Tom R. Gaunt, BSc, PhD

Lecturer in Bioinformatics and Molecular Genetics

Bristol Genetic Epidemiology Laboratories,
Dept. Social Medicine,
University of Bristol,
Oakfield House,
Oakfield Grove
Bristol BS8 2BN

 tom.gaunt@bristol.ac.uk

Current work

Cardiovascular disease (CVD) is a major cause of mortality in Great Britain. CVD and its risk factors of hypertension, diabetes and obesity are complex traits caused by multiple genetic and environmental components. A relationship is also observed between early growth and adult disease, suggesting that either foetal nutrition influences adult disease or that some genetic factors influence both early growth and adult disease.
In 2007 I was awarded a British Heart Foundation project grant (PG/07/131/24254) to genotype 50,000 single nucleotide polymorphisms in cardiovascular disease candidate genes (the Illumina/IBC "cardiochip") within the British Women's Heart and Health Study. This has led to a range of ongoing national and international collaborative projects on the genetic epidemiology of a range of cardiovascular and related phenotypes.
I also have active research interests in bioinformatics, computational biology and statistical genetics, and have developed programs for analysis of linkage disequilibrium and copy number variation. See http://apps.biocompute.org.uk/ for further details.

Previous work

We have previously published initial analyses of the relationship between genetic variation in the Growth Hormone/Placental Lactogen (GH/PL) gene cluster on chromosome 17 and both cardiovascular and metabolic phenotypes. I was awarded a British Heart Foundation Intermediate Fellowship in 2005 to complete comprehensive haplotype, gene copy number and association analyses of the genes within this region. This study gave an insight into the importance of this region in disease and contribute substantially to future research into therapeutic and diagnostic outcomes.
My previous work includes a comprehensive association analysis of the insulin-like growth factor (IGF2) gene and subsequent work on haplotype analyses of the TH-INS-IGF2 region of chromosome 11. This work demonstrated the importance of this region in the predisposition to weight gain in middle-aged men.
I have also been involved in a project on splicing of the insulin gene (INS) in which we demonstrated that the INS-HphI site, frequently used as a marker for the INS minisatellite, affects splicing of the gene.
Finally, I have been involved in a variety of methods development, including work on microplate array diagonal gel electrophoresis and SNP genotyping methodologies. I have also developed a number of software solutions to laboratory and informatic problems.

Funding

British Heart Foundation Project Grant PG/07/131/24254, 2007-10.
British Heart Foundation Intermediate Fellowship FS/05/065, 2005-8.

