Copyright © 2006 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 79, Issue 3, 500-513, 1 September 2006
doi:10.1086/507471
Article
Oligonucleotide Microarray Analysis of Genomic Imbalance in Children with Mental Retardation
J.M. Friedmana, b, 
, 
, Ágnes Barossd, Allen D. Delaneyd, Adrian Allyd, Laura Arbourb, Jennifer Asanod, Dione K. Baileye, Sarah Barberd, Patricia Bircha, Mabel Brown-Johnd, Manqiu Caoe, Susanna Chand, David L. Charestd, Noushin Farnoudd, Nicole Fernandesa, Stephane Flibotted, Anne God, William T. Gibsonb, Robert A. Holtd, Steven J.M. Jonesd, Giulia C. Kennedye, Martin Krzywinskid, Sylvie Langloisa, b, Haiyan I. Lid, Barbara C. McGillivraya, b, Tarun Nayard, Trevor J. Pughd, Evica Rajcan-Separovicc, Jacqueline E. Scheind, Angelique Schnerchd, Asim Siddiquid, Margot I. Van Allenb, Gary Wilsond, Siu-Li Yongb, Farah Zahira, Patrice Eydouxc and Marco A. Marraa, d
a Department of Medical Genetics, University of British Columbia, Vancouver
b Provincial Medical Genetics Program, Vancouver
c Department of Pathology and Laboratory Medicine, Vancouver
d Children's & Women's Hospital, and Genome Sciences Centre, British Columbia Cancer Agency, Vancouver
e Affymetrix, Santa Clara, CA
Address for correspondence and reprints: Dr. J. M. Friedman, Medical Genetics Research Unit, Children's & Women's Hospital, 4500 Oak Street, Box 153, Vancouver, British Columbia, Canada V6H 3N1Abstract
The cause of mental retardation in one-third to one-half of all affected individuals is unknown. Microscopically detectable chromosomal abnormalities are the most frequently recognized cause, but gain or loss of chromosomal segments that are too small to be seen by conventional cytogenetic analysis has been found to be another important cause. Array-based methods offer a practical means of performing a high-resolution survey of the entire genome for submicroscopic copy-number variants. We studied 100 children with idiopathic mental retardation and normal results of standard chromosomal analysis, by use of whole-genome sampling analysis with Affymetrix GeneChip Human Mapping 100K arrays. We found de novo deletions as small as 178 kb in eight cases, de novo duplications as small as 1.1 Mb in two cases, and unsuspected mosaic trisomy 9 in another case. This technology can detect at least twice as many potentially pathogenic de novo copy-number variants as conventional cytogenetic analysis can in people with mental retardation.
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