Skip Navigation



Human Molecular Genetics Advance Access published online on December 21, 2007
Human Molecular Genetics, doi:10.1093/hmg/ddm376
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrowOA All Versions of this Article:
17/4/628    most recent
ddm376v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Kumar, R. A.
Right arrow Articles by Christian, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kumar, R. A.
Right arrow Articles by Christian, S. L.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Recurrent 16p11.2 microdeletions in autism

Ravinesh A. Kumar1, Samer KaraMohamed1, Jyotsna Sudi1, Donald F. Conrad1, Camille Brune5, Judith A. Badner4, T. Conrad Gilliam1, Norma J. Nowak6, Edwin H. Cook, Jr.5, William B. Dobyns1,2,3 and Susan L. Christian1,*

1 Departments of Human Genetics, University of Chicago, Chicago, IL 60637, USA 2 Departments of Neurology, University of Chicago, Chicago, IL 60637, USA 3 Departments of Pediatrics, University of Chicago, Chicago, IL 60637, USA 4 Departments of Psychiatry, University of Chicago, Chicago, IL 60637, USA 5 Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA 6 Roswell Park Cancer Institute, Department of Cancer Genetics; Buffalo, NY 14236, USA.

* Corresponding author: Susan L. Christian, Ph.D., Department of Human Genetics, University of Chicago, 920 East 58th Street, CLSC 319, Chicago, IL 60637, Phone: 773-834-2971, Fax: 773-834-8470, Email: schrist{at}bsd.uchicago.edu

Received November 21, 2007; Revised December 19, 2007; Accepted December 19, 2007

Autism is a childhood neurodevelopmental disorder with a strong genetic component, yet the identification of autism susceptibility loci remains elusive. We investigated 180 autism probands and 372 control subjects by array comparative genomic hybridization (aCGH) using a 19K whole genome tiling path bacterial artificial chromosome (BAC) microarray to identify submicroscopic chromosomal rearrangements specific to autism. We discovered a recurrent 16p11.2 microdeletion in 2 probands with autism and none in controls. The deletion spans ~500-kb and is flanked by ~147-kb segmental duplications (SDs) that are>99% identical, a common characteristic of genomic disorders. We assessed the frequency of this new autism genomic disorder by screening an additional 532 probands and 465 controls by quantitative PCR and identified 2 more patients but no controls with the microdeletion, indicating a combined frequency of 0.6% (4/712 autism versus 0/837 controls; Fisher exact test p-value = 0.044). We confirmed all 16p11.2 deletions using FISH, microsatellite analyses and aCGH, and mapped the approximate deletion breakpoints to the edges of the flanking SDs using a custom-designed high density oligonucleotide microarray. Bioinformatic analysis localized 12 of the 25 genes within the microdeletion to nodes in one interaction network. We performed phenotype analyses and found no striking features that distinguish patients with the 16p11.2 microdeletion as a distinct autism subtype. Our work reports the first frequency, breakpoint, bioinformatic and phenotypic analyses of a de novo 16p11.2 microdeletion that represents one of the most common recurrent genomic disorders associated with autism to date.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 BrainHome page
C. G. F. de Kovel, H. Trucks, I. Helbig, H. C. Mefford, C. Baker, C. Leu, C. Kluck, H. Muhle, S. von Spiczak, P. Ostertag, et al.
Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies
Brain, October 20, 2009; (2009) awp262v1.
[Abstract] [Full Text] [PDF]

Home page
 Arch Gen PsychiatryHome page
A. Guilmatre, C. Dubourg, A.-L. Mosca, S. Legallic, A. Goldenberg, V. Drouin-Garraud, V. Layet, A. Rosier, S. Briault, F. Bonnet-Brilhault, et al.
Recurrent Rearrangements in Synaptic and Neurodevelopmental Genes and Shared Biologic Pathways in Schizophrenia, Autism, and Mental Retardation
Arch Gen Psychiatry, September 1, 2009; 66(9): 947 - 956.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
H. C. Mefford, G. M. Cooper, T. Zerr, J. D. Smith, C. Baker, N. Shafer, E. C. Thorland, C. Skinner, C. E. Schwartz, D. A. Nickerson, et al.
A method for rapid, targeted CNV genotyping identifies rare variants associated with neurocognitive disease
Genome Res., September 1, 2009; 19(9): 1579 - 1585.
[Abstract] [Full Text] [PDF]

