title: Association between microdeletion and microduplication at 16p11.2 and autism.
abstract: BACKGROUND
  Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role.
  
  
  METHODS
  As a first component of a genomewide association study of families from the Autism Genetic Resource Exchange (AGRE), we used two novel algorithms to search for recurrent copy-number variations in genotype data from 751 multiplex families with autism. Specific recurrent de novo events were further evaluated in clinical-testing data from Children's Hospital Boston and in a large population study in Iceland.
  
  
  RESULTS
  Among the AGRE families, we observed five instances of a de novo deletion of 593 kb on chromosome 16p11.2. Using comparative genomic hybridization, we observed the identical deletion in 5 of 512 children referred to Children's Hospital Boston for developmental delay, mental retardation, or suspected autism spectrum disorder, as well as in 3 of 299 persons with autism in an Icelandic population; the deletion was also carried by 2 of 18,834 unscreened Icelandic control subjects. The reciprocal duplication of this region occurred in 7 affected persons in AGRE families and 4 of the 512 children from Children's Hospital Boston. The duplication also appeared to be a high-penetrance risk factor.
  
  
  CONCLUSIONS
  We have identified a novel, recurrent microdeletion and a reciprocal microduplication that carry substantial susceptibility to autism and appear to account for approximately 1% of cases. We did not identify other regions with similar aggregations of large de novo mutations.
authors.affiliation: Autism Consortium , Boston, USA.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Weiss
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Korn
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
authors.forename: David T
authors.initials: DT
authors.lastname: Miller
authors.forename: Ragnheidur
authors.initials: R
authors.lastname: Fossdal
authors.forename: Evald
authors.initials: E
authors.lastname: Saemundsen
authors.forename: Hreinn
authors.initials: H
authors.lastname: Stefansson
authors.forename: Manuel A R
authors.initials: MA
authors.lastname: Ferreira
authors.forename: Todd
authors.initials: T
authors.lastname: Green
authors.forename: Orah S
authors.initials: OS
authors.lastname: Platt
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Ruderfer
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
authors.forename: David
authors.initials: D
authors.lastname: Altshuler
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Susan L
authors.initials: SL
authors.lastname: Santangelo
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Pamela
authors.initials: P
authors.lastname: Sklar
authors.forename: Bai-Lin
authors.initials: BL
authors.lastname: Wu
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
mesh_terms: D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D010641:Phenotype; D017422:Sequence Analysis, DNA / Q000379:methods