Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing
| Autor: | Hans-Georg O. Bock, Carlos A. Bacino, James R. Lupski, Christine M. Eng, Arthur L. Beaudet, Chad A. Shaw, Weimin Bi, Pawel Stankiewicz, Chun-hui Tsai, Frank J. Probst, Amber N. Pursley, Seema R. Lalani, Sau Wai Cheung, Joanna Wiszniewska, Patricia Hixson, Ankita Patel, Tomasz Gambin, Sung-Hae L. Kang, Maria Descartes, Fernando Scaglia |
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| Rok vydání: | 2012 |
| Předmět: |
Heterozygote
DNA Copy Number Variations Genotyping Techniques uniparental disomy medically actionable variants Copy number analysis SNP Biology Molecular Inversion Probe Polymorphism Single Nucleotide Article absence of heterozygosity Genetics Humans array CGH Genetics (clinical) Oligonucleotide Array Sequence Analysis Comparative Genomic Hybridization Genome Human Genomics Tag SNP SNP genotyping Virtual karyotype SNP array Comparative genomic hybridization |
| Zdroj: | European Journal of Human Genetics |
| ISSN: | 1476-5438 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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