Dr Matthew Hurles

Matt moved to the Wellcome Trust Sanger Institute in 2003 to establish a group combining his interests in medical and population genetics.

Matt graduated with a degree in Biochemistry from Oxford University in 1996, and received his PhD from the University of Leicester in 1999 for work on the population genetics of human Y chromosomal polymorphisms. He then worked as a postdoctoral research fellow in population genetics at the University of Cambridge, focusing on the prehistory of Pacific populations and patterns of molecular evolution in duplicated sequences. During his postdoctoral research Matt established the molecular mechanism underlying a recurrent deletion of part of the Y chromosome, which causes male infertility.

Since 2003, Matt has led a major initiative to characterise structural variation in the human genome, and integrate this knowledge into disease and population genetic studies. This research combines large-scale data generation together with novel statistical analyses, and resulted in the first published genome-wide map of copy number variation in 2006, and along with Manolis Dermitzakis in 2007, demonstrated the impact of this form of variation on gene expression. His group has also developed novel experimental methods to probe the mutational mechanisms underlying genetic variation, which, in 2008, allowed identification of clinical syndromes that are being under-diagnosed. More recently, Dr Hurles has lead the construction of a comprehensive map of common copy number variation, and its integration into studies of common disease susceptibility, published in Nature in 2010. Dr Hurles also co-led, with Dr Sadaf Farooqi, the identification of nested microdeletions, which cause severe early-onset obesity, published in Nature in 2010. Dr Hurles is leading efforts at the Wellcome Trust Sanger Institute to apply genome-wide resequencing methods to the study of rare diseases.

In 2009, Matt was awarded the Balfour Lecture by the Genetics Society.

Matt currently has a leadership role in several large consortia, including the 1000 genomes project, the Deciphering Developmental Disorders initiative and the UK10K project.

Selected Publications

• A map of human genome variation from population-scale sequencing.

  1000 Genomes Project Consortium, Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME and McVean GA

  Nature 2010;467;7319;1061-73

  PUBMED: 20981092; PMC: 3042601; DOI: 10.1038/nature09534

• Characterising and predicting haploinsufficiency in the human genome.

  Huang N, Lee I, Marcotte EM and Hurles ME

  PLoS genetics 2010;6;10;e1001154

  PUBMED: 20976243; PMC: 2954820; DOI: 10.1371/journal.pgen.1001154

• Mutation spectrum revealed by breakpoint sequencing of human germline CNVs.

  Conrad DF, Bird C, Blackburne B, Lindsay S, Mamanova L, Lee C, Turner DJ and Hurles ME

  Nature genetics 2010;42;5;385-91

  PUBMED: 20364136; PMC: 3428939; DOI: 10.1038/ng.564

• Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.

  Wellcome Trust Case Control Consortium, Craddock N, Hurles ME, Cardin N, Pearson RD, Plagnol V, Robson S, Vukcevic D, Barnes C, Conrad DF, Giannoulatou E, Holmes C, Marchini JL, Stirrups K, Tobin MD, Wain LV, Yau C, Aerts J, Ahmad T, Andrews TD, Arbury H, Attwood A, Auton A, Ball SG, Balmforth AJ, Barrett JC, Barroso I, Barton A, Bennett AJ, Bhaskar S, Blaszczyk K, Bowes J, Brand OJ, Braund PS, Bredin F, Breen G, Brown MJ, Bruce IN, Bull J, Burren OS, Burton J, Byrnes J, Caesar S, Clee CM, Coffey AJ, Connell JM, Cooper JD, Dominiczak AF, Downes K, Drummond HE, Dudakia D, Dunham A, Ebbs B, Eccles D, Edkins S, Edwards C, Elliot A, Emery P, Evans DM, Evans G, Eyre S, Farmer A, Ferrier IN, Feuk L, Fitzgerald T, Flynn E, Forbes A, Forty L, Franklyn JA, Freathy RM, Gibbs P, Gilbert P, Gokumen O, Gordon-Smith K, Gray E, Green E, Groves CJ, Grozeva D, Gwilliam R, Hall A, Hammond N, Hardy M, Harrison P, Hassanali N, Hebaishi H, Hines S, Hinks A, Hitman GA, Hocking L, Howard E, Howard P, Howson JM, Hughes D, Hunt S, Isaacs JD, Jain M, Jewell DP, Johnson T, Jolley JD, Jones IR, Jones LA, Kirov G, Langford CF, Lango-Allen H, Lathrop GM, Lee J, Lee KL, Lees C, Lewis K, Lindgren CM, Maisuria-Armer M, Maller J, Mansfield J, Martin P, Massey DC, McArdle WL, McGuffin P, McLay KE, Mentzer A, Mimmack ML, Morgan AE, Morris AP, Mowat C, Myers S, Newman W, Nimmo ER, O'Donovan MC, Onipinla A, Onyiah I, Ovington NR, Owen MJ, Palin K, Parnell K, Pernet D, Perry JR, Phillips A, Pinto D, Prescott NJ, Prokopenko I, Quail MA, Rafelt S, Rayner NW, Redon R, Reid DM, Renwick, Ring SM, Robertson N, Russell E, St Clair D, Sambrook JG, Sanderson JD, Schuilenburg H, Scott CE, Scott R, Seal S, Shaw-Hawkins S, Shields BM, Simmonds MJ, Smyth DJ, Somaskantharajah E, Spanova K, Steer S, Stephens J, Stevens HE, Stone MA, Su Z, Symmons DP, Thompson JR, Thomson W, Travers ME, Turnbull C, Valsesia A, Walker M, Walker NM, Wallace C, Warren-Perry M, Watkins NA, Webster J, Weedon MN, Wilson AG, Woodburn M, Wordsworth BP, Young AH, Zeggini E, Carter NP, Frayling TM, Lee C, McVean G, Munroe PB, Palotie A, Sawcer SJ, Scherer SW, Strachan DP, Tyler-Smith C, Brown MA, Burton PR, Caulfield MJ, Compston A, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Mathew CG, Pembrey M, Satsangi J, Stratton MR, Worthington J, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand W, Parkes M, Rahman N, Todd JA, Samani NJ and Donnelly P

