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. (June 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)
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: | June 2011 |
| Date Deposited: | 06 Feb 2013 19:49 |
| Last Modified: | 06 Feb 2013 19:49 |
| PMCID: | PMC3110052 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27151 |
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