• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.

Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs. Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with approximately 550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12), several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls (P = 9.5 x 10(-3)). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3.3 x 10(-3)). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 x 10(-6)). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.

Pubmed ID: 19404257

Authors

  • Glessner JT
  • Wang K
  • Cai G
  • Korvatska O
  • Kim CE
  • Wood S
  • Zhang H
  • Estes A
  • Brune CW
  • Bradfield JP
  • Imielinski M
  • Frackelton EC
  • Reichert J
  • Crawford EL
  • Munson J
  • Sleiman PM
  • Chiavacci R
  • Annaiah K
  • Thomas K
  • Hou C
  • Glaberson W
  • Flory J
  • Otieno F
  • Garris M
  • Soorya L
  • Klei L
  • Piven J
  • Meyer KJ
  • Anagnostou E
  • Sakurai T
  • Game RM
  • Rudd DS
  • Zurawiecki D
  • McDougle CJ
  • Davis LK
  • Miller J
  • Posey DJ
  • Michaels S
  • Kolevzon A
  • Silverman JM
  • Bernier R
  • Levy SE
  • Schultz RT
  • Dawson G
  • Owley T
  • McMahon WM
  • Wassink TH
  • Sweeney JA
  • Nurnberger JI
  • Coon H
  • Sutcliffe JS
  • Minshew NJ
  • Grant SF
  • Bucan M
  • Cook EH
  • Buxbaum JD
  • Devlin B
  • Schellenberg GD
  • Hakonarson H

