Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk.
Copy number variations (CNVs) are a major cause of genetic disruption in the human genome with far more nucleotides being altered by duplications and deletions than by single nucleotide polymorphisms (SNPs). In the multifaceted etiology of autism spectrum disorders (ASDs), CNVs appear to contribute significantly to our understanding of the pathogenesis of this complex disease. A unique resource of 42 extended ASD families was genotyped for over 1 million SNPs to detect CNVs that may contribute to ASD susceptibility. Each family has at least one avuncular or cousin pair with ASD. Families were then evaluated for co-segregation of CNVs in ASD patients. We identified a total of five deletions and seven duplications in eleven families that co-segregated with ASD. Two of the CNVs overlap with regions on 7p21.3 and 15q24.1 that have been previously reported in ASD individuals and two additional CNVs on 3p26.3 and 12q24.32 occur near regions associated with schizophrenia. These findings provide further evidence for the involvement of ICA1 and NXPH1 on 7p21.3 in ASD susceptibility and highlight novel ASD candidates, including CHL1, FGFBP3 and POUF41. These studies highlight the power of using extended families for gene discovery in traits with a complex etiology.
John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, Florida, United States of America.
Daria
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Salyakina
Holly N
HN
Cukier
Joycelyn M
JM
Lee
Stephanie
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Sacharow
Laura D
LD
Nations
Deqiong
D
Ma
James M
JM
Jaworski
Ioanna
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Konidari
Patrice L
PL
Whitehead
Harry H
HH
Wright
Ruth K
RK
Abramson
Scott M
SM
Williams
Ramkumar
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Menon
Jonathan L
JL
Haines
John R
JR
Gilbert
Michael L
ML
Cuccaro
Margaret A
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Pericak-Vance
D000293:Adolescent; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D055815:Young Adult