Rare de novo and transmitted copy-number variation in autistic spectrum disorders

Neuron. 2011 Jun 9;70(5):886-97. doi: 10.1016/j.neuron.2011.05.015.


To explore the genetic contribution to autistic spectrum disorders (ASDs), we have studied genomic copy-number variation in a large cohort of families with a single affected child and at least one unaffected sibling. We confirm a major contribution from de novo deletions and duplications but also find evidence of a role for inherited "ultrarare" duplications. Our results show that, relative to males, females have greater resistance to autism from genetic causes, which raises the question of the fate of female carriers. By analysis of the proportion and number of recurrent loci, we set a lower bound for distinct target loci at several hundred. We find many new candidate regions, adding substantially to the list of potential gene targets, and confirm several loci previously observed. The functions of the genes in the regions of de novo variation point to a great diversity of genetic causes but also suggest functional convergence.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child Development Disorders, Pervasive / genetics*
  • Child, Preschool
  • DNA Copy Number Variations / genetics*
  • Databases, Nucleic Acid / statistics & numerical data
  • Family Health*
  • Female
  • Gene Deletion*
  • Gene Expression Profiling
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Models, Statistical
  • Neurotransmitter Agents / genetics*
  • Oligonucleotide Array Sequence Analysis / methods
  • Phenotype
  • Probability
  • Siblings


  • Neurotransmitter Agents

Associated data

  • GEO/GSE23682