Archive Page: Dr Harold Swerdlow

Harold Swerdlow is vice president of Technology Innovation at the New York Genome Center. From January 2008 to May 2014 he was head of Sequencing Research and Development at the Sanger Institute. His role involved many aspects of next-generation DNA sequencing technology and included advising on the Illumina production facility, helping to formulate the Institute's strategy for acquiring future sequencing technologies and oversight of the research and development team.

Harold received his PhD at the University of Utah, developing capillary electrophoresis for DNA sequencing. He went on to join the Faculty in the Human Genetics department at the University, managing various molecular biotechnology projects related to genomics.

At the Karolinska Institute in Sweden, he was the Unit Coordinator of the Genomics Technologies Unit and Director of the Microarray Core Facility in the newly formed Center for Genomics Research. His first role in the UK was as Senior Director of Research at Solexa Ltd. (now Illumina, Inc.), responsible for developing the most widely used technology for next-generation DNA sequencing. Before joining the Sanger Institute, Harold was the Chief Technology Officer (CTO) at Dolomite Ltd., a microfabrication and microfluidics consultancy.

At the Institute, Harold's research interests centred on using miniaturisation and microfluidics to solve sample-preparation bottlenecks created by high-throughput sequencing instruments.


Team members

Naomi Park
Staff Scientist
Michael Quail R and D Team Leader

Naomi Park

- Staff Scientist

In 2002 I graduated from the University of Surrey with a degree in Analytical and Environmental Chemistry, and commenced my PhD in the Chemistry department at the University of Southampton shortly after.

My thesis involved developing a novel method of genotyping SNPs by Mass Spectrometry, and modification of primers to improve multiplexed PCR. After completing my PhD in 2007 I worked in the metabolomics group at GlaxoSmithKline, before moving to Sanger's Genotyping facility in 2008. I predominantly used the Sequenom platform to genotype Copy Number Variation in addition to SNPs. In 2010 I managed several platforms within the Microarray facility.


Since April 2011 I have worked in the Sequencing Technology Development team, whose focus is upon the progression of technologies and protocols in order to support the Institutes sequencing production teams and faculty researchers.

My current project is to establish a robust mate pair library preparation method to generate libraries with inserts ranging from 3kb upwards. A method which generates a minimal number of false positive mate reads with a range of genomes, of varying sample quality, will aid applications including de novo sequencing, genome finishing, and structural variant detection.


  • Transferrin and HFE genes interact in Alzheimer's disease risk: the Epistasis Project.

    Lehmann DJ, Schuur M, Warden DR, Hammond N, Belbin O, Kölsch H, Lehmann MG, Wilcock GK, Brown K, Kehoe PG, Morris CM, Barker R, Coto E, Alvarez V, Deloukas P, Mateo I, Gwilliam R, Combarros O, Arias-Vásquez A, Aulchenko YS, Ikram MA, Breteler MM, van Duijn CM, Oulhaj A, Heun R, Cortina-Borja M, Morgan K, Robson K and Smith AD

    Oxford Project to Investigate Memory and Ageing, University Department of Physiology, Anatomy and Genetics, Oxford, UK.

    Iron overload may contribute to the risk of Alzheimer's disease (AD). In the Epistasis Project, with 1757 cases of AD and 6295 controls, we studied 4 variants in 2 genes of iron metabolism: hemochromatosis (HFE) C282Y and H63D, and transferrin (TF) C2 and -2G/A. We replicated the reported interaction between HFE 282Y and TF C2 in the risk of AD: synergy factor, 1.75 (95% confidence interval, 1.1-2.8, p = 0.02) in Northern Europeans. The synergy factor was 3.1 (1.4-6.9; 0.007) in subjects with the APOEε4 allele. We found another interaction, between HFE 63HH and TF -2AA, markedly modified by age. Both interactions were found mainly or only in Northern Europeans. The interaction between HFE 282Y and TF C2 has now been replicated twice, in altogether 2313 cases of AD and 7065 controls, and has also been associated with increased iron load. We therefore suggest that iron overload may be a causative factor in the development of AD. Treatment for iron overload might thus be protective in some cases.

