SUMMARY OF RESEARCH BEING UNDERTAKEN

Epidermolysis Bullosa is a set of genetically inherited skin blistering conditions affecting 1 in 17,000 of the population. The various forms of EB Simplex are the most common with an estimated 2000 sufferers in the UK alone. The research group in Dundee led by Prof Lane are world leaders in EB Simplex research. Other projects are being funded by Cadbury & Wellcome. In 1997 DebRA also received a grant for a Gene Sequencer for use by this group. Their research indicates that there are many different mutations which need to be determined in each individual case.

Keratins are filamentous proteins which are found in a number of tissues including the skin. They form a network throughout the cell and are important for its structural integrity. Defective keratin filaments make cells more fragile and less resilient to mechanical stress. This occurs in Epidermolysis Bullosa Simplex (EBS). The aim of this project is to identify mutations in keratins and associated proteins which cause EBS. A direct and practical consequence of this research is that once a mutation has been found it is possible to perform DNA-based prenatal diagnosis at around eleven weeks gestation. In addition, information on the molecular nature of such mutations will lead to a better understanding of the EBS which is important for the development of treatments for the disease. If or when gene therapy is developed for EBS, it is likely that a prerequisite will be the identification of the underlying genetic defect in each family.

The AB1377 automated DNA sequencer, purchased in 1997 through a grant from the UK National Lottery Charities Board to DebRA, is central to this research and has greatly increased the throughput of samples and mutation detection rate. The result is the generation of large amounts of data which have to be analysed and catalogued. The DNA Sequencer has a dedicated computer but this can only be used for further data analysis when the sequencer is not operating. The intention is to run the sequencer close to maximum capacity, so a major limiting factor is the rate at which data can be analysed. In addition there are running costs to cover the costs of the synthesis of oligonucleotide primers and the reagents required for linkage analysis, DNA sequencing and polymorphism analysis.