
authors.lastname: Petek
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kaschnitz
authors.forename: John B
authors.initials: JB
authors.lastname: Vincent
mesh_terms: D001317:Austria; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors