Asthma Clinical Trial
To identify gene variants in human chromosome 5Q31-33 that may be involved in the pathogenesis of asthma.
BACKGROUND:
Markers and genes in chromosomal region 5q31-33 have been shown to be linked or associated
to asthma or components of the asthma phenotype, suggesting that this chromosomal region is
important in the genetic susceptibility to asthma, yet it has been difficult to show that a
specific gene in this region plays a major role in asthma development or progression. Some
of this difficulty arises from the fact that many genes are likely to be involved in the
pathogenesis of asthma, with no single gene having an effect that will emerge as a major
contributor, as well as the fact that the strong influence of environmental factors will
complicate the analyses. Having recognized these issues, the investigators will use
components of the asthma-associated phenotype, including eosinophilia and a compound "atopy"
phenotype, to identify relevant asthma-related genes in this region. The identification of
the genes and their genetic variants that may be associated with asthma and its related
phenotypes may provide important new information on the pathogenesis of asthma.
The study is in response to a Request for Applications on "Positional Candidate Approaches
in Asthma Gene Discovery" released in October 1999.
DESIGN NARRATIVE:
Dr. Martinez and his group have found linkage between markers in chromosome 5q31 and both
eosinophilia and a composite 'atopy' phenotype. The goal of the study is to identify the
gene variants in 5q31-33 that are responsible for these two linkage signals. This will be
done using the same population of families enrolled in the Tucson Children's Respiratory
Study that have now been followed since the time of birth of the index child approximately
18 years ago. In the first specific aim, gene variants having a frequency of 2% or more in a
group of 25 known genes in chromosome 5q will be identified. The 25 genes have been selected
among those that have been mapped to the 28 cM interval that was tested for linkage in
previous studies. The second specific aim is to perform linkage disequilibrium mapping using
100 known polymorphisms in the region of approximately 6.4 cM that shows the highest
likelihood of containing the gene variants responsible for either or both of the
eosinophilia and atopy linkage signals. Detailed local mapping using both published and
newly discovered polymorphisms in and around the areas of positive signals will also be
performed. Based on the previous experience of these investigators for the same chromosomal
region, several association/linkage signals in chromosome 5q are expected to be found.
The study completion date listed in this record was obtained from the "End Date" entered in
the Protocol Registration and Results System (PRS) record.
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