Genetical genomics and molecular phenotyping

Finding genes that increase risk of disease is only a first step in understanding the causes of disease. To ultimately find better methods for diagnosis and treatment, we need to understand how genes act through complex biological mechanisms. Various technologies are available now to measure levels of molecules produced by genes, such as proteins, peptides, and lipids. Our group is studying how measurements of such ‘down-stream gene products’ relate to both genes and the disease of interest, how they can be incorporated in large-scale epidemiological studies, and – ultimately – how they can be used to find biomarkers for disease and surrogate markers for treatment effectiveness studies.

We are involved in molecular phenotype variability studies part of the EU-funded MolPAGE programme Together with the Dept of Statistics at Oxford (Prof Chris Holmes), and the Dept of Twin Research & Genetic Epidemiology at King’s College, London (Prof Tim Spector), our group leads the investigation of biological and experimental variability of data in 60 female twin pairs derived from a variety of molecular phenotyping platforms, including: gene expression transcriptomics; mass-spectrometry and microarray-based proteomics; and mass-spectrometry and NMR-based metabonomics.

In a separate study of 299 female twins, in collaboration with the Dept of Twin Research & Genetic Epidemiology at King’s College (Prof Tim Spector) and Dr Lon Cardon at GSK Ltd, we are investigating the potential to utilise gene expression information in lymphoblastoid cell lines to find associations between clinical phenotypes and genetic variants. Our group is also collaborating on a larger follow-up study in multiple tissues – the MUTHER (MUltiple Tissue Human Expression Resource) Project – coordinated by Prof Tim Spector, Prof Mark McCarthy (OCDEM, Oxford), Dr Panos Deloukas and Dr Manolis Dermitzakis (Wellcome Trust Sanger Institute).