    Funded by: Medical Research Council: G0400074, G0400546, G0502157, G0900652, G1100540

    Neurobiology of aging 2012;33;1;202.e1-13

  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

    International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, Edkins S, Gray E, Booth DR, Potter SC, Goris A, Band G, Oturai AB, Strange A, Saarela J, Bellenguez C, Fontaine B, Gillman M, Hemmer B, Gwilliam R, Zipp F, Jayakumar A, Martin R, Leslie S, Hawkins S, Giannoulatou E, D'alfonso S, Blackburn H, Martinelli Boneschi F, Liddle J, Harbo HF, Perez ML, Spurkland A, Waller MJ, Mycko MP, Ricketts M, Comabella M, Hammond N, Kockum I, McCann OT, Ban M, Whittaker P, Kemppinen A, Weston P, Hawkins C, Widaa S, Zajicek J, Dronov S, Robertson N, Bumpstead SJ, Barcellos LF, Ravindrarajah R, Abraham R, Alfredsson L, Ardlie K, Aubin C, Baker A, Baker K, Baranzini SE, Bergamaschi L, Bergamaschi R, Bernstein A, Berthele A, Boggild M, Bradfield JP, Brassat D, Broadley SA, Buck D, Butzkueven H, Capra R, Carroll WM, Cavalla P, Celius EG, Cepok S, Chiavacci R, Clerget-Darpoux F, Clysters K, Comi G, Cossburn M, Cournu-Rebeix I, Cox MB, Cozen W, Cree BA, Cross AH, Cusi D, Daly MJ, Davis E, de Bakker PI, Debouverie M, D'hooghe MB, Dixon K, Dobosi R, Dubois B, Ellinghaus D, Elovaara I, Esposito F, Fontenille C, Foote S, Franke A, Galimberti D, Ghezzi A, Glessner J, Gomez R, Gout O, Graham C, Grant SF, Guerini FR, Hakonarson H, Hall P, Hamsten A, Hartung HP, Heard RN, Heath S, Hobart J, Hoshi M, Infante-Duarte C, Ingram G, Ingram W, Islam T, Jagodic M, Kabesch M, Kermode AG, Kilpatrick TJ, Kim C, Klopp N, Koivisto K, Larsson M, Lathrop M, Lechner-Scott JS, Leone MA, Leppä V, Liljedahl U, Bomfim IL, Lincoln RR, Link J, Liu J, Lorentzen AR, Lupoli S, Macciardi F, Mack T, Marriott M, Martinelli V, Mason D, McCauley JL, Mentch F, Mero IL, Mihalova T, Montalban X, Mottershead J, Myhr KM, Naldi P, Ollier W, Page A, Palotie A, Pelletier J, Piccio L, Pickersgill T, Piehl F, Pobywajlo S, Quach HL, Ramsay PP, Reunanen M, Reynolds R, Rioux JD, Rodegher M, Roesner S, Rubio JP, Rückert IM, Salvetti M, Salvi E, Santaniello A, Schaefer CA, Schreiber S, Schulze C, Scott RJ, Sellebjerg F, Selmaj KW, Sexton D, Shen L, Simms-Acuna B, Skidmore S, Sleiman PM, Smestad C, Sørensen PS, Søndergaard HB, Stankovich J, Strange RC, Sulonen AM, Sundqvist E, Syvänen AC, Taddeo F, Taylor B, Blackwell JM, Tienari P, Bramon E, Tourbah A, Brown MA, Tronczynska E, Casas JP, Tubridy N, Corvin A, Vickery J, Jankowski J, Villoslada P, Markus HS, Wang K, Mathew CG, Wason J, Palmer CN, Wichmann HE, Plomin R, Willoughby E, Rautanen A, Winkelmann J, Wittig M, Trembath RC, Yaouanq J, Viswanathan AC, Zhang H, Wood NW, Zuvich R, Deloukas P, Langford C, Duncanson A, Oksenberg JR, Pericak-Vance MA, Haines JL, Olsson T, Hillert J, Ivinson AJ, De Jager PL, Peltonen L, Stewart GJ, Hafler DA, Hauser SL, McVean G, Donnelly P and Compston A

    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.

