This proposal is in response to an RFA (NIG-85-HL-3B). In it we propose to examine by DNA technology the group of hemophiliacs with inhibitors who are already being studied immunologically by Dr. Howard Reisner (HL-32115). Dr. Reisner is assessing the patients for HLA haplotypes, Gm, helper:suppressor ratios, and inherited idiotypes (using batteries of monoclonal antibodies). We propose to complement his studies, in both hemophilia A and B, for both of which 3 DNA polymorphisms (RFLPs) have now been described. All subjects will be examined for DNA deletions. It is already known that deletions are related to inhibitors in hemophilia B. Those who do not have deletions will be haplotyped for appropriate polymorphisms. The controls will be a sample of hemophiliacs (of each type) without inhibitors, and a sample of normal individuals. They also will be examined for deletions and haplotyped. The hypothesis being tested by haplotyping is that the haplotypes of subjects with inhibitors are randomly distributed. If this hypothesis is rejected, we shall attempt to discover why certain haplotypes are disproportionately related to the development of inhibitors. The statistical correlations between Dr. Reisner's data and ours will be geared to testing the hypothesis that a set of unlinked factors, including DNA haplotypes, are related to the development of inhibitors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035152-03
Application #
3348784
Study Section
(SRC)
Project Start
1985-09-30
Project End
1990-09-29
Budget Start
1987-09-30
Budget End
1990-09-29
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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