ECTODERMAL DYSPLASIAS A MOLECULAR GENETIC ANALYSIS

Project: Research project

Description

DESCRIPTION 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.
StatusFinished
Effective start/end date7/1/916/30/94

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Ectodermal Dysplasia
Molecular Biology
Research Personnel
Genes
Sweating
DNA Probes
X Chromosome
Diagnostic Errors
Genetic Markers
Morphogenesis
Restriction Fragment Length Polymorphisms
Microsatellite Repeats
Organism Cloning

ASJC

  • Medicine(all)