Reduced transcript expression of genes affected by inherited and de novo CNVs in autism

Nord, A. S., Roeb, W., Dickel, D. E., Walsh, T., Kusenda, M., O'Connor, K. L., Malhotra, D., McCarthy, S. E., Stray, S. M., Taylor, S. M., Sebat, J., King, B., King, M. C., McClellan, J. M. (2011) Reduced transcript expression of genes affected by inherited and de novo CNVs in autism. European Journal of Human Genetics, 19 (6). pp. 727-731. ISSN 10184813 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/21448237
DOI: 10.1038/ejhg.2011.24

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.European Journal of Human Genetics advance online publication, 30 March 2011; doi:10.1038/ejhg.2011.24.

Item Type: Paper
Uncontrolled Keywords: COPY NUMBER VARIATION SPECTRUM DISORDER SCHIZOPHRENIA CNTNAP2 GENOME REARRANGEMENTS MICRODELETION ASSOCIATION DISRUPTION PATHWAYS
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
diseases & disorders > mental disorders > personality disorders
diseases & disorders > mental disorders > personality disorders > autism
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants
CSHL Authors:
Communities: CSHL labs > McCombie lab
CSHL labs > Sebat lab
Depositing User: Matt Covey
Date Deposited: 06 Feb 2013 19:49
Last Modified: 06 Feb 2013 19:49
PMCID: PMC3110052
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27151

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