Genetics, Evolution & Environment
Div of Biosciences
Since finishing my PhD I have worked to develop and apply mathematical/statistical/computational methods and ideas in genetics. I have contributed to aspects of population, evolutionary, medical and forensic genetics.
In forensic genetics, my principal contribution has been to develop methods to allow for coancestry effects in the interpretation of DNA profiles. Match probability formulae incorporating coancestry coefficients are often called the "Balding-Nichols formulae" following our 1994 paper. More recently I have developed methods for the interpretation of low template DNA profile evidence, initially in collaboration with John Buckleton of ESR New Zealand (2009 paper).
The forensic match formulae are based on the multinomial-Dirichlet distribution, which I developed and applied to subpopulation allele counts. This led to the first satisfactory definition of the coancestry coefficient (Fst, or theta), and a likelihood-based approach to its estimation. Embedding this distribution in a hierarchical model allowing for subpopulation and locus effects, Mark Beaumont and I in our 2004 paper developed a widely-used approach for detecting loci subject to selection (evidenced by unusually high or low variation across subpopulations). The beta-binomial (or more generally multinomial-Dirichlet) as a distribution for simulating subpopulation allele frequencies is sometimes called the "Balding-Nichols model" following our 1995 paper.
Mark and I, with Wenyang Zhang, wrote in 2002 a foundational paper in the field of Approximate Bayesian Computation (ABC). We introduced a local linear regression adjustment which has proved very useful, but perhaps just as important we provided the first useful review of the method, that had been developed in stages by earlier authors, and promoted it as a powerful and flexible statistical technique.
With Ian Wilson, I developed one of the first successful softwares (Batwing) for modelling the demographic history of populations based on explicit modelling of the genetic ancestries of individuals sampled from the populations (1998 and 2003 papers). It has been widely used, particularly to model paternal lineages from Y-chromosome data.
I've written or co-authored a number of review papers that have proved popular, on statistical methods for genetic association studies (2006), on Bayesian methods and on population structure and cryptic relatedness in genetic association (both 2009) and on genome-wide epigenetic studies (2011). Will Astle, working with me, developed a fast algorithm for mixed model analysis of genetic association studies, described in our 2009 review and available within the MixAbel section of the GenAbel R software.
Currently I continue my established pattern of very wide ranging applications of statistics in genetics. I am involved in projects on statistical methods for pharmacogenetics, including genetic covariates in pharmacokinetic models, sequencing for rare variants in inherited cardiac conditions, genomic selection in crops and breed identification in mixed-breed dogs. I also remain active in statistical methods for forensic DNA profiles.
I received a Higher School Certificate (NSW, Australia) in 1978, after studies at Chevalier College Bowral (1973 - 76) and Kiama High Shool (1977 - 78). I gained a total score of 444/500 in subjects: Mathematics (4 unit), Physics (2 u), Chemistry (2 u), English (2 u), and French (2 u). My best subject was mathematics (189/200), so I decided that I may as well stick with what I was good at and continued studying that at University, after a year travelling in Europe, including a stint as a road-worker in France. To save up for the trip I did office work in an insurance company in North Sydney, which I left for higher pay as a cleaner at the NSW Government stores (in Alexandria, Sydney, but fortunately now demolished).
My undergraduate degree was a 1st class honours in Mathematics, with University Medal, from the University of Newcastle (Aust.). I studied there from 1980 to 83. Summer vacations were spent doing shift work at the Port Kembla steel works, modelling water consumption at the Newcastle water utility, and health statistics research assistance - in heart disease risk factors, with Annette Dobson and Bob Gibberd. My honours project developed a mathematical model of tumour-induced neovascularisation, supervised by Sean McElwain. We published a paper in JTB in 1985.
During 1984 I held various part-time tutoring and research assistant positions at Newcastle, some with the Hunter Health Statistics Unit.
In January 1985 I left for England, to study for a PhD in Mathematics at Oxford, which I was awarded in 1989. My supervisor was initially John Hammersley but after a few months I switched to Peter Clifford. My thesis, entitled "On some annihilating particle systems", involved stochastic processes and was motivated by problems in physical chemistry (guided by collaborator Nick Green). My college was Trinity, where I also did some tutoring work and was Junior Dean for 2 years.
During 1988-89, while finishing my PhD, I was Junior Lecturer in Mathematical Statistics at Oxford, the first appointment in the newly-created Department of Statistics, and also Lecturer in Mathematics at Lady Margaret Hall.
In October 1989 I started my first permanent position as Lecturer in Probability & Statistics at Queen Mary & Westfield College London, a position associated with Peter Donnelly's new chair. In 1995 I was promoted to Senior Lecturer, and in 1995 - 96 I had a sabbatical year at U Chicago (4 months; Peter Donnelly had just moved there), USC Los Angeles (2 months) and UNSW Sydney (6 months).
In January 1997 I started as Professor of Statistical Genetics in the Department of Applied Statistics at Reading, a position created by the recent retirement of Robert Curnow. A lectureship connected with that position was awarded to John Whittaker, and we collaborated over many subsequent years.
In September 2001 both John and I moved to Imperial College London, in the Department of Epidemiology and Public Health at the St Mary's Hospital campus, Paddington. I left Imperial to move to the UGI in September 2009. Vincent Plagnol arrived at the UGI at the same time to take up a lectureship.