Combinatorial approach to estimate copy number genotype using whole-exome sequencing data

• CNV genotype estimation approach using a combination of existing methods
• Our approach was comprehensively compared with the customized Agilent array–comparative genomic hybridization.
• We found that our genotyping approach proved to be accurate, and reproducible, suggesting that it can complement existing CNV genotyping methods.

Copy number variations (CNVs) are known risk factors in complex diseases. Array-based approaches have been widely used to detect CNVs, but limitations of array-based CNV detection methods, such as noisy signal and low resolution, have hindered detection of small CNVs.Recently, the development of next-generation sequencing techniques has increased rapidly owing to declines in cost. Particularly, whole-exome sequencing has proved useful for finding causal genes and variants in complex diseases. Because gene copy number may affect expression, CNV genotyping can be very valuable in disease association studies. However, almost all current CNV detection tools consider only two types of CNV genotypes.In this study, we propose a CNV genotype estimation approach using a combination of existing methods. Our approach was comprehensively compared with the customized Agilent array–comparative genomic hybridization. We found that our genotyping approach proved to be accurate, and reproducible, suggesting that it can complement existing CNV genotyping methods.