title: Reduced transcript expression of genes affected by inherited and de novo CNVs in autism.
abstract: Individuals with autism are more likely to carry rare inherited and de novo copy number variants (CNVs). However, further research is needed to establish which CNVs are causal and the mechanisms by which these CNVs influence autism. We examined genomic DNA of children with autism (N = 41) and healthy controls (N = 367) for rare CNVs using a high-resolution array comparative genomic hybridization platform. We show that individuals with autism are more likely to harbor rare CNVs as small as ∼ 10 kb, a threshold not previously detectable, and that CNVs in cases disproportionately affect genes involved in transcription, nervous system development, and receptor activity. We also show that a subset of genes that have known or suspected allele-specific or imprinting effects and are within rare-case CNVs may undergo loss of transcript expression. In particular, expression of CNTNAP2 and ZNF214 are decreased in probands compared with their unaffected transmitting parents. Furthermore, expression of PRODH and ARID1B, two genes affected by de novo CNVs, are decreased in probands compared with controls. These results suggest that for some genes affected by CNVs in autism, reduced transcript expression may be a mechanism of pathogenesis during neurodevelopment.
authors: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. nordalex@u.washington.edu
authors: Alex S
authors: AS
authors: Nord
authors: Wendy
authors: W
authors: Roeb
authors: Diane E
authors: DE
authors: Dickel
authors: Tom
authors: T
authors: Walsh
authors: Mary
authors: M
authors: Kusenda
authors: Kristen Lewis
authors: KL
authors: O'Connor
authors: Dheeraj
authors: D
authors: Malhotra
authors: Shane E
authors: SE
authors: McCarthy
authors: Sunday M
authors: SM
authors: Stray
authors: Susan M
authors: SM
authors: Taylor
authors: Jonathan
authors: J
authors: Sebat
authors: Bryan
authors: B
authors: King
authors: Mary-Claire
authors: MC
authors: King
authors: Jon M
authors: JM
authors: McClellan
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D055028:Comparative Genomic Hybridization; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D015894:Genome, Human; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011394:Proline Oxidase / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C497837:ARID1B protein, human; C403049:CNTNAP2 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C409745:ZNF214 protein, human; D011394:Proline Oxidase