| SUMMARY OF RESEARCH BEING UNDERTAKEN
Aims of Research
i. To establish a genome-wide semi-automated genotyping strategy
based on fluorescent multiplex PCR microsatellite markers for rapid genome analysis of
"new" forms of EB and similar skin fragility diseases.
ii. To identify the genetic locus for LOC syndrome using the above
strategy.
iii. Identify the gene containing pathogenic mutations responsible
for LOC syndrome by (a) analysis of candidate genes and/or expressed sequence tags which
map within the disease interval; or (b) positional cloning techniques.
Background
The Epithelial Genetics Group, a separate entity within the
Department of Dermatology and Cutaneous Biology, Jefferson Medical College, was
established at the end of 1996 with the recruitment of Irwin McLean and Frances Smith,
formerly researchers in Prof. Birgit Lane's laboratory, Cell Structure Research Group,
University of Dundee, UK. A principal aim of the Epithelial Genetics Group is to
investigate Epidermolysis Bullosa and
related diseases causing fragility of the skin and other epithelial
tissues. There exists a well established collaboration between Dr McLean and Dr John
McGrath at St Thomas' Hospital, London in relation to the study of EB both in terms of
ultrastructure and molecular genetics.
Over the past 5 years, members of this group (McLean, McGrath) have
been involved in the study of EB and similar genetic skin disorders. This work arose out
of the joint discovery by that group that mutations in human keratin genes are responsible
for the autosomal dominant disorder, Epidermolyis Bullosa Simplex (EBS). Following this
discovery, they went on to study the molecular pathogenesis of a number of other forms of
EB and related keratinizing disorders. These findings have enabled facilitated greatly
improved genetic counselling and pre-natal diagnosis of EB and similar diseases.
Summary
The proposed project will help diagnosis and classification of EB.
This basic knowledge is necessary for the design of EB therapy.
There are now 10 genes known to cause EB. Identification of these
genes has allowed better diagnosis for the various forms of EB. Also, carriers of the
faulty gene can be identified in affected families and pre-natal testing can be offered
couples carrying these gene defects. In this way, this distressing disorder can be
prevented from occurring again in affected families. However, there are many forms of EB
where the gene is still unknown and these families cannot be offered genetic counselling
until the genes are found. Until recently, finding new genes has been very difficult and
expensive and could take one or two years. However, recent advances in genetics have led
to the development of a new system for finding genes in weeks instead of years and is much
less expensive. This project seeks to set up a system dedicated to looking for EB genes.
The researchers will first use the system to find the gene for LOC syndrome, a severe type
of EB and then go on to look at other similar diseases. The system will be made freely
available to other EB researchers around the world. In the long term, knowing what all the
EB genes are will help us understand the function of the skin and design gene therapy for
EB. |
