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Detection of clinically relevant exonic copy‐number changes by array CGH
Author(s) -
Boone Philip M.,
Bacino Carlos A.,
Shaw Chad A.,
Eng Patricia A.,
Hixson Patricia M.,
Pursley Amber N.,
Kang SungHae L.,
Yang Yaping,
Wiszniewska Joanna,
Nowakowska Beata A.,
del Gaudio Daniela,
Xia Zhilian,
SimpsonPatel Gayle,
Immken LaDonna L.,
Gibson James B.,
Tsai Anne C.H.,
Bowers Jennifer A.,
Reimschisel Tyler E.,
Schaaf Christian P.,
Potocki Lorraine,
Scaglia Fernando,
Gambin Tomasz,
Sykulski Maciej,
Bartnik Magdalena,
Derwinska Katarzyna,
WisniowieckaKowalnik Barbara,
Lalani Seema R.,
Probst Frank J.,
Bi Weimin,
Beaudet Arthur L.,
Patel Ankita,
Lupski James R.,
Cheung Sau Wai,
Stankiewicz Pawel
Publication year - 2010
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21360
Subject(s) - copy number variation , comparative genomic hybridization , biology , genetics , copy number analysis , exon , phenotype , genome , computational biology , gene , gene dosage , gene duplication , human genome , gene expression
Array comparative genomic hybridization (aCGH) is a powerful tool for the molecular elucidation and diagnosis of disorders resulting from genomic copy‐number variation (CNV). However, intragenic deletions or duplications—those including genomic intervals of a size smaller than a gene—have remained beyond the detection limit of most clinical aCGH analyses. Increasing array probe number improves genomic resolution, although higher cost may limit implementation, and enhanced detection of benign CNV can confound clinical interpretation. We designed an array with exonic coverage of selected disease and candidate genes and used it clinically to identify losses or gains throughout the genome involving at least one exon and as small as several hundred base pairs in size. In some patients, the detected copy‐number change occurs within a gene known to be causative of the observed clinical phenotype, demonstrating the ability of this array to detect clinically relevant CNVs with subkilobase resolution. In summary, we demonstrate the utility of a custom‐designed, exon‐targeted oligonucleotide array to detect intragenic copy‐number changes in patients with various clinical phenotypes. Hum Mutat 31:1–17, 2010. © 2010 Wiley‐Liss, Inc.