    Funded by: Department of Health: PDA/02/06/016; Medical Research Council: G0100594, G0400017, G0700061, G0901310, G0901461, G19/2; Multiple Sclerosis Society: 898; NCI NIH HHS: CA104021; NCRR NIH HHS: RR020092, RR024992, UL1 RR024992; NIAID NIH HHS: AI076544; NINDS NIH HHS: NS032830, NS049477, NS049510, NS067305, NS19142, NS26799, NS43559, R01 NS026799, R01 NS049477, R01 NS049477-06A1; PHS HHS: K23N/S048869; Wellcome Trust: 068545/Z/02, 075491/Z/04/Z, 084702, 085475, 085475/B/08/Z, 085475/Z/08/Z, 090532

    Nature 2011;476;7359;214-9

  • Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case-control study in South Asia and updated meta-analysis of Europeans.

    Saleheen D, Alexander M, Rasheed A, Wormser D, Soranzo N, Hammond N, Butterworth A, Zaidi M, Haycock P, Bumpstead S, Potter S, Blackburn H, Gray E, Di Angelantonio E, Kaptoge S, Shah N, Samuel M, Janjua A, Sheikh N, Haider SR, Murtaza M, Ahmad U, Hakeem A, Memon MA, Mallick NH, Azhar M, Samad A, Rasheed SZ, Gardezi AR, Memon NA, Ghaffar A, Memon FU, Zaman KS, Kundi A, Yaqoob Z, Cheema LA, Qamar N, Faruqui A, Jooma R, Niazi JH, Hussain M, Kumar K, Saleem A, Kumar K, Daood MS, Memon F, Gul AA, Abbas S, Zafar J, Shahid F, Memon Z, Bhatti SM, Kayani W, Ali SS, Fahim M, Ishaq M, Frossard P, Deloukas P and Danesh J

    Center for Non-Communicable Diseases, Karachi, Pakistan.

    Objective: To examine variants at the 9p21 locus in a case-control study of acute myocardial infarction (MI) in Pakistanis and to perform an updated meta-analysis of published studies in people of European ancestry.

    A total of 1851 patients with first-ever confirmed MI and 1903 controls were genotyped for 89 tagging single-nucleotide polymorphisms at locus 9p21, including the lead variant (rs1333049) identified by the Wellcome Trust Case Control Consortium. Minor allele frequencies and extent of linkage disequilibrium observed in Pakistanis were broadly similar to those seen in Europeans. In the Pakistani study, 6 variants were associated with MI (P<10(-2)) in the initial sample set, and in an additional 741 cases and 674 controls in whom further genotyping was performed for these variants. For Pakistanis, the odds ratio for MI was 1.13 (95% CI, 1.05 to 1.22; P=2 x 10(-3)) for each copy of the C allele at rs1333049. In comparison, a meta-analysis of studies in Europeans yielded an odds ratio of 1.31 (95% CI, 1.26 to 1.37) for the same variant (P=1 x 10(-3) for heterogeneity). Meta-analyses of 23 variants, in up to 38,250 cases and 84,820 controls generally yielded higher values in Europeans than in Pakistanis.

    Conclusions: To our knowledge, this study provides the first demonstration that variants at the 9p21 locus are significantly associated with MI risk in Pakistanis. However, association signals at this locus were weaker in Pakistanis than those in European studies.

    Funded by: British Heart Foundation: RG/08/014/24067; Medical Research Council; Wellcome Trust

    Arteriosclerosis, thrombosis, and vascular biology 2010;30;7;1467-73

  • Low-density lipoprotein receptor-related protein 5 polymorphisms are associated with bone mineral density in Greek postmenopausal women: an interaction with calcium intake.

    Stathopoulou MG, Dedoussis GV, Trovas G, Katsalira A, Hammond N, Deloukas P and Lyritis GP

    Department of Dietetics and Nutrition, Harokopio University, 17671 Athens, Greece.

