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

Joseph T. Glessner, Kai Wang, Guiqing Cai, Olena Korvatska, Cecilia E. Kim, Shawn Wood, Haitao Zhang, Annette Estes, Camille W. Brune, Jonathan P. Bradfield, Marcin Imielinski, Edward C. Frackelton, Jennifer Reichert, Emily L. Crawford, Jeffrey Munson, Patrick M A Sleiman, Rosetta Chiavacci, Kiran Annaiah, Kelly Thomas, Cuiping HouWendy Glaberson, James Flory, Frederick Otieno, Maria Garris, Latha Soorya, Lambertus Klei, Joseph Piven, Kacie J. Meyer, Evdokia Anagnostou, Takeshi Sakurai, Rachel M. Game, Danielle S. Rudd, Danielle Zurawiecki, Christopher J. McDougle, Lea K. Davis, Judith Miller, David J. Posey, Shana Michaels, Alexander Kolevzon, Jeremy M. Silverman, Raphael Bernier, Susan E. Levy, Robert T. Schultz, Geraldine Dawson, Thomas Owley, William M. McMahon, Thomas H. Wassink, John A. Sweeney, John Nurnberger, Hilary Coon, James S. Sutcliffe, Nancy J. Minshew, Struan F A Grant, Maja Bucan, Edwin H. Cook, Joseph D. Buxbaum, Bernie Devlin, Gerard D. Schellenberg, Hakon Hakonarson

Research output: Contribution to journalArticle

886 Citations (Scopus)

Abstract

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 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 × 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 × 10-3). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 × 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.

Original languageEnglish
Pages (from-to)569-572
Number of pages4
JournalNature
Volume459
Issue number7246
DOIs
StatePublished - May 28 2009

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Autistic Disorder
Ubiquitin
Genome
Genes
Neuronal Cell Adhesion Molecules
Autism Spectrum Disorder
Gene Regulatory Networks
Genetic Predisposition to Disease
Cell Adhesion
Single Nucleotide Polymorphism
Central Nervous System
Complementary DNA

ASJC Scopus subject areas

  • General

Cite this

Glessner, J. T., Wang, K., Cai, G., Korvatska, O., Kim, C. E., Wood, S., ... Hakonarson, H. (2009). Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature, 459(7246), 569-572. https://doi.org/10.1038/nature07953

Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. / Glessner, Joseph T.; Wang, Kai; Cai, Guiqing; Korvatska, Olena; Kim, Cecilia E.; Wood, Shawn; Zhang, Haitao; Estes, Annette; Brune, Camille W.; Bradfield, Jonathan P.; Imielinski, Marcin; Frackelton, Edward C.; Reichert, Jennifer; Crawford, Emily L.; Munson, Jeffrey; Sleiman, Patrick M A; Chiavacci, Rosetta; Annaiah, Kiran; Thomas, Kelly; Hou, Cuiping; Glaberson, Wendy; Flory, James; Otieno, Frederick; Garris, Maria; Soorya, Latha; Klei, Lambertus; Piven, Joseph; Meyer, Kacie J.; Anagnostou, Evdokia; Sakurai, Takeshi; Game, Rachel M.; Rudd, Danielle S.; Zurawiecki, Danielle; McDougle, Christopher J.; Davis, Lea K.; Miller, Judith; Posey, David J.; Michaels, Shana; Kolevzon, Alexander; Silverman, Jeremy M.; Bernier, Raphael; Levy, Susan E.; Schultz, Robert T.; Dawson, Geraldine; Owley, Thomas; McMahon, William M.; Wassink, Thomas H.; Sweeney, John A.; Nurnberger, John; Coon, Hilary; Sutcliffe, James S.; Minshew, Nancy J.; Grant, Struan F A; Bucan, Maja; Cook, Edwin H.; Buxbaum, Joseph D.; Devlin, Bernie; Schellenberg, Gerard D.; Hakonarson, Hakon.

In: Nature, Vol. 459, No. 7246, 28.05.2009, p. 569-572.

Research output: Contribution to journalArticle

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, PMA, 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, J, Coon, H, Sutcliffe, JS, Minshew, NJ, Grant, SFA, Bucan, M, Cook, EH, Buxbaum, JD, Devlin, B, Schellenberg, GD & Hakonarson, H 2009, 'Autism genome-wide copy number variation reveals ubiquitin and neuronal genes', Nature, vol. 459, no. 7246, pp. 569-572. https://doi.org/10.1038/nature07953
Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009 May 28;459(7246):569-572. https://doi.org/10.1038/nature07953
Glessner, Joseph T. ; Wang, Kai ; Cai, Guiqing ; Korvatska, Olena ; Kim, Cecilia E. ; Wood, Shawn ; Zhang, Haitao ; Estes, Annette ; Brune, Camille W. ; Bradfield, Jonathan P. ; Imielinski, Marcin ; Frackelton, Edward C. ; Reichert, Jennifer ; Crawford, Emily L. ; Munson, Jeffrey ; Sleiman, Patrick M A ; Chiavacci, Rosetta ; Annaiah, Kiran ; Thomas, Kelly ; Hou, Cuiping ; Glaberson, Wendy ; Flory, James ; Otieno, Frederick ; Garris, Maria ; Soorya, Latha ; Klei, Lambertus ; Piven, Joseph ; Meyer, Kacie J. ; Anagnostou, Evdokia ; Sakurai, Takeshi ; Game, Rachel M. ; Rudd, Danielle S. ; Zurawiecki, Danielle ; McDougle, Christopher J. ; Davis, Lea K. ; Miller, Judith ; Posey, David J. ; Michaels, Shana ; Kolevzon, Alexander ; Silverman, Jeremy M. ; Bernier, Raphael ; Levy, Susan E. ; Schultz, Robert T. ; Dawson, Geraldine ; Owley, Thomas ; McMahon, William M. ; Wassink, Thomas H. ; Sweeney, John A. ; Nurnberger, John ; Coon, Hilary ; Sutcliffe, James S. ; Minshew, Nancy J. ; Grant, Struan F A ; Bucan, Maja ; Cook, Edwin H. ; Buxbaum, Joseph D. ; Devlin, Bernie ; Schellenberg, Gerard D. ; Hakonarson, Hakon. / Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. In: Nature. 2009 ; Vol. 459, No. 7246. pp. 569-572.
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AU - Wood, Shawn

AU - Zhang, Haitao

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AU - Sutcliffe, James S.

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