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

Alexander Nord, Wendy Roeb, Diane E. Dickel, Tom Walsh, Mary Kusenda, Kristen Lewis O'Connor, Dheeraj Malhotra, Shane E. McCarthy, Sunday M. Stray, Susan M. Taylor, Jonathan Sebat, Bryan King, Mary Claire King, Jon M. McClellan

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


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 (N41) and healthy controls (N367) 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.

Original languageEnglish (US)
Pages (from-to)727-731
Number of pages5
JournalEuropean Journal of Human Genetics
Issue number6
StatePublished - Jun 1 2011
Externally publishedYes


  • aCGH
  • autism
  • CNV
  • deletion
  • duplication
  • expression

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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