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.

Keywords::

• diagnostic
• exome
• Mendelian disorder
• next-generation sequencing
• sequence enrichment

Acknowledgements

C-S Ku, M Wu, DN Cooper and R Soong contributed to the conceptualization of this article. C-S Ku, M Wu and DN Cooper contributed to the writing of the article and the preparation of the table. N Naidoo, Y Pawitan, B Pang and B Iacopetta were involved in the discussion and critical reading. C-S Ku, M Wu and R Soong approved the final version and had final responsibility for this article.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.