title: Detection of clinically relevant exonic copy-number changes by array CGH.
abstract: 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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Boone
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Eng
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Hixson
authors.forename: Amber N
authors.initials: AN
authors.lastname: Pursley
authors.forename: Sung-Hae L
authors.initials: SH
authors.lastname: Kang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Yang
authors.forename: Joanna
authors.initials: J
authors.lastname: Wiszniewska
authors.forename: Beata A
authors.initials: BA
authors.lastname: Nowakowska
authors.forename: Daniela
authors.initials: D
authors.lastname: del Gaudio
authors.forename: Zhilian
authors.initials: Z
authors.lastname: Xia
authors.forename: Gayle
authors.initials: G
authors.lastname: Simpson-Patel
authors.forename: LaDonna L
authors.initials: LL
authors.lastname: Immken
authors.forename: James B
authors.initials: JB
authors.lastname: Gibson
authors.forename: Anne C-H
authors.initials: AC
authors.lastname: Tsai
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bowers
authors.forename: Tyler E
authors.initials: TE
authors.lastname: Reimschisel
authors.forename: Christian P
authors.initials: CP
authors.lastname: Schaaf
authors.forename: Lorraine
authors.initials: L
authors.lastname: Potocki
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.forename: Maciej
authors.initials: M
authors.lastname: Sykulski
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bartnik
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Derwinska
authors.forename: Barbara
authors.initials: B
authors.lastname: Wisniowiecka-Kowalnik
authors.forename: Seema R
authors.initials: SR
authors.lastname: Lalani
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Probst
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
mesh_terms: 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