title: Technological advances in DNA sequence enrichment and sequencing for germline genetic diagnosis.
abstract: The potential applications of next-generation sequencing technologies in diagnostic laboratories have become increasingly evident despite the various technical challenges that still need to be overcome to potentiate its widespread adoption in a clinical setting. Whole-genome sequencing is now both technically feasible and 'cost effective' using next-generation sequencing techniques. However, this approach is still considered to be 'expensive' for a diagnostic test. Although the goal of the US$1000 genome is fast approaching, neither the analytical hurdles nor the ethical issues involved are trivial. In addition, the cost of data analysis and storage has been much higher than initially expected. As a result, it is widely perceived that targeted sequencing and whole-exome sequencing are more likely to be adopted as diagnostic tools in the foreseeable future. However, the information-generating power of whole-exome sequencing has also sparked considerable debate in relation to its deployment in genetic diagnostics, particularly with reference to the revelation of incidental findings. In this review, we focus on the targeted sequencing approach and its potential as a genetic diagnostic tool.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, 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: D059472:Exome; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D060885:Multiplex Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*