  Nature 2010;464;7289;713-20

  PUBMED: 20360734; PMC: 2892339; DOI: 10.1038/nature08979

• Origins and functional impact of copy number variation in the human genome.

  Conrad DF, Pinto D, Redon R, Feuk L, Gokcumen O, Zhang Y, Aerts J, Andrews TD, Barnes C, Campbell P, Fitzgerald T, Hu M, Ihm CH, Kristiansson K, Macarthur DG, Macdonald JR, Onyiah I, Pang AW, Robson S, Stirrups K, Valsesia A, Walter K, Wei J, Wellcome Trust Case Control Consortium, Tyler-Smith C, Carter NP, Lee C, Scherer SW and Hurles ME

  Nature 2010;464;7289;704-12

  PUBMED: 19812545; PMC: 3330748; DOI: 10.1038/nature08516

• Large, rare chromosomal deletions associated with severe early-onset obesity.

  Bochukova EG, Huang N, Keogh J, Henning E, Purmann C, Blaszczyk K, Saeed S, Hamilton-Shield J, Clayton-Smith J, O'Rahilly S, Hurles ME and Farooqi IS

  Nature 2010;463;7281;666-70

  PUBMED: 19966786; PMC: 3108883; DOI: 10.1038/nature08689

• A robust statistical method for case-control association testing with copy number variation.

  Barnes C, Plagnol V, Fitzgerald T, Redon R, Marchini J, Clayton D and Hurles ME

  Nature genetics 2008;40;10;1245-52

  PUBMED: 18776912; PMC: 2784596; DOI: 10.1038/ng.206

• Germline rates of de novo meiotic deletions and duplications causing several genomic disorders.

  Turner DJ, Miretti M, Rajan D, Fiegler H, Carter NP, Blayney ML, Beck S and Hurles ME

  Nature genetics 2008;40;1;90-5

  PUBMED: 18059269; PMC: 2669897; DOI: 10.1038/ng.2007.40

• Relative impact of nucleotide and copy number variation on gene expression phenotypes.

  Stranger BE, Forrest MS, Dunning M, Ingle CE, Beazley C, Thorne N, Redon R, Bird CP, de Grassi A, Lee C, Tyler-Smith C, Carter N, Scherer SW, Tavaré S, Deloukas P, Hurles ME and Dermitzakis ET

  Science (New York, N.Y.) 2007;315;5813;848-53

  PUBMED: 17289997; PMC: 2665772; DOI: 10.1126/science.1136678

• Global variation in copy number in the human genome.

  Redon R, Ishikawa S, Fitch KR, Feuk L, Perry GH, Andrews TD, Fiegler H, Shapero MH, Carson AR, Chen W, Cho EK, Dallaire S, Freeman JL, González JR, Gratacòs M, Huang J, Kalaitzopoulos D, Komura D, MacDonald JR, Marshall CR, Mei R, Montgomery L, Nishimura K, Okamura K, Shen F, Somerville MJ, Tchinda J, Valsesia A, Woodwark C, Yang F, Zhang J, Zerjal T, Zhang J, Armengol L, Conrad DF, Estivill X, Tyler-Smith C, Carter NP, Aburatani H, Lee C, Jones KW, Scherer SW and Hurles ME

  Nature 2006;444;7118;444-54

  PUBMED: 17122850; PMC: 2669898; DOI: 10.1038/nature05329

Related links:

• UK10K
• CNV project