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Barwell et al. J Transl Genet Genom 2018;2:13 Journal of Translational
DOI: 10.20517/jtgg.2018.17 Genetics and Genomics

Review Open Access

Challenges in implementing genomic medicine: the
100,000 Genomes Project

Julian G. Barwell , Rory B.G. O’Sullivan , Laura K. Mansbridge , Joanna M. Lowry , Huw R. Dorkins 1
1
1
2
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1 Department of Clinical Genetics, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester LE1 5WW, UK.
2 School of Medicine, University of Leicester, George Davies Centre, Leicester LE1 7HA, UK.
Correspondence to: Dr. Julian G. Barwell, Department of Clinical Genetics, University Hospitals of Leicester NHS Trust, Leicester Royal
Infirmary, Leicester LE1 5WW, UK. E-mail: julian.barwell@uhl-tr.nhs.uk
How to cite this article: Barwell JG, O’Sullivan RBG, Mansbridge LK, Lowry JM, Dorkins HR. Challenges in implementing genomic
medicine: the 100,000 Genomes Project. J Transl Genet Genom 2018;2:13. https://doi.org/10.20517/jtgg.2018.17
Received: 27 June 2018 First Decision: 2 Aug 2018 Revised: 24 Aug 2018 Accepted: 27 Aug 2018 Published: 11 Sep 2018

Science Editor: Sheng-Ying Qin Copy Editor: Yuan-Li Wang Production Editor: Huan-Liang Wu

Abstract

Many important medical conditions may be the result of an inherited mutation in one of a number of different genes.
Technical advances have reduced the cost of whole genome sequencing and whole exome sequencing to a level where
it is now feasible to analyse multiple genes in one test. Every human carries several hundred potentially pathogenic
coding variants, so a major challenge is to understand which of these is relevant to the patient’s disease. This requires
considerable computing power, the use of international unaffected “normal” population and disease cohort databases,
clinical scientist input as well as a medical context provided by accurate phenotyping and understanding of Bayesian
probability. The guidelines of the American College of Medical Genetics provide a useful framework for the evaluation
and reporting of sequence variants. In England, the 100,000 Genomes Project was established within the National
Health Service to introduce these technologies into mainstream healthcare. From January 2019, genomic laboratory
hubs will deliver a genomics service. In this paper, we review what has been learnt from the project to date and consider
how other health care systems could use similar approaches.

Keywords: Genomic medicine, personalised medicine, road map, transformation

INTRODUCTION
Genomic medicine
Given the brief of this review to assess the impact of the 100,000 Genomes Project on clinical care, we de-
fine genomic medicine as the diagnosis, prediction, prognosis, prevention and/or treatment of disease and
disorders of the mind and body, using approaches informed or enabled by knowledge of the genome and
the molecules it encodes. In this paper, we focus on the use of DNA sequence data to aid in the diagnosis

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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