WTCHG: About

About the Wellcome Trust Centre for Human Genetics

Introduction

The Wellcome Trust Centre for Human Genetics (WTCHG) undertakes research into the genetic basis of multifactorial diseases such as hypertension, diabetes, heart disease, infectious diseases, psychiatric disorders and multiple sclerosis. The WTCHG is part of the University of Oxford's Division of Medical Sciences, with access to large patient collections and the Division’s considerable strengths in complex disease mapping. The WTCHG currently has approximately 400 scientific researchers and holds grants with an overall value of approximately £60 million and has an annual turnover of around £11 million, of which £10 million is for research.

The WTCHG is organised as a confederation of independent grant-funded laboratories, each focused on particular disease areas, together with four centrally-funded core facilities: genomics, molecular cytogenetics and microscopy, bioinformatics/statistical genetics and transgenics.

History

The WTCHG was opened in June 1994 and was originally located in temporary premises at the Nuffield Orthopaedic Centre, where the research programme was rapidly developed using large scale semi-automated genotyping supported by robotics. The WTCHG grew quickly with over 180 research scientists in 1998 and served as a focal point for genetic mapping in multifactorial diseases in the UK. In June 1999 the WTCHG moved to a new purpose-built facility, The Henry Wellcome Building of Genomic Medicine, located on the Institute of Health Sciences Campus in Oxford. The new Centre is designed to provide permanent space for the WTCHG and to allow expansion of the scientific programmes to incorporate complementary research activities in structural biology and functional genomics. This location will greatly facilitate interactions between the genetics group and those in the population epidemiology programmes in Oxford housed at the Institute of Health Sciences and the newly constructed Richard Doll Building for trials and epidemiology.

Scientific achievement

Multifactorial diseases are caused by variants in multiple genes interacting with each other and in combination with environmental factors to increase the susceptibility to disease. Identifying and characterising the genes involved in these disorders is a difficult task because of the reliance on substantial resources such as large collections of case control and family data, highly informative genetic markers which span the genome, and statistical approaches specifically developed to deal with multifactorial disease.

The scientific programme within the Centre has developed substantially since its inception. The large-scale genotyping capacity of the Centre has allowed us to achieve rapid success in identifying verified linkages and associations for disease susceptibility genes. Fine mapping has reduced many linkages to focus on specific candidate genes using linkage disequilibrium mapping. Disease genes have been identified and characterised in diabetes, neurodevelopmental disorders, infectious diseases and asthma.

The future

The Centre is focusing on three main disease areas in its genetics research programme; neurogenetics, genetics of inflammation and immunity, and the genetics of cardiovascular disease/metabolic syndrome. The Centre will retain disease gene mapping and identification as its core activity and has already evolved its strategy to incorporate large-scale single nucleotide polymorphism (SNP) association strategies. In order to capitalise on newly available SNP and haplotype resources, the Centre is active in national and international collaborations with large epidemiology groups with expertise in large patient cohorts. This unique access to epidemiological material should provide ample patient and control populations for future SNP studies.

It has become clear from the field internationally that using a genetics approach alone does not permit a candidate disease gene variant to be proven as giving rise to susceptibility to common disease. In order to achieve the scientific objectives of the Centre, such gene variants must be studied in their physiological, structural and functional context. Only with both a genetic and functional strategy can we understand the biological pathways that have been implicated in common disease. Therefore, in the new building, we have assembled internationally strong groups in structural biology (Stuart, Jones, Fuller) who are leading the adjacent MRC-funded Oxford Protein Production Facility and newly constructed Facility for the Evaluation of Infectious Particles. In addition we have continued to foster our programmes in the functional analysis of disease genes and their variants relevant to the genetics focus of the Centre (Watkins, Ratcliffe, Pugh, Kwiatkowski, Monaco, Fisher) and models of human disease and development (Watkins, Bhattacharya,). In the newly constructed Henry Wellcome Laboratory for Genomic Medicine (laboratory 4) we have initiated a strong programme in cell and developmental biology with the research programmes of E Robertson and E Bikoff. These programmes should be the nucleus for additional functional genomics and developmental biology groups to be recruited in The Henry Wellcome Laboratory for Genomic Medicine within the next few years.