The EDs are a heterogeneous collection of disorders of unknown pathogenesis. The need to develop new molecular approaches to their analysis has been noted, and the investigators believe that molecular genetic studies, specifically linkage analysis, will improve their classification, produce new diagnostic tools, and ultimately lead to identification of their molecular defects and to an understanding of the process of normal morphogenesis. The investigators propose to study two prototypic disorders, XLHED, the commonest of the EDs, and the Clouston syndrome, an hidrotic form of ED which is inherited as an autosomal dominant trait. For XLHED: The investigators will perform fine genetic mapping studies of the disorder, localized to Xp11.1-Xq21.1 region, to define the order of closely linked polymorphic marker loci in relation to the disease locus. The identification of close flanking markers is essential for both accurate diagnostic applications, and for the physical mapping and cloning of the XLHED locus. To this end, the investigators will screen for highly polymorphic (heterozygosity >70 percent) microsatellite DNA markers in the pericentromeric region of the X-chromosome. The investigators will utilize these markers to address the question of the existence and frequency of a proposed clinically indistinguishable autosomal recessive form of the disorder, which if unrecognized could cause serious diagnostic errors. In addition, a large number of unrelated males will be screened, initially with anonymous DNA probes, but ultimately with expressed and conserved sequences from the region, to identify sub-microscopic deletions involving the XLHED locus. For the Clouston syndrome: Its position on the human gene map, presently unknown, will be localized by the linkage analysis of two very large kindreds, utilizing a series of highly polymorphic loci (RFLPs and microsatellites) distributed over all autosomes (exclusion mapping). Potential candidate genes or chromosomal regions will be given priority. Once linkage is established, fine mapping will be performed, to lay the groundwork for subsequent physical mapping around the disease locus, and cloning of the gene.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR040741-01A1
Application #
3161211
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1991-07-01
Project End
1994-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Schools of Medicine
DUNS #
009584210
City
Portland
State
OR
Country
United States
Zip Code
97239