Research Projects
Analysis of complex traits in relation to Mouse models of human disease (with Prof Jonathan Flint)
(i) Analysis of QTL Networks.
I hold a Wellcome Trust Programme Grant with Prof Jonathan Flint to investigate gene networks in The main focus of our research is the analysis of a rich dataset of phenotypes, genotypes and gene expression measured in a population of 2000 heterogeneous stock mice (Mott et al 2000, PNAS; Valdar et al 2006, Nature Genetics; Solberg et al 2006 Mammalian Genome; Valdar et al 2006 Genetics; Huang et al 2009 Genome Research). We are currently mining these data to investigate the relationship between gene co-expression networks in hippocampus, liver and lung and the quantitative trait loci we have mapped for over 100 phenotypes.
Key people associated with this project are Dr William Valdar (funded by a grant from the European Union Framework 6 Programme, contract number LHSG-CT-2003-
503265 and by the Medical Research Council, UK) and Dr Caroline Durrant (funded by the Medical Research Council, UK), Dr Wei Yuan and Dr Marko Oliynyk (both Wellcome-funded)
(ii) The Collaborative Cross (with Dr Fuad Iraqi, Tel Aviv University Israel)
I hold Wellcome Trust grants to generate a new population of approximately 100 recombinant inbred lines of mice descended from eight diverse inbred strains (Iraqi at el, 2008 Mammalian Genome). These lines, once completed, will form part of the Collaborative Cross, an international programme to generate a genetic reference panel for systems genetics. The breeding work is carried out at Tel Aviv University by Dr Fuad Iraqi. Currently the lines are about 80% inbred and are scheduled to be completed by 2012.
Complex Trait Analysis in Arabidopsis thaliana
From a statistical genetics perspective, the model plant A thaliana has many similarities with the mouse. Both can form genetically stable inbred strains and can be crossed to generate complex populations which are ideal for mapping quantitative traits. Many of the analytical techniques our group have developed are applicable to both systems. One advantage of working with A thaliana (apart from its intrinsic importance as a model plant) is that it is possible to make recombinant inbred lines very quickly in comparison with the mouse, and therefore to generate genetic reference panels and devise and test statistical methods, and then apply the lessons learnt to the mouse.
With Dr Paula Kover (University of Manchester) we have developed a genetic reference panel of over 500 recombinant inbred lines of A thaliana, descended from 19 genetically diverse inbred founder accessions (Kover et al, 2009 submitted). This work is funded by the BBSRC.
I hold a BBSRC grant to resequence the genomes of the founders using Illumina GAII short-read sequencing. The compact size of the reference genome (120 Mb) means it is possible to generate high coverage easily in comparison to the mouse. We are developing algorithms to assemble the reads (with Dr Xiangchao Gan) and will make the data available in 2009. Using this data we can impute the genome of each recombinant inbred line (which is a mosaic of the 19 founders) in order to perform high-resolution genetic association.
Other Projects
For other projects underway in this group, please see the Group Member pages.