A unified genetic theory for sporadic and inherited autism

Xiaoyue Zhao, Anthony Leotta, Vlad Kustanovich, Clara Lajonchere, Daniel H. Geschwind, Kiely Law, Paul Law, Shanping Qiu, Catherine Lord, Jonathan Sebat, Kenny Ye, Michael Wigler

Research output: Contribution to journalArticlepeer-review

223 Scopus citations

Abstract

Autism is among the most clearly genetically determined of all cognitive-developmental disorders, with males affected more often than females. We have analyzed autism risk in multiplex families from the Autism Genetic Resource Exchange (AGRE) and find strong evidence for dominant transmission to male offspring. By incorporating generally accepted rates of autism and sibling recurrence, we find good fit for a simple genetic model in which most families fall into two types: a small minority for whom the risk of autism in male offspring is near 50%, and the vast majority for whom male offspring have a low risk. We propose an explanation that links these two types of families: sporadic autism in the low-risk families is mainly caused by spontaneous mutation with high penetrance in males and relatively poor penetrance in females; and high-risk families are from those offspring, most often females, who carry a new causative mutation but are unaffected and in turn transmit the mutation in dominant fashion to their offspring.

Original languageEnglish (US)
Pages (from-to)12831-12836
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number31
DOIs
StatePublished - Jul 31 2007

Keywords

  • Human genetics
  • Neurodevelopmental disorders
  • Population genetics

ASJC Scopus subject areas

  • General

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