Home page
 Cold Spring Harb Symp Quant BiolHome page
T. Marques-Bonet and E.E. Eichler
The Evolution of Human Segmental Duplications and the Core Duplicon Hypothesis
Cold Spring Harb Symp Quant Biol, August 28, 2009; (2009) sqb.2009.74.011v1.
[Abstract] [PDF]

Home page
 Hum Mol GenetHome page
M. K. Rudd, J. Keene, B. Bunke, E. B. Kaminsky, M. P. Adam, J. G. Mulle, D. H. Ledbetter, and C. L. Martin
Segmental duplications mediate novel, clinically relevant chromosome rearrangements
Hum. Mol. Genet., August 15, 2009; 18(16): 2957 - 2962.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Kilpinen, T. Ylisaukko-oja, K. Rehnstrom, E. Gaal, J. A. Turunen, E. Kempas, L. von Wendt, T. Varilo, and L. Peltonen
Linkage and linkage disequilibrium scan for autism loci in an extended pedigree from Finland
Hum. Mol. Genet., August 1, 2009; 18(15): 2912 - 2921.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
Psychiatric GWAS Consortium Coordinating Committee
Genomewide Association Studies: History, Rationale, and Prospects for Psychiatric Disorders
Am J Psychiatry, May 1, 2009; 166(5): 540 - 556.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
E. D. Salman, S. A. Kadlubar, and C. N. Falany
Expression and Localization of Cytosolic Sulfotransferase (SULT) 1A1 and SULT1A3 in Normal Human Brain
Drug Metab. Dispos., April 1, 2009; 37(4): 706 - 709.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
Y. Shen and B.-L. Wu
Microarray-Based Genomic DNA Profiling Technologies in Clinical Molecular Diagnostics
Clin. Chem., April 1, 2009; 55(4): 659 - 669.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
D T Miller, Y Shen, L A Weiss, J Korn, I Anselm, C Bridgemohan, G F Cox, H Dickinson, J Gentile, D J Harris, et al.
Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders
J. Med. Genet., April 1, 2009; 46(4): 242 - 248.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
A. Gusev, J. K. Lowe, M. Stoffel, M. J. Daly, D. Altshuler, J. L. Breslow, J. M. Friedman, and I. Pe'er
Whole population, genome-wide mapping of hidden relatedness
Genome Res., February 1, 2009; 19(2): 318 - 326.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
D L Bruno, D Ganesamoorthy, J Schoumans, A Bankier, D Coman, M Delatycki, R J M Gardner, M Hunter, P A James, P Kannu, et al.
Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice
J. Med. Genet., February 1, 2009; 46(2): 123 - 131.
[Abstract] [Full Text] [PDF]

Home page
 Schizophr BullHome page
D. St Clair
Copy Number Variation and Schizophrenia
Schizophr Bull, January 1, 2009; 35(1): 9 - 12.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
C Lintas and A M Persico
Autistic phenotypes and genetic testing: state-of-the-art for the clinical geneticist
J. Med. Genet., January 1, 2009; 46(1): 1 - 8.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
J Rochette, P Roll, and P Szepetowski
Genetics of infantile seizures with paroxysmal dyskinesia: the infantile convulsions and choreoathetosis (ICCA) and ICCA-related syndromes
J. Med. Genet., December 1, 2008; 45(12): 773 - 779.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
E. M. Morrow, S.-Y. Yoo, S. W. Flavell, T.-K. Kim, Y. Lin, R. S. Hill, N. M. Mukaddes, S. Balkhy, G. Gascon, A. Hashmi, et al.
Identifying Autism Loci and Genes by Tracing Recent Shared Ancestry
Science, July 11, 2008; 321(5886): 218 - 223.
[Abstract] [Full Text] [PDF]

Home page
 JWatch NeurologyHome page
Genetics of Autism: Escalating Complexities
Journal Watch Neurology, April 1, 2008; 2008(401): 2 - 2.
[Full Text]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.