Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
18184952
TITLE
Association between microdeletion and microduplication at 16p11.2 and autism.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Autism spectrum disorder is a heritable developmental disorder in which chromosomal abnormalities are thought to play a role.
METHODS NlmCategory: 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 NlmCategory: 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 NlmCategory: 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.
Copyright 2008 Massachusetts Medical Society.
DATE PUBLISHED
2008 Feb 14
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2008/01/09
pubmed 2008/01/11 09:00
medline 2008/02/20 09:00
entrez 2008/01/11 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Weiss LA Weiss Lauren A LA Autism Consortium , Boston, USA.
Shen Y Shen Yiping Y
Korn JM Korn Joshua M JM
Arking DE Arking Dan E DE
Miller DT Miller David T DT
Fossdal R Fossdal Ragnheidur R
Saemundsen E Saemundsen Evald E
Stefansson H Stefansson Hreinn H
Ferreira MA Ferreira Manuel A R MA
Green T Green Todd T
Platt OS Platt Orah S OS
Ruderfer DM Ruderfer Douglas M DM
Walsh CA Walsh Christopher A CA
Altshuler D Altshuler David D
Chakravarti A Chakravarti Aravinda A
Tanzi RE Tanzi Rudolph E RE
Stefansson K Stefansson Kari K
Santangelo SL Santangelo Susan L SL
Gusella JF Gusella James F JF
Sklar P Sklar Pamela P
Wu BL Wu Bai-Lin BL
Daly MJ Daly Mark J MJ
Autism Consortium
INVESTIGATORS
JOURNAL
VOLUME: 358
ISSUE: 7
TITLE: The New England journal of medicine
ISOABBREVIATION: N. Engl. J. Med.
YEAR: 2008
MONTH: Feb
DAY: 14
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1533-4406
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: N Engl J Med
COUNTRY: United States
ISSNLINKING: 0028-4793
NLMUNIQUEID: 0255562
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
CommentIn N Engl J Med. 2008 Feb 14;358(7):737-9 18184953
GRANTS
GRANTID AGENCY COUNTRY
R01-MN071425-01A1 OMHHE CDC HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Autistic Disorder genetics
Child genetics
Chromosome Aberrations genetics
Chromosome Deletion genetics
Chromosomes, Human, Pair 15 genetics
Chromosomes, Human, Pair 16 genetics
DNA Mutational Analysis genetics
Developmental Disabilities genetics
Female genetics
Genetic Predisposition to Disease genetics
Genotype genetics
Humans genetics
Intellectual Disability genetics
Male genetics
Phenotype genetics
Sequence Analysis, DNA methods
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's