    The low-density lipoprotein receptor-related protein 5 (LRP5) has been shown to play a significant role in bone biology. This study aimed to assess the association of four common polymorphisms of the LRP5 gene with bone mineral density (BMD) and possible genexcalcium intake interactions in Greek postmenopausal women. For this observational cross-sectional association study, healthy postmenopausal women (N=578) were recruited (between December 2006 and January 2008) and genotyped for four polymorphisms (rs1784235, rs491347, rs4988321, and rs4988330) in the LRP5 gene. Measurements of BMD were performed and detailed medical, dietary, and anthropometric data were recorded. Student t tests and multiple linear regression models were applied after controlling for potential covariates (ie, age, weight, height, and calcium intake). None of the polymorphisms was associated with the presence of osteoporosis, fractures, and hip BMD. All polymorphisms were associated with unadjusted spine BMD, with the exception of rs4988330. Only rs4988321 was associated with adjusted spine BMD, where the presence of the A allele was associated with significantly lower spine BMD compared with the GG genotype (P=0.002). An interaction of the rs4988321 polymorphism with calcium intake (P=0.016) was found. The carriers of the A allele demonstrated significantly lower spine BMD compared to GG homozygotes (P=0.001) only in the lowest calcium intake group (<680 mg/day), whereas in the highest calcium intake group no differences were found in BMD between genotypes. These findings demonstrate that both rs4988321 polymorphism and its interaction with calcium intake are associated with BMD, whereas higher calcium intake was shown to decrease the negative effect of this polymorphism on BMD.

    Journal of the American Dietetic Association 2010;110;7;1078-83

  • 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

    Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.

    Funded by: Arthritis Research UK: 17552; Chief Scientist Office: CZB/4/540, ETM/137, ETM/75; Medical Research Council: G0000934, G0400874, G0500115, G0501942, G0600329, G0600705, G0700491, G0701003, G0701420, G0701810, G0701810(85517), G0800383, G0800759, G19/9, G90/106, G9521010, MC_UP_A390_1107; Wellcome Trust: 061858, 083948, 089989

    Nature 2010;464;7289;713-20

  • New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

    Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, Wheeler E, Glazer NL, Bouatia-Naji N, Gloyn AL, Lindgren CM, Mägi R, Morris AP, Randall J, Johnson T, Elliott P, Rybin D, Thorleifsson G, Steinthorsdottir V, Henneman P, Grallert H, Dehghan A, Hottenga JJ, Franklin CS, Navarro P, Song K, Goel A, Perry JR, Egan JM, Lajunen T, Grarup N, Sparsø T, Doney A, Voight BF, Stringham HM, Li M, Kanoni S, Shrader P, Cavalcanti-Proença C, Kumari M, Qi L, Timpson NJ, Gieger C, Zabena C, Rocheleau G, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, McCarroll SA, Payne F, Roccasecca RM, Pattou F, Sethupathy P, Ardlie K, Ariyurek Y, Balkau B, Barter P, Beilby JP, Ben-Shlomo Y, Benediktsson R, Bennett AJ, Bergmann S, Bochud M, Boerwinkle E, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Charpentier G, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Cornelis M, Crawford G, Crisponi L, Day IN, de Geus EJ, Delplanque J, Dina C, Erdos MR, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Fox CS, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Groves CJ, Grundy S, Gwilliam R, Gyllensten U, Hadjadj S, Hallmans G, Hammond N, Han X, Hartikainen AL, Hassanali N, Hayward C, Heath SC, Hercberg S, Herder C, Hicks AA, Hillman DR, Hingorani AD, Hofman A, Hui J, Hung J, Isomaa B, Johnson PR, Jørgensen T, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Lyssenko V, Mahley R, Mangino M, Manning AK, Martínez-Larrad MT, McAteer JB, McCulloch LJ, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Morken MA, Mukherjee S, Naitza S, Narisu N, Neville MJ, Oostra BA, Orrù M, Pakyz R, Palmer CN, Paolisso G, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rathmann W, Rayner NW, Rice K, Ripatti S, Rivadeneira F, Roden M, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Scott LJ, Seedorf U, Sharp SJ, Shields B, Sigurethsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Thorand B, Tichet J, Tönjes A, Tuomi T, Uitterlinden AG, van Dijk KW, van Hoek M, Varma D, Visvikis-Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Walters GB, Ward KL, Watkins H, Weedon MN, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zeggini E, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, DIAGRAM Consortium, GIANT Consortium, Global BPgen Consortium, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Hattersley AT, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano-Ríos M, Morris AD, Lind L, Palmer LJ, Hu FB, Franks PW, Ebrahim S, Marmot M, Kao WH, Pankow JS, Sampson MJ, Kuusisto J, Laakso M, Hansen T, Pedersen O, Pramstaller PP, Wichmann HE, Illig T, Rudan I, Wright AF, Stumvoll M, Campbell H, Wilson JF, Anders Hamsten on behalf of Procardis Consortium, MAGIC investigators, Bergman RN, Buchanan TA, Collins FS, Mohlke KL, Tuomilehto J, Valle TT, Altshuler D, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Frayling TM, Ferrucci L, Kong A, Thorsteinsdottir U, Stefansson K, van Duijn CM, Aulchenko YS, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Abecasis GR, Wareham NJ, Sladek R, Froguel P, Watanabe RM, Meigs JB, Groop L, Boehnke M, McCarthy MI, Florez JC and Barroso I

