Copy Number Variant Detection with Low-Coverage Whole-Genome Sequencing Represents a Viable Alternative to the Conventional Array-CGH

被引:4
|
作者
Kucharik, Marcel [1 ,2 ]
Budis, Jaroslav [1 ,2 ,3 ]
Hyblova, Michaela [4 ]
Minarik, Gabriel [4 ]
Szemes, Tomas [1 ,2 ,5 ]
机构
[1] Geneton Sro, Bratislava 84104, Slovakia
[2] Comenius Univ Sci Pk, Bratislava 84104, Slovakia
[3] Slovak Ctr Sci & Tech Informat, Bratislava 81104, Slovakia
[4] Trisomy Test Sro, Bratislava 84104, Slovakia
[5] Comenius Univ, Fac Nat Sci, Dept Mol Biol, Bratislava 84215, Slovakia
关键词
CNV detection; low-coverage WGS; CNV detection comparison; aCGH replacement;
D O I
10.3390/diagnostics11040708
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Copy number variations (CNVs) represent a type of structural variant involving alterations in the number of copies of specific regions of DNA that can either be deleted or duplicated. CNVs contribute substantially to normal population variability, however, abnormal CNVs cause numerous genetic disorders. At present, several methods for CNV detection are applied, ranging from the conventional cytogenetic analysis, through microarray-based methods (aCGH), to next-generation sequencing (NGS). In this paper, we present GenomeScreen, an NGS-based CNV detection method for low-coverage, whole-genome sequencing. We determined the theoretical limits of its accuracy and obtained confirmation in an extensive in silico study and in real patient samples with known genotypes. In theory, at least 6 M uniquely mapped reads are required to detect a CNV with the length of 100 kilobases (kb) or more with high confidence (Z-score > 7). In practice, the in silico analysis required at least 8 M to obtain >99% accuracy (for 100 kb deviations). We compared GenomeScreen with one of the currently used aCGH methods in diagnostic laboratories, which has mean resolution of 200 kb. GenomeScreen and aCGH both detected 59 deviations, while GenomeScreen furthermore detected 134 other (usually) smaller variations. When compared to aCGH, overall performance of the proposed GenemoScreen tool is comparable or superior in terms of accuracy, turn-around time, and cost-effectiveness, thus providing reasonable benefits, particularly in a prenatal diagnosis setting.
引用
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页数:11
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