- Ex: 54005
Weldon Professor of Computational and Statistical Genetics
Genetics, Evolution & Environment
Div of Biosciences
I have worked on many aspects of bioinformatics and statistical genetics, but most of my research since 2000 has concerned the statistical genetic analysis of populations descended from multiple inbred founders. These include rodents and plants. The chromosomes of individuals from such populations are mosaics of the founders, and this observation can be used to investigate numerous questions about the genetic architecture of complex traits. These centre around determining precisely how a genetic variation at a locus is associated with a phenotype - for example whether it is caused by a single variant of by multiple linked variants (Baud et al 2013 Nat Genet), and whether the parent-of-origin of an allele modulates its phenotypic effect (Mott et al 2015 Cell). To do this, I developed an analysis framework based on decomposing the genomes of individuals into probabilistic mosaics of the population founders (Mott et al 2000, PNAS, Yalcin et al 2005 Genetics, Durrant et al 2010 Genetics). With collaborators, I have developed genetic reference populations descended from sets founders, that are ideal for genetic analysis using this framework. These include the Collaborative Cross mouse reference population (Durrrant et al 2011 Genome Research, Aylor et al 2011 Genome Research) and the Arabidopsis thaliana MAGIC lines(Kover et al 2009 PLoS Genetics). I have also applied these methods to the study of quantitative genetics in heterogeneous stock mice (Valdar et al 2006 Nature Genetics) and heterogeneous stock rats (Baud et al 2013 Nature Genetics). I collaborated in the sequencing of the founder genomes of these populations (Keane et al 2011 Nature, Gan et al 2011 Nature). I have also used these methods to dissect the genetic architecture of parent-of-origin effects (Mott et al 2014 Cell). In human genetics, and in collaboration with the CONVERGE consortium I helped analyse human case-control data leading to the first replicated discovery of loci associated with major depressive disorder (Na et al 2015 Nature), and the link between mitochondria and depression (Na et al 2015 Current Biology). My current research activities include an analysis of structural variation based on treating structural variants as quantitative traits (Imprialou et al 2017, Genetics). I have two BBSRC research grants analysing MAGIC populations of wheat, chickpea and rice.