Exome Sequencing vs RNA-Seq to Identify Coding Region Variants

Whole Genome Sequencing

The advent of next-generation sequencing technologies has revolutionized the study of genetic variation in the human genome. Whole-genome sequencing currently represents the most comprehensive strategy for variant detection genome-wide but is costly for large sample sizes, and variants detected in noncoding regions remain largely uninterpretable.

Whole Exome Sequencing

By contrast, whole-exome sequencing has been widely applied in the identification of germline mutations underlying Mendelian disorders, somatic mutations in various cancers and de novo mutations in neurodevelopmental disorders. Since whole-exome sequencing focuses upon the entire set of exons in the genome (the exome), it requires additional exome-enrichment steps compared with whole-genome sequencing. Although the availability of multiple commercial exome-enrichment kits has made whole-exome sequencing technically feasible, it has also added to the overall cost.

Transcriptome Sequencing

This has led to the emergence of transcriptome (or RNA) sequencing as a potential alternative approach to variant detection within protein coding regions, since the transcriptome of a given tissue represents a quasi-complete set of transcribed genes (mRNAs) and other noncoding RNAs. A further advantage of this approach is that it bypasses the need for exome enrichment.

  • Ku CS, Wu M, Cooper DN, Naidoo N, Pawitan Y, Pang B, Iacopetta B, Soong R. (2012) Exome versus transcriptome sequencing in identifying coding region variants. Expert Rev Mol Diagn 12(3), 241-51. [abstract]