Journal

Nature

Publication Data

May 28, 2009

Associated Grants

  • Agency: NIMH NIH HHS, Id: 1U24MH081810
  • Agency: NICHD NIH HHS, Id: HD055751
  • Agency: NICHD NIH HHS, Id: HD055782-01
  • Agency: NICHD NIH HHS, Id: HD35476
  • Agency: NCRR NIH HHS, Id: M01 RR000064-340579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-350579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-35S10579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-35S10591
  • Agency: NCRR NIH HHS, Id: M01 RR000064-35S10602
  • Agency: NCRR NIH HHS, Id: M01 RR000064-35S20579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-35S20591
  • Agency: NCRR NIH HHS, Id: M01 RR000064-35S20602
  • Agency: NCRR NIH HHS, Id: M01 RR000064-360579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-360582
  • Agency: NCRR NIH HHS, Id: M01 RR000064-360591
  • Agency: NCRR NIH HHS, Id: M01 RR000064-36S10579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-36S10582
  • Agency: NCRR NIH HHS, Id: M01 RR000064-36S10591
  • Agency: NCRR NIH HHS, Id: M01 RR000064-370579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-370582
  • Agency: NCRR NIH HHS, Id: M01 RR000064-370591
  • Agency: NCRR NIH HHS, Id: M01 RR000064-37S10579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-37S10582
  • Agency: NCRR NIH HHS, Id: M01 RR000064-37S10591
  • Agency: NCRR NIH HHS, Id: M01 RR000064-380579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-380582
  • Agency: NCRR NIH HHS, Id: M01 RR000064-380591
  • Agency: NCRR NIH HHS, Id: M01 RR000064-390579
  • Agency: NCRR NIH HHS, Id: M01 RR000064-390582
  • Agency: NCRR NIH HHS, Id: M01 RR000064-390591
  • Agency: NCRR NIH HHS, Id: M01-RR00064
  • Agency: NIMH NIH HHS, Id: MH061009
  • Agency: NIMH NIH HHS, Id: MH0666730
  • Agency: NIMH NIH HHS, Id: MH64547
  • Agency: NIMH NIH HHS, Id: MH69359
  • Agency: NINDS NIH HHS, Id: NS049261
  • Agency: NICHD NIH HHS, Id: P01 HD035476-03
  • Agency: NICHD NIH HHS, Id: P01 HD035476-04
  • Agency: NICHD NIH HHS, Id: P01 HD035476-04S1
  • Agency: NICHD NIH HHS, Id: P01 HD035476-04S2
  • Agency: NICHD NIH HHS, Id: P01 HD035476-05
  • Agency: NICHD NIH HHS, Id: P50 HD055751
  • Agency: NICHD NIH HHS, Id: P50 HD055751-01
  • Agency: NICHD NIH HHS, Id: P50 HD055751-010002
  • Agency: NICHD NIH HHS, Id: P50 HD055751-019003
  • Agency: NICHD NIH HHS, Id: P50 HD055751-02
  • Agency: NICHD NIH HHS, Id: P50 HD055751-020002
  • Agency: NICHD NIH HHS, Id: P50 HD055751-03
  • Agency: NICHD NIH HHS, Id: P50 HD055751-030002
  • Agency: NICHD NIH HHS, Id: P50 HD055751-04
  • Agency: NICHD NIH HHS, Id: P50 HD055782-01
  • Agency: NIMH NIH HHS, Id: R01 MH057881
  • Agency: NIMH NIH HHS, Id: R01 MH061009
  • Agency: NIMH NIH HHS, Id: R01 MH061009-01A1
  • Agency: NIMH NIH HHS, Id: R01 MH061009-01A1S1
  • Agency: NIMH NIH HHS, Id: R01 MH061009-02
  • Agency: NIMH NIH HHS, Id: R01 MH061009-03
  • Agency: NIMH NIH HHS, Id: R01 MH061009-04A1
  • Agency: NIMH NIH HHS, Id: R01 MH061009-05
  • Agency: NIMH NIH HHS, Id: R01 MH061009-06
  • Agency: NIMH NIH HHS, Id: R01 MH061009-07
  • Agency: NIMH NIH HHS, Id: R01 MH061009-08
  • Agency: NIMH NIH HHS, Id: R01 MH064547
  • Agency: NIMH NIH HHS, Id: R01 MH064547-01
  • Agency: NIMH NIH HHS, Id: R01 MH064547-01S1
  • Agency: NIMH NIH HHS, Id: R01 MH064547-02
  • Agency: NIMH NIH HHS, Id: R01 MH064547-02S1
  • Agency: NIMH NIH HHS, Id: R01 MH064547-03
  • Agency: NIMH NIH HHS, Id: R01 MH064547-04
  • Agency: NIMH NIH HHS, Id: R01 MH064547-05
  • Agency: NIMH NIH HHS, Id: R01 MH069359
  • Agency: NIMH NIH HHS, Id: R01 MH069359-01A2
  • Agency: NIMH NIH HHS, Id: R01 MH069359-02
  • Agency: NIMH NIH HHS, Id: R01 MH069359-03
  • Agency: NIMH NIH HHS, Id: R01 MH069359-04
  • Agency: NIMH NIH HHS, Id: R01 MH069359-05
  • Agency: NINDS NIH HHS, Id: R01 NS049261
  • Agency: NINDS NIH HHS, Id: R01 NS049261-01A2
  • Agency: NINDS NIH HHS, Id: R01 NS049261-02
  • Agency: NINDS NIH HHS, Id: R01 NS049261-03
  • Agency: NINDS NIH HHS, Id: R01 NS049261-04
  • Agency: NINDS NIH HHS, Id: R01 NS049261-05
  • Agency: NIMH NIH HHS, Id: U10 MH066766-02S1
  • Agency: NIMH NIH HHS, Id: U10MH66766-02S1
  • Agency: NICHD NIH HHS, Id: U19 HD035476-06
  • Agency: NICHD NIH HHS, Id: U19 HD035476-07
  • Agency: NICHD NIH HHS, Id: U19 HD035476-08
  • Agency: NICHD NIH HHS, Id: U19 HD035476-09
  • Agency: NICHD NIH HHS, Id: U19 HD035476-10
  • Agency: NIMH NIH HHS, Id: U24 MH081810
  • Agency: NIMH NIH HHS, Id: U24 MH081810-01
  • Agency: NIMH NIH HHS, Id: U24 MH081810-02
  • Agency: NIMH NIH HHS, Id: U24 MH081810-03
  • Agency: NIMH NIH HHS, Id: U24 MH081810-04
  • Agency: NIMH NIH HHS, Id: U54 MH066673
  • Agency: NIMH NIH HHS, Id: U54 MH066673-01A10001
  • Agency: NIMH NIH HHS, Id: U54 MH066673-020001
  • Agency: NIMH NIH HHS, Id: U54 MH066673-030001
  • Agency: NIMH NIH HHS, Id: U54 MH066673-040001
  • Agency: NIMH NIH HHS, Id: U54 MH066673-05
  • Agency: NIMH NIH HHS, Id: U54 MH066673-050001
  • Agency: NCRR NIH HHS, Id: UL1 RR024134
  • Agency: NCRR NIH HHS, Id: UL1 RR024134-03
  • Agency: NCRR NIH HHS, Id: UL1-RR024134-03
  • Agency: Medical Research Council, Id:

Mesh Terms

  • Autistic Disorder
  • Case-Control Studies
  • Cell Adhesion Molecules, Neuronal
  • Cohort Studies
  • Europe
  • Gene Dosage
  • Gene Regulatory Networks
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome, Human
  • Genotype
  • Humans
  • Neurons
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Reproducibility of Results
  • Ubiquitin