Detection of clinically relevant exonic copy-number changes by array CGH.
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.
Boone
Philip M
PM
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Bacino
Carlos A
CA
Shaw
Chad A
CA
Eng
Patricia A
PA
Hixson
Patricia M
PM
Pursley
Amber N
AN
Kang
Sung-Hae L
SH
Yang
Yaping
Y
Wiszniewska
Joanna
J
Nowakowska
Beata A
BA
del Gaudio
Daniela
D
Xia
Zhilian
Z
Simpson-Patel
Gayle
G
Immken
LaDonna L
LL
Gibson
James B
JB
Tsai
Anne C-H
AC
Bowers
Jennifer A
JA
Reimschisel
Tyler E
TE
Schaaf
Christian P
CP
Potocki
Lorraine
L
Scaglia
Fernando
F
Gambin
Tomasz
T
Sykulski
Maciej
M
Bartnik
Magdalena
M
Derwinska
Katarzyna
K
Wisniowiecka-Kowalnik
Barbara
B
Lalani
Seema R
SR
Probst
Frank J
FJ
Bi
Weimin
W
Beaudet
Arthur L
AL
Patel
Ankita
A
Lupski
James R
JR
Cheung
Sau Wai
SW
Stankiewicz
Pawel
P
D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D056905:Chromosome Breakpoints; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D055815:Young Adult