title: Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing.
abstract: In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, and neuropsychiatric disorders. Differences in the ability to resolve genomic changes between these arrays may constitute an implementation challenge for clinicians: which platform (SNP vs array CGH) might best detect the underlying genetic cause for the disease in the patient? While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect single-exon copy number variants (CNVs) due to the distribution of SNPs across the genome. To provide comprehensive clinical testing for both CNVs and copy-neutral AOH, we enhanced our custom-designed high-resolution oligonucleotide array that has exon-targeted coverage of 1860 genes with 60,000 SNP probes, referred to as Chromosomal Microarray Analysis - Comprehensive (CMA-COMP). Of the 3240 cases evaluated by this array, clinically significant CNVs were detected in 445 cases including 21 cases with exonic events. In addition, 162 cases (5.0%) showed at least one AOH region >10 Mb. We demonstrate that even though this array has a lower density of SNP probes than other commercially available SNP arrays, it reliably detected AOH events >10 Mb as well as exonic CNVs beyond the detection limitations of SNP genotyping. Thus, combining SNP probes and exon-targeted array CGH into one platform provides clinically useful genetic screening in an efficient manner.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wiszniewska
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Shaw
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.affiliation: Allina Cytogenetics Laboratory, Abbott Northwestern Hospital, Minneapolis, MN, USA.
authors.forename: Sung-Hae L
authors.initials: SH
authors.lastname: Kang
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Amber N
authors.initials: AN
authors.lastname: Pursley
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Lalani
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Hixson
authors.affiliation: Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.affiliation: 1] Department of Molecular and Medical Genetics, Oregon Health and Sciences University-OHSU, Portland, OR, USA [2] Department of Pediatrics, The Children's Hospital, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: Chun-hui
authors.initials: CH
authors.lastname: Tsai
authors.affiliation: Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Bock
authors.affiliation: Department of Genetics, University of Alabama, Birmingham, AL, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Descartes
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Probst
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Eng
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.affiliation: 1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA [2] Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bacino
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
mesh_terms: D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations / Q000235:genetics*; D015894:Genome, Human; D023281:Genomics; D060005:Genotyping Techniques / Q000379:methods*; D006579:Heterozygote; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*