WGS500 is a collaborative project between the Wellcome Trust Centre for Human Genetics, the BRC Genomic Medicine Theme, and the technology company Illumina with the aim of evaluating the clinical utility of whole genome sequencing across a number of human diseases. Proposals were invited from clinicians for cases where standard genetic tests had proved negative or where no test was available. The genomes of five hundred patients and family members were sequenced spanning a range of diseases including Mendelian disorders, severe and early onset immunological conditions, and cancer, with the hope of identifying variants in novel genes or pathways to inform diagnosis, prognosis, and reproductive risk, or influence treatment selection. By mid-2013, this project had resulted in the conclusive identification of several new causative genes, with many more in validation, leading to the improvement of diagnostic genetic tests for inherited diseases in the NHS, and clearly demonstrating the value of this approach.
Babbs C, Roberts NA, Sanchez-Pulido L, McGowan SJ, Ahmed MR, Brown JM, Sabry MA, WGS500 Consortium, Bentley DR, McVean GA, Donnelly P, Gileadi O, Ponting CP, Higgs DR, Buckle VJ. Homozygous mutations in a predicted endonuclease are a novel cause of congenital dyserythropoietic anemia type I. Haematologica 2013; 98(9): 1383-7
Cossins J, Belaya K, Hicks D, Salih MA, Finlayson S, Carboni N, Liu WW, Maxwell S, Zoltowska K, Farsani GT, Laval S, Seidhamed MZ, WGS500 consortium, Donnelly P, Bentley D, McGowan SJ, Müller J, Palace J, Lochmüller H, Beeson D. Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain 2013; 136: 944–56
Lise S, Clarkson Y, Perkins E, Kwasniewska A, Akha ES, Schnekenberg RP, Suminaite D, Hope J, Baker I, Gregory L, Green A, Allan C, Lamble S, Jayawant S, Quaghebeur G, Cader MZ, Hughes S, Armstrong RJE, Kanapin A, Rimmer A, Lunter G, Mathieson I, Cazier J-B, Buck D, Taylor JC, Bentley DB, McVean G, Donnelly P, Knight SJL, Jackson M, Ragoussis J, Németh AH. Recessive Mutations in SPTBN2 Implicate β-III Spectrin in Both Cognitive and Motor Development. PLoS One 2012 Dec; 8(12): e1003074
Palles C, Cazier J-B, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Almeida EG, Salguero I, Sherborne A, Chubb D, Carvajal-Carmona LG, Ma Y, Kaur K, Dobbins S, Barclay E, Gorman M, Martin L, Kovac MB, Humphray S, The CORGI Consortium, The WGS500 Consortium, Lucassen A, Holmes CC, Bentley D7, Donnelly P, Taylor JC, Petridis C, Roylance R, Sawyer EJ, Kerr DJ, Clark S, Grimes J, Kearsey SE, Thomas HJW, McVean G, Houlston RS, Tomlinson I. Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nature Genetics 2013 Feb; 45(2): 136-43
Sharma VP, Fenwick AL, Brockop MS, McGowan SJ, Goos JAC, Hoogeboom AJM, Brady AF, Jeelani NO, Lynch SA, Mulliken JB, Murray DJ, Phipps JM, Sweeney E, Tomkins SE, Wilson LC, Bennett S, Cornall RJ, Broxholme JB, Kanapin A, WGS500 Consortium, Johnson D, Wall SA, van der Spek PJ, Mathijssen IMJ, Maxson RE, Twigg SRF, Wilkie AOM. Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis. Nature Genetics 2013 Mar; 45(3): 304-7