title: Exome versus transcriptome sequencing in identifying coding region variants.
abstract: 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. 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. 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. Here we discuss the relative merits and limitations of these approaches as they are applied in the context of variant detection within gene coding regions.
authors.affiliation: Cancer Science Institute of Singapore, #12-01, MD6, Centre for Translational Medicine, NUS Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, 117599, Singapore. g0700040@nus.edu.sg
authors.forename: Chee-Seng
authors.initials: CS
authors.lastname: Ku
authors.forename: Mengchu
authors.initials: M
authors.lastname: Wu
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Nasheen
authors.initials: N
authors.lastname: Naidoo
authors.forename: Yudi
authors.initials: Y
authors.lastname: Pawitan
authors.forename: Brendan
authors.initials: B
authors.lastname: Pang
authors.forename: Barry
authors.initials: B
authors.lastname: Iacopetta
authors.forename: Richie
authors.initials: R
authors.lastname: Soong
mesh_terms: D001483:Base Sequence; D059472:Exome / Q000235:genetics*; D014644:Genetic Variation; D015894:Genome, Human; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D059467:Transcriptome / Q000235:genetics*
chemical_list: D012333:RNA, Messenger