Research objectives and content
The research objectives are two-fold:
1. To conduct genetic and physical mapping in the 7q36 region in DNA samples from patients and families with autosomal dominant sacral agenesis. This disorder was first localised to the 7q36 region last year by Professor Strachan's group, and the critical region containing the gene is still several Mb long I plan to conduct further mapping in these families in order to help narrow the location of the gene, and thereby facilitate future positional cloning/positional candidate gene approaches to identify the gene.
2. To isolate and characterise novel genes in the Darier's disease region at 12q24.1.
This disorder was simultaneously mapped by Professor Strachan's group and a group from Cardiff in 1993. Since then Professor Strachan has been able to narrow the location of the gene to an interval of about 2Mb which appears to be gene-rich and which contains unidentified genes for some other disorders, notably spino- cerebellar ataxia type 2. I plan to identify novel genes in this region by comparative mapping between human and pufferfish, to characterise selected genes and in promising cases, test for patient-specific mutations.
Training content (objective, benefit and expected impact)
The project is intended to provide a comprehensive training in human gene mapping and gene identification. The autosomal dominant sacral agenesis project is designed to provide experience of basic genetic and physical mapping whereas the Darier's disease component will provide expertise in more advanced technologies based on identifying and characterising genes in cosmids and PAC clones. In addition to providing a wealth of valuable expertise in human molecular genetics, the host institution offers excellent research facilities and equipment and an excellent academic environment. The project may lead to identification of medically important genes and the training is important for my personal scientific development.
Links with industry / industrial relevance (22)
Although industrial links are not envisaged immediately, identification and characterisation of some novel genes may suggest a gene function that could stimulate collaborative links with industrial partners.