Publications

  1. Gaunt TR, Rodriguez S, Guthrie PA, Day IN. An expectation-maximization program for determining allelic spectrum from CNV data (CoNVEM): insights into population allelic architecture and its mutational history. Hum Mutat. 2010 Jan 14; [Epub ahead of print]
  2. Talmud PJ, Drenos F, Shah S, Shah T, Palmen J, Verzilli C, Gaunt TR, Pallas J, Lovering R, Li K, Casas JP, Sofat R, Kumari M, Rodriguez S, Johnson T, Newhouse SJ, Dominiczak A, Samani NJ, Caulfield M, Sever P, Stanton A, Shields DC, Padmanabhan S, Melander O, Hastie C, Delles C, Ebrahim S, Marmot MG, Smith GD, Lawlor DA, Munroe PB, Day IN, Kivimaki M, Whittaker J, Humphries SE, Hingorani AD; ASCOT investigators; NORDIL investigators; BRIGHT Consortium. Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. Am J Hum Genet. 2009 Nov;85(5):628-42.
  3. Dennison EM, Syddall HE, Jameson KA, Sayer AA, Gaunt TR, Rodriguez S, Day IN, Cooper C, Lips MA; Hertfordshire Cohort Study Group. A study of relationships between single nucleotide polymorphisms from the growth hormone-insulin-like growth factor axis and bone mass: the Hertfordshire cohort study. J Rheumatol. 2009 Jul;36(7):1520-6. Epub 2009 Jun 1.
  4. Rodriguez S, Gaunt TR, Day IN. Hardy-Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. Am J Epidemiol. 2009 Feb 15;169(4):505-14. Epub 2009 Jan 6.
  5. Lawlor DA, Harbord RM, Timpson NJ, Lowe GD, Rumley A, Gaunt TR, Baker I, Yarnell JW, Kivimaki M, Kumari M, Norman PE, Jamrozik K, Hankey GJ, Almeida OP, Flicker L, Warrington N, Marmot MG, Ben-Shlomo Y, Palmer LJ, Day IN, Ebrahim S, Smith GD. The association of C-reactive protein and CRP genotype with coronary heart disease: findings from five studies with 4,610 cases amongst 18,637 participants. PLoS One. 2008 Aug 20;3(8):e3011.
  6. Abdollahi MR, Huang S, Rodriguez S, Guthrie PA, Smith GD, Ebrahim S, Lawlor DA, Day IN, Gaunt TR. Homogeneous assay of rs4343, an ACE I/D proxy, and an analysis in the British Women's Heart and Health Study (BWHHS). Dis Markers. 2008;24(1):11-7.
  7. Gaunt TR, Rodriguez S, Day IN. Cubic exact solutions for the estimation of pairwise haplotype frequencies: implications for linkage disequilibrium analyses and a web tool 'CubeX'. BMC Bioinformatics. 2007 Nov 2;8:428.
  8. Publication Types: Comment Letter Rodriguez S, Gaunt TR, Vorechovsky I, Kralovicova J, Wood PJ, Day IN. Diabetes. 2007 Sep;56(9):e16; author reply e17.
  9. Rodriguez S, Gaunt TR, Day IN. Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease. Hum Genet. 2007 Aug;122(1):1-21. Epub 2007 May 30.
  10. Huang S, Chen XH, Payne JR, Pennell DJ, Gohlke P, Smith MJ, Day IN, Montgomery HE, Gaunt TR. Haplotype of growth hormone and angiotensin I-converting enzyme genes, serum angiotensin I-converting enzyme and ventricular growth: pathway inference in pharmacogenetics. Pharmacogenet Genomics. 2007 Apr;17(4):291-4.
  11. Lips MA, Syddall HE, Gaunt TR, Rodriguez S, Day IN, Cooper C, Dennison EM; Southampton Genetic Epidemiology Research Group. Interaction between birthweight and polymorphism in the calcium-sensing receptor gene in determination of adult bone mass: the Hertfordshire cohort study. J Rheumatol. 2007 Apr;34(4):769-75. Epub 2007 Feb 15.
  12. Abdollahi MR, Lewis RM, Gaunt TR, Cumming DV, Rodriguez S, Rose-Zerilli M, Collins AR, Syddall HE, Howell WM, Cooper C, Godfrey KM, Cameron IT, Day IN. Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome traits. Hum Mutat. 2007 Apr;28(4):365-73.
  13. Lawlor DA, Day IN, Gaunt TR, Hinks LJ, Timpson N, Ebrahim S, Davey Smith G. The association of the paraoxonase (PON1) Q192R polymorphism with depression in older women: findings from the British Women's Heart and Health Study. J Epidemiol Community Health. 2007 Jan;61(1):85-7.
  14. Zhang W, Maniatis N, Rodriguez S, Miller GJ, Day IN, Gaunt TR, Collins A, Morton NE. Refined association mapping for a quantitative trait: weight in the H19-IGF2-INS-TH region. Ann Hum Genet. 2006 Nov;70(Pt 6):848-56.
  15. Day IN, Rodriguez S, Kralovicova J, Wood PJ, Vorechovsky I, Gaunt TR. Questioning INS VNTR role in obesity and diabetes: subclasses tag IGF2-INS-TH haplotypes; and -23HphI as a STEP (splicing and translational efficiency polymorphism). Physiol Genomics. 2006 Dec 13;28(1):113. Epub 2006 Aug 1.
