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‘Next Generation Sequencing’ as a diagnostic tool in paediatrics
  1. Diana Baralle1,
  2. Vardha Ismail2
  1. 1 Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
  2. 2 Clinical Genetics, Southampton University Hospitals NHS Trust, Southampton, UK
  1. Correspondence to Professor Diana Baralle, Southampton Medicine, University of Southampton, Southampton SO16 6YD, UK; D.Baralle{at}

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Two recent studies in Asia illustrate the potential of next generation sequencing (NGS) and the value of large-scale studies in Asian cohorts to represent variation in the reference genome. The UK itself has a diverse population and acknowledging the genetic variation that exists within differing ethnic groups is important to deliver a high-quality genomic service for all. The paper from Wei et al 1 demonstrates that an understanding of what each NGS test provides allowed for the use of a large exome gene panel rather than whole exome sequencing (WES). This still increased the diagnostic yield to almost 40% in Mendelian disorders. Bhatia et al 2 further showed that using whole exome and whole genome sequencing (WGS) led to a diagnostic yield of 38% and 33%, respectively, in their Asian cohort. Particularly in children with neuromuscular and skeletal dysplasia phenotypes, performing a ‘trio exome’ also contributed to a higher diagnostic yield. Bhatia et al additionally demonstrate that 61% of the variants found in their multiethnic Asian population were novel. This information is crucial to help collate accurate reference data sets, which tend to have a European bias, with Asian ancestry represented by 14% of samples.3

The human genome was first sequenced in 2003 and helped to unravel the complexities behind disease-causing alterations in our DNA. Although genetic testing has evolved a great deal since then, the original and ‘first generation’ method used to sequence the genome was ‘Sanger sequencing’.

Named after Fred Sanger who developed this in 1975, Sanger sequencing involves using DNA as a template to generate a set of fragments that differ in length. The fragments …

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  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

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