    Department of Biostatistics, Boston University School of Public Health, Massachusetts, USA.

    Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

    Funded by: Chief Scientist Office: CZB/4/710; Medical Research Council: G0600705, G0601261, G0700222, G0700222(81696), G0701863, G0801056, G19/35, MC_U106179471, MC_U106188470, MC_U127561128, MC_U127592696, MC_U137686854, MC_UP_A620_1014, MC_UP_A620_1015; NIDDK NIH HHS: K24 DK080140-05, P30 DK040561-14, P30 DK072488, R01 DK029867, R01 DK072193, R01 DK078616-01A1; The Dunhill Medical Trust: R69/0208; Wellcome Trust: 064890, 077011, 077016, 081682, 088885, 089061, 091746

    Nature genetics 2010;42;2;105-16

  • The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project.

    Combarros O, Warden DR, Hammond N, Cortina-Borja M, Belbin O, Lehmann MG, Wilcock GK, Brown K, Kehoe PG, Barber R, Coto E, Alvarez V, Deloukas P, Gwilliam R, Heun R, Kölsch H, Mateo I, Oulhaj A, Arias-Vásquez A, Schuur M, Aulchenko YS, Ikram MA, Breteler MM, van Duijn CM, Morgan K, Smith AD and Lehmann DJ

    Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital (University of Cantabria), 39008 Santander, Spain.

    Background: The loss of noradrenergic neurones of the locus coeruleus is a major feature of Alzheimer's disease (AD). Dopamine β-hydroxylase (DBH) catalyses the conversion of dopamine to noradrenaline. Interactions have been reported between the low-activity -1021T allele (rs1611115) of DBH and polymorphisms of the pro-inflammatory cytokine genes, IL1A and IL6, contributing to the risk of AD. We therefore examined the associations with AD of the DBH -1021T allele and of the above interactions in the Epistasis Project, with 1757 cases of AD and 6294 elderly controls.

    Methods: We genotyped eight single nucleotide polymorphisms (SNPs) in the three genes, DBH, IL1A and IL6. We used logistic regression models and synergy factor analysis to examine potential interactions and associations with AD.

    Results: We found that the presence of the -1021T allele was associated with AD: odds ratio = 1.2 (95% confidence interval: 1.06-1.4, p = 0.005). This association was nearly restricted to men < 75 years old: odds ratio = 2.2 (1.4-3.3, 0.0004). We also found an interaction between the presence of DBH -1021T and the -889TT genotype (rs1800587) of IL1A: synergy factor = 1.9 (1.2-3.1, 0.005). All these results were consistent between North Europe and North Spain.

    Conclusions: Extensive, previous evidence (reviewed here) indicates an important role for noradrenaline in the control of inflammation in the brain. Thus, the -1021T allele with presumed low activity may be associated with misregulation of inflammation, which could contribute to the onset of AD. We suggest that such misregulation is the predominant mechanism of the association we report here.

    Funded by: Medical Research Council: G0400546

    BMC medical genetics 2010;11;162

  • Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease.

