作者
Andrew M Gross, Subramanian S Ajay, Vani Rajan, Carolyn Brown, Krista Bluske, Nicole J Burns, Aditi Chawla, Alison J Coffey, Alka Malhotra, Alicia Scocchia, Erin Thorpe, Natasa Dzidic, Karine Hovanes, Trilochan Sahoo, Egor Dolzhenko, Bryan Lajoie, Amirah Khouzam, Shimul Chowdhury, John Belmont, Eric Roller, Sergii Ivakhno, Stephen Tanner, Julia McEachern, Tina Hambuch, Michael Eberle, R Tanner Hagelstrom, David R Bentley, Denise L Perry, Ryan J Taft
发表日期
2019/5/1
期刊
Genetics in Medicine
卷号
21
期号
5
页码范围
1121-1130
出版商
Elsevier
简介
Purpose
Current diagnostic testing for genetic disorders involves serial use of specialized assays spanning multiple technologies. In principle, genome sequencing (GS) can detect all genomic pathogenic variant types on a single platform. Here we evaluate copy-number variant (CNV) calling as part of a clinically accredited GS test.
Methods
We performed analytical validation of CNV calling on 17 reference samples, compared the sensitivity of GS-based variants with those from a clinical microarray, and set a bound on precision using orthogonal technologies. We developed a protocol for family-based analysis of GS-based CNV calls, and deployed this across a clinical cohort of 79 rare and undiagnosed cases.
Results
We found that CNV calls from GS are at least as sensitive as those from microarrays, while only creating a modest increase in the number of variants interpreted (~10 CNVs per case). We identified …
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AM Gross, SS Ajay, V Rajan, C Brown, K Bluske… - Genetics in Medicine, 2019