  16. Gaunt TR, Rodriguez S, Zapata C, Day IN. MIDAS: software for analysis and visualisation of interallelic disequilibrium between multiallelic markers. BMC Bioinformatics. 2006 Apr 27;7:227.
  17. Lawlor DA, Gaunt TR, Hinks LJ, Davey Smith G, Timpson N, Day IN, Ebrahim S. The association of the PON1 Q192R polymorphism with complications and outcomes of pregnancy: findings from the British Women's Heart and Health cohort study. Paediatr Perinat Epidemiol. 2006 May;20(3):244-50.
  18. Christensen MB, Lawlor DA, Gaunt TR, Howell WM, Davey Smith G, Ebrahim S, Day IN. Genotype of galectin 2 (LGALS2) is associated with insulin-glucose profile in the British Women's Heart and Health Study. Diabetologia. 2006 Apr;49(4):673-7. Epub 2006 Feb 9.
  19. Kralovicova J, Gaunt TR, Rodriguez S, Wood PJ, Day IN, Vorechovsky I. Variants in the human insulin gene that affect pre-mRNA splicing: is -23HphI a functional single nucleotide polymorphism at IDDM2? Diabetes. 2006 Jan;55(1):260-4.
  20. Rodriguez S, Huang S, Chen XH, Gaunt TR, Syddall HE, Gilg JA, Miller GJ, Cooper CC, Cook DG, Whincup PH, Day IN. A study of TH01 and IGF2-INS-TH haplotypes in relation to smoking initiation in three independent surveys. Pharmacogenet Genomics. 2006 Jan;16(1):15-23.
  21. Timpson NJ, Lawlor DA, Harbord RM, Gaunt TR, Day IN, Palmer LJ, Hattersley AT, Ebrahim S, Lowe GD, Rumley A, Davey Smith G. C-reactive protein and its role in metabolic syndrome: mendelian randomisation study. Lancet. 2005 Dec 3;366(9501):1954-9.
  22. Rodriguez S, Gaunt TR, Dennison E, Chen XH, Syddall HE, Phillips DI, Cooper C, Day IN. Replication of IGF2-INS-TH*5 haplotype effect on obesity in older men and study of related phenotypes. Eur J Hum Genet. 2006 Jan;14(1):109-16.
  23. Timpson NJ, Christensen M, Lawlor DA, Gaunt TR, Day IN, Ebrahim S, Davey Smith G. TAS2R38 (phenylthiocarbamide) haplotypes, coronary heart disease traits, and eating behavior in the British Women's Heart and Health Study. Am J Clin Nutr. 2005 May;81(5):1005-11.
  24. Abdollahi MR, Gaunt TR, Syddall HE, Cooper C, Phillips DI, Ye S, Day IN. Angiotensin II type I receptor gene polymorphism: anthropometric and metabolic syndrome traits. J Med Genet. 2005 May;42(5):396-401.
  25. Day IN, Chen XH, Gaunt TR, King TH, Voropanov A, Ye S, Rodriguez S, Syddall HE, Sayer AA, Dennison EM, Tabassum F, Barker DJ, Cooper C, Phillips DI. Late life metabolic syndrome, early growth, and common polymorphism in the growth hormone and placental lactogen gene cluster. J Clin Endocrinol Metab. 2004 Nov;89(11):5569-76.
  26. Lawlor DA, Day IN, Gaunt TR, Hinks LJ, Briggs PJ, Kiessling M, Timpson N, Smith GD, Ebrahim S. The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis. BMC Genet. 2004 Jun 23;5:17.
  27. Rodriguez S, Gaunt TR, O'Dell SD, Chen XH, Gu D, Hawe E, Miller GJ, Humphries SE, Day IN. Haplotypic analyses of the IGF2-INS-TH gene cluster in relation to cardiovascular risk traits. Hum Mol Genet. 2004 Apr 1;13(7):715-25. Epub 2004 Jan 28.
  28. Gaunt TR, Hinks LJ, Rassoulian H, Day IN. Manual 768 or 384 well microplate gel 'dry' electrophoresis for PCR checking and SNP genotyping. Nucleic Acids Res. 2003 May 1;31(9):e48.
  29. O'Dell SD, Syddall HE, Sayer AA, Cooper C, Fall CH, Dennison EM, Phillips DI, Gaunt TR, Briggs PJ, Day IN. Null mutation in human ciliary neurotrophic factor gene confers higher body mass index in males. Eur J Hum Genet. 2002 Nov;10(11):749-52.
  30. Gaunt TR, Cooper JA, Miller GJ, Day IN, O'Dell SD. Positive associations between single nucleotide polymorphisms in the IGF2 gene region and body mass index in adult males. Hum Mol Genet. 2001 Jul 1;10(14):1491-501.
  31. Holloway JW, Lonjou C, Beghe B, Peng Q, Gaunt TR, Gomes I, Hall IP, Dewar JC, Wilkinson J, Thomas NS, Holgate ST, Morton NE. Linkage analysis of the 5q31-33 candidate region for asthma in 240 UK families. Genes Immun. 2001 Feb;2(1):20-4.
  32. O'Dell SD, Gaunt TR, Day IN. SNP genotyping by combination of 192-well MADGE, ARMS and computerized gel image analysis. Biotechniques. 2000 Sep;29(3):500-4, 505-6.