    Combarros O, van Duijn CM, Hammond N, Belbin O, Arias-Vásquez A, Cortina-Borja M, Lehmann MG, Aulchenko YS, Schuur M, Kölsch H, Heun R, Wilcock GK, Brown K, Kehoe PG, Harrison R, Coto E, Alvarez V, Deloukas P, Mateo I, Gwilliam R, Morgan K, Warden DR, Smith AD and Lehmann DJ

    Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Marqués de Valdecilla University Hospital (University of Cantabria), 39008 Santander, Spain.

    Background: Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10).

    Methods: We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls.

    Results: We replicated the interaction. For IL6 rs2069837 AA x IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10-2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E epsilon4 (APOEepsilon4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded.

    Conclusion: We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD.

    Funded by: Medical Research Council: G0400546

    Journal of neuroinflammation 2009;6;22

  • Rapid mass spectrometric identification of human genomic polymorphisms using multiplexed photocleavable mass-tagged probes and solid phase capture.

    Hammond N, Koumi P, Langley GJ, Lowe A and Brown T

    School of Chemistry, University of Southampton, Southampton, UK.

    A mass spectrometric approach for rapid and simultaneous detection of several single nucleotide polymorphisms (SNPs) is reported. Oligonucleotide single base extension (SBE) primers, labelled at the 5'-end with photocleavable, quaternised and brominated peptidic mass tags, are extended by a mixture of the four dideoxynucleotides of which one is biotinylated. The 3'-biotinylated extension products are captured by streptavidin-coated solid phase magnetic beads, whilst non-biotinylated extension products and unreacted primers are washed away. Quaternised and brominated mass tags, cleaved from captured extension products during analysis by matrix-assisted laser desorption/ionisation-time-of-flight (MALDI-TOF) MS, are detected at pmol levels. This method is applied to the analysis of mitochondrial DNA polymorphisms for the purpose of human identification.

    Organic & biomolecular chemistry 2007;5;12;1878-85

Michael Quail Sequencing R and D Team Leader

January-October 2010: Library Coordinator within the WTSI sequencing division where I managed the library construction, 454 and mapping and archive groups.

2007-2010: Head of sequencing library construction.

1997-2007: Project Leader Pathogen Subcloning at Sanger.

23/2/1997: Arrived at Sanger.

1990-1997: Postdoctoral research with Professor John Guest, FRS (University of Sheffield). Regulation of the PDH complex and the function of iron-storage proteins in E.coli.

1986-1990: Ph.D with Dr. S.L. Kelly (University of Sheffield) investigating the cytochrome P450 system of Botrytis cinerea.

1986-1988: R and D Biotechnologist, Quest International (Unilever).

1983-1986: B.Sc Biocehmistry,University of Hull.


I am team leader of the Sequencing research and development group at the Wellcome Trust Sanger Institute. We are involved in evaluating new sequencing technologies and developing new sequencing applications and protocols.

As well as managing the group I am actively optimising protocols and automation techniques for Illumina library preparation and am evaluating the Illumina MiSeq platform.


  • Relationship between dietary protein concentration and serum trypsin-like immunoreactivity in dogs.

    Carro T and Williams DA

    Department of Small Animal Clinical Sciences, University of Florida, Gainesville 32610.

    Serum trypsinogen concentration was studied in 6 adult mixed-breed dogs randomly fed diets containing 6.8, 31.4, or 39.7% protein (dry weight) for 3 weeks each. Blood was collected on days 20, 21, and 22 of each feeding period, and serum trypsinogen concentrations were determined by radioimmunoassay of trypsin-like immunoreactivity (TLI). Mean serum TLI concentrations for each dog fed each diet were compared. A significant (P less than 0.05) positive linear relationship (P less than 0.02) was determined between serum TLI concentrations and the percentage of dietary protein. Mean serum TLI concentrations for each dog fed all diets ranged from 5.7 to 20.2 micrograms/L.

    American journal of veterinary research 1989;50;12;2105-7

  • Prediction error variance and restricted maximum likelihood estimation for animal model with relationship grouping.

    Da Y, Grossman M and Misztal I

    Department of Animal Sciences, University of Illinois, Urbana 61801.

