Medical and molecular genetics

Cross-cutting discipline leads: Professor Chris Mathew and Professor Ellen Solomon

The challenge

Many hundreds of genetics disorders exist which arise from mutations in a single gene, eg cystic fibrosis, Huntington's disease, and familial breast cancer.  The genes for most of the more common genetic disorders have been identified, and accurate diagnostic tests are now available.  However, the genes responsible for many rare single gene disorders are unknown.  Identifying these is a basis for diagnosis and the development of future therapies.

It is now clear that most common disorders such as diabetes and cancer develop from a combination of genetic susceptibility and environmental effects.  Identification of the genes involved will provide clues to the pathogenesis, and is likely to lead to improved diagnosis, disease classification, presymptomatic screening and the development of therapies targeted at the relevant pathways.

Our goals

• To identify biomarkers which can be used in the clinic to diagnose and screen for both single gene disorders and common disorders where genes play a role in susceptibility
• To identify new therapeutic targets for treatments

Our research

We are focused on:

• Finding genes for rare, serious genetic disorders by sequencing all the coding regions of all known genes (whole exomes)
• Finding epigenetic mutations in developmental disorders
• Finding genes for inflammatory diseases - Crohn's disease, ulcerative colitis, psoriasis and severe acne - by genome-wide association scans, high throughput sequencing of genetically associated regions and whole-exome sequencing in familial forms of these disorders
• Translating genetic findings into biomarkers for early detection and diagnosis of these disorders.  For example:

• Development of a psoriasis transcriptome signature correlated with underlying genetic profile, disease phenotype and therapeutic response 
• Use of genetic and serum biomarkers for presymptomatic screening of first degree relatives of patients with Crohn's disease

• Finding genetic mutations that drive the development of some cancers by high throughput sequencing of paired samples of germline DNA and tumour material in therapy-related acute myeloid leukaemia and oesophageal cancer

Our interdisciplinary programmes

We lead one of the BRC's interdisciplinary research programmes:

• Search for genetic clues to better predict complex diseases

We are also involved in a number of other interdisciplinary programmes:

• Extending understanding of arterial disease
• Environment and respiratory health
• Biomarker-led individualisation of therapy in organ transplantation

Publications

Recent publications include:

Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium 2, Strange A, Trembath RC et al.  A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1.   Nat Genet. 2010 Nov;42(11):985-90. Epub 2010 Oct 17.

UK IBD Genetics Consortium WellcomeTrust Case Control Consortium 2, Lees CW, Prescott NJ, et al. Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nat Genet. 2009 Dec;41(12):1330-4

Prescott NJ, Dominy KM, Kubo M, Lewis CM, Fisher Sa, Redon R, Huang N, Stranger BE, Blaszczyk K, Hudspith B, Parkes G, Hosono N, Yamazaki K, Onnie CM, Forbes A, Dermitzakis ET, Nakamura Y, Mansfield JC, Sanderson J, Hurles ME, Roberts RG, Mathew CG. Independent and population-specific association of risk variants at the IRGM locus with Crohn's disease. Human Molecular Genetics 2010 Jan:19 (9):1828-1839.

Who we are

Guy's Hospital is home to the South East Thames Genetics Service, and offers a full diagnostic, genetic counselling, and genetic testing service to individuals and families affected with genetic disorders. This service is underpinned by three laboratories (DNA diagnostics, cytogenetics laboratory and biochemical genetics).

Genetics research is an important part of King's Health Partners Academic Health Sciences Centre.

Contact us

Dr Amanda Lindsay PhD
BRC Resource Manager: Genetics cross-cutting discipline
Email: Amanda.lindsay@gstt.nhs.uk
Phone: 020 7188 4829