Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing

Joanna Wiszniewska , Weimin Bi , Chad Shaw , Pawel Stankiewicz , Sung-Hae L. Kang , Amber N. Pursley , Seema Lalani , Patricia Hixson , Tomasz Gambin , Chun-Hui Tsai , Hans-Georg Bock , Maria Descartes , Frank J. Probst , Fernando Scaglia , Arthur L. Beaudet , James R. Lupski , Christine Eng , Sau Wai Cheung , Carlos Bacino , Ankita Patel


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.
Author Joanna Wiszniewska - [Baylor College of Medicine]
Joanna Wiszniewska,,
, Weimin Bi - [Baylor College of Medicine]
Weimin Bi,,
, Chad Shaw - [Baylor College of Medicine]
Chad Shaw,,
, Pawel Stankiewicz - [Baylor College of Medicine]
Pawel Stankiewicz,,
, Sung-Hae L. Kang
Sung-Hae L. Kang,,
, Amber N. Pursley
Amber N. Pursley,,
, Seema Lalani - [Baylor College of Medicine]
Seema Lalani,,
, Patricia Hixson - [Baylor College of Medicine]
Patricia Hixson,,
, Tomasz Gambin (FEIT / IN)
Tomasz Gambin,,
- The Institute of Computer Science
, Chun-Hui Tsai - [Oregon Health and Science University]
Chun-Hui Tsai,,
et al.`
Journal seriesEuropean Journal of Human Genetics, ISSN 1018-4813
Issue year2013
Publication size in sheets0.5
Keywords in Englisharray CGH; SNP; uniparental disomy; absence of heterozygosity; medically actionable variants
ASJC Classification2716 Genetics(clinical); 1311 Genetics
Languageen angielski
Score (nominal)35
Score sourcejournalList
ScoreMinisterial score = 35.0, 15-05-2020, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 15-05-2020, ArticleFromJournal
Publication indicators WoS Citations = 66; Scopus Citations = 71; GS Citations = 13.0; Scopus SNIP (Source Normalised Impact per Paper): 2013 = 1.263; WoS Impact Factor: 2013 = 4.225 (2) - 2013=3.943 (5)
Citation count*13 (2015-01-25)
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