    Genetic evaluation using animal model with relationship grouping has been shown to be feasible. However, algorithms were unavailable for prediction error variance and REML estimation of variance components. This paper shows that prediction error variance of an estimable function of the total merit of additive genetic and group effects is a simple function of a generalized inverse of the coefficient matrix for a transformed mixed model equation or of the inverse of the coefficient matrix when it is restricted to full rank. The REML algorithms, using the transformed equation, having slightly more complicated expressions than usual but could be more feasible computationally. Formulae for prediction error variance apply in general. The REML algorithms are extended to an animal model with an arbitrary number of random factors and can be extended to estimate covariance components.

    Journal of dairy science 1989;72;8;2125-35

  • [Sense and nonsense of examinations in hematogenous and exogenous intra-ocular infections].

    Martenet AC

    Clinique Ophtalmologique universitaire de Zurich.

    Diagnosis of intraocular inflammations can be difficult, particularly if the patient is suffering from immunodeficiency. Among the endogenous inflammations this applies mainly to cases of hyaloretinitis caused by Candida or other fungi, often presenting as an acute hyalitis with sudden onset; the various ocular complications of AIDS, especially those due to toxoplasmosis (rare) and cytomegalovirus, and lyme disease, which can occasionally cause chronic panuveitis. Among the exogenous cases it applies to postoperative and posttraumatic endophthalmitis. In all these cases the diagnosis has to be established clinically if possible, since, as a consequence of the immunodeficiency, serology is hardly helpful, and only biopsy (of the vitreous) may provide additional information. Rapid diagnosis is very important because of the urgent need for therapy.

    Klinische Monatsblätter für Augenheilkunde 1989;194;5;359-60

  • Variability of serum phenytoin concentrations in nursing home patients.

    Mooradian AD, Hernandez L, Tamai IC and Marshall C

    Geriatric Research, Education and Clinical Center, Sepulveda (Calif) Veterans Administration Medical Center.

    A marked variability in serum phenytoin concentrations was observed in an elderly nursing home resident. To determine the prevalence of this problem, 15 frail nursing home patients who were receiving phenytoin therapy were studied over a mean follow-up period of 10.6 +/- 0.89 months. The mean number of serum phenytoin level measurements during this period was 13.1 +/- 1.5. For a given individual, there was no variation in phenytoin dose or preparation administered. All the patients had a difference of more than 50% between the highest and the lowest serum phenytoin levels, and in five patients (33%), the difference exceeded 150%. The change in serum phenytoin level was temporally related to influenza vaccination in only three patients. The form of phenytoin was not a significant determinant of the variability in this patient population, nor did enteral feeding have any effect. It is recommended that nursing home patients receiving phenytoin therapy have periodic serum phenytoin measurements obtained, even in the absence of seizures or classic signs of phenytoin toxicity.

    Archives of internal medicine 1989;149;4;890-2

  • A serological survey of Lassa fever in Liberia.

    Bloch A

    A serological survey was undertaken at four Liberian hospitals in 1974 in which serum samples were taken from 104 health workers and 61 patients. Six persons had Lassa fever antibodies: four midwives and two students of midwifery. Of those persons who had lived in Loffa County, 4 of 22 midwives were seropositive whereas none of the other 39 residents were positive (P = 0.014).

    Bulletin of the World Health Organization 1978;56;5;811-3

Selected Publications

  • Optimal enzymes for amplifying sequencing libraries.

    Quail MA, Otto TD, Gu Y, Harris SR, Skelly TF, McQuillan JA, Swerdlow HP and Oyola SO

    Nature methods 2012;9;1;10-1

  • A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers.

    Quail MA, Smith M, Coupland P, Otto TD, Harris SR, Connor TR, Bertoni A, Swerdlow HP and Gu Y

    BMC genomics 2012;13;341

  • Improved protocols for the illumina genome analyzer sequencing system.

    Quail MA, Swerdlow H and Turner DJ

    Current protocols in human genetics / editorial board, Jonathan L. Haines ... [et al.] 2009;Chapter 18;Unit 18.2

  • A large genome center's improvements to the Illumina sequencing system.

    Quail MA, Kozarewa I, Smith F, Scally A, Stephens PJ, Durbin R, Swerdlow H and Turner DJ

    Nature methods 2008;5;12;1005-10

  • Accurate whole human genome sequencing using reversible terminator chemistry.

    Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J, Brown CG, Hall KP, Evers DJ, Barnes CL, Bignell HR, Boutell JM, Bryant J, Carter RJ, Keira Cheetham R, Cox AJ, Ellis DJ, Flatbush MR, Gormley NA, Humphray SJ, Irving LJ, Karbelashvili MS, Kirk SM, Li H, Liu X, Maisinger KS, Murray LJ, Obradovic B, Ost T, Parkinson ML, Pratt MR, Rasolonjatovo IM, Reed MT, Rigatti R, Rodighiero C, Ross MT, Sabot A, Sankar SV, Scally A, Schroth GP, Smith ME, Smith VP, Spiridou A, Torrance PE, Tzonev SS, Vermaas EH, Walter K, Wu X, Zhang L, Alam MD, Anastasi C, Aniebo IC, Bailey DM, Bancarz IR, Banerjee S, Barbour SG, Baybayan PA, Benoit VA, Benson KF, Bevis C, Black PJ, Boodhun A, Brennan JS, Bridgham JA, Brown RC, Brown AA, Buermann DH, Bundu AA, Burrows JC, Carter NP, Castillo N, Chiara E Catenazzi M, Chang S, Neil Cooley R, Crake NR, Dada OO, Diakoumakos KD, Dominguez-Fernandez B, Earnshaw DJ, Egbujor UC, Elmore DW, Etchin SS, Ewan MR, Fedurco M, Fraser LJ, Fuentes Fajardo KV, Scott Furey W, George D, Gietzen KJ, Goddard CP, Golda GS, Granieri PA, Green DE, Gustafson DL, Hansen NF, Harnish K, Haudenschild CD, Heyer NI, Hims MM, Ho JT, Horgan AM, Hoschler K, Hurwitz S, Ivanov DV, Johnson MQ, James T, Huw Jones TA, Kang GD, Kerelska TH, Kersey AD, Khrebtukova I, Kindwall AP, Kingsbury Z, Kokko-Gonzales PI, Kumar A, Laurent MA, Lawley CT, Lee SE, Lee X, Liao AK, Loch JA, Lok M, Luo S, Mammen RM, Martin JW, McCauley PG, McNitt P, Mehta P, Moon KW, Mullens JW, Newington T, Ning Z, Ling Ng B, Novo SM, O'Neill MJ, Osborne MA, Osnowski A, Ostadan O, Paraschos LL, Pickering L, Pike AC, Pike AC, Chris Pinkard D, Pliskin DP, Podhasky J, Quijano VJ, Raczy C, Rae VH, Rawlings SR, Chiva Rodriguez A, Roe PM, Rogers J, Rogert Bacigalupo MC, Romanov N, Romieu A, Roth RK, Rourke NJ, Ruediger ST, Rusman E, Sanches-Kuiper RM, Schenker MR, Seoane JM, Shaw RJ, Shiver MK, Short SW, Sizto NL, Sluis JP, Smith MA, Ernest Sohna Sohna J, Spence EJ, Stevens K, Sutton N, Szajkowski L, Tregidgo CL, Turcatti G, Vandevondele S, Verhovsky Y, Virk SM, Wakelin S, Walcott GC, Wang J, Worsley GJ, Yan J, Yau L, Zuerlein M, Rogers J, Mullikin JC, Hurles ME, McCooke NJ, West JS, Oaks FL, Lundberg PL, Klenerman D, Durbin R and Smith AJ

    Nature 2008;456;7218;53-9

  • Concentration of DNA in a flowing stream for high-sensitivity capillary electrophoresis.

    Park SR and Swerdlow H

    Analytical chemistry 2003;75;17;4467-74

  • Fully automated DNA reaction and analysis in a fluidic capillary instrument.

    Swerdlow H, Jones BJ and Wittwer CT

    Analytical chemistry 1997;69;5;848-55

  • Capillary gel electrophoresis for rapid, high resolution DNA sequencing.

    Swerdlow H and Gesteland R

    Nucleic acids research 1990;18;6;1415-9

[Wellcome Library, London]

Head of Research and Development

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