Improved molecular diagnosis by the detection of exonic deletions with target gene capture and deep sequencing

Genet Med. 2015 Feb;17(2):99-107. doi: 10.1038/gim.2014.80. Epub 2014 Jul 17.


Purpose: We aimed to demonstrate the detection of exonic deletions using target capture and deep sequencing data.

Methods: Sequence data from target gene capture followed by massively parallel sequencing were analyzed for the detection of exonic deletions using the normalized mean coverage of individual exons. We compared the results with those obtained from high-density exon-targeted array comparative genomic hybridization and applied similar analysis to examine samples from patients with pathogenic exonic deletions.

Results: Thirty-eight samples, each containing 2,134, 2,833, or 4,688 coding exons from different panels, with a total of 103,863 exons, were analyzed by capture-massively parallel sequencing and array comparative genomic hybridization. Ten deletions detected by array comparative genomic hybridization were all detected by massively parallel sequencing, whereas only two of three duplications were detected. We were able to detect all pathogenic exonic deletions in 11 positive cases. Thirty-one exonic copy number changes from nine perspective clinical samples were also identified.

Conclusion: Our results demonstrated the feasibility of using the same set of sequence data to detect both point mutations and exonic deletions, thus improving the diagnostic power of massively parallel sequencing-based assays.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Comparative Genomic Hybridization
  • DNA Copy Number Variations
  • Exome
  • Exons*
  • Female
  • Genes, Recessive
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics
  • Genetic Testing* / methods
  • Genotype
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • INDEL Mutation
  • Male
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sequence Deletion*