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

3 Jun , 2013 News from the world

European Journal of Human Genetics advance online publication 22 May 2013

Joanna Wiszniewska1, Weimin Bi1, Chad Shaw1, Pawel Stankiewicz1, Sung-Hae L Kang2, Amber N Pursley1, Seema Lalani1,3, Patricia Hixson1, Tomasz Gambin4, Chun-hui Tsai5,6, Hans-Georg Bock7, Maria Descartes8, Frank J Probst1,3, Fernando Scaglia1, Arthur L Beaudet1,3, James R Lupski1,3, Christine Eng1,3, Sau Wai Cheung1,3, Carlos Bacino1,3 and Ankita Patel1

  1. 1Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA
  2. 2Allina Cytogenetics Laboratory, Abbott Northwestern Hospital, Minneapolis, MN, USA
  3. 3Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
  4. 4Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland
  5. 5Department of Molecular and Medical Genetics, Oregon Health and Sciences University—OHSU, Portland, OR, USA
  6. 6Department of Pediatrics, The Children’s Hospital, University of Colorado School of Medicine, Aurora, CO, USA
  7. 7Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA
  8. 8Department of Genetics, University of Alabama, Birmingham, AL, USA


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.

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