Research Theme within School of Biosciences: Molecular and Cell Biology
My research field is in Quantitative and Population Genetics, with major research interests in understanding the genetic architectures and mechanisms that underlie quantitative genetic variations, using both theoretical and experimental approaches. Our recent projects include:
Development of theoretical and experimental strategies for dissecting complex traits
Dissection of polygenic variation at molecular level has been a long standing target in classical genetics but still a challenging task in modern genomics. Although the last two decades have witnessed the dominance of research on mapping quantitative trait loci (QTL) in man, animal and plant species, the mapping precision and resolution that leads itself to molecular cloning of the target genes has remained a rare event. This project develops theoretical approaches for mapping and identifying the major effect genes that contribute to phenotypic variation of polygenic traits through altered coding sequence or expression of the genes. We have established an experimental model with budding yeast (S. cerevisiae) to dissect genic and transcriptional regulation network that affects natural variation in ethanol tolerance through integrating genomic, transcripteomic and proteomic information.
Theoretical modeling and prediction of marker-QTL linkage disequilibrium in natural populations
Association study has proven to be a powerful approach to isolate the oligo-genic basis of inherited diseases in humans and many other inherited characters in animal/plant species which segregate according to simple Mendelian rules. To extend the basic principle to complex traits, where the underlying genotype is no longer inferable directly from the corresponding phenotype, we are developing statistical approaches for modelling and predicting linkage disequilibria between genetic marker loci and loci affecting a complex trait in populations with various genetic structures.
Theory and methods for reconstructing genetic linkage maps in autotetraploid species
Construction of genetic linkage maps is usually the first milestone in launching a genome project for an organism. In the era of genomics, genetic linkage maps are now available or quickly becoming available in humans and in almost all important animal and plant species. In sharp contrast, the corresponding study in polyploid species is theoretically challenging and still in its infancy. Our research on this topic focuses on developing theory and statistical approaches for genetic map construction and for modelling population genetic data in autotetraploid species, an example of which is cultivated potato, the world fourth most important food crop and the world food of future.
Evolutionary comparative genomics
Taking advantage of rapidly accumulating databases of genome studies and the datasets collected from our own experiments, we investigate the process and molecular mechanisms driving the divergent evolution of duplicate genes in the yeast protein-protein interaction network, the evolution of enzymatic genes in the yeast metabolic network, and the expression divergence between duplicate genes in the yeast genome.
Molecular aetiology of human inherited diseases
Working with our collaborators in Fudan University (Shanghai, China), we carried out experimental analyses to understand the molecular and/or cellular bases for non-small cell lung cancer (NSCLC), partial androgen receptor insensitivity syndrome and non-tuberculosis mycobacterium infection. Armed with these skills and our theoretical power, we are now able to study quantitative traits on the basis of integrating these powers.