The overall goal of this research proposal is to delineate the cis control of the globin gene switching and the structure function relationships in the beta-locus control region (LCR). There are six specific aims with a number of subsidiary aims which include: 1) To develop new methodologies for using yeast artificial chromosomes (YACs) in the study of globin gene switching by producing new shorter beta-YACs which will facilitate structural analysis and by developing methods to protect high molecular weight YAC DNA from the degradation. 2) To investigate the structure functional relationship of the locus control region and its role in globin switching. 3) To examine the molecular control of epsilon globin gene expression. 4) To investigate the control of the gamma-globin gene expression. 5) To investigate the relationship between the spatial gene order and the temporal order of developmental expression of globin genes, and 6) To develop in vivo binary assays for studying trans-control of switching. It is hoped that with a better understanding of this system and transacting elements involved in globin gene control during development and differentiation, new insights will emerge which will suggest strategies for the manipulation of fetal hemoglobin expression in the treatment of patients with sickle cell anemia or beta-thalassemia syndromes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK045365-06
Application #
2016545
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Badman, David G
Project Start
1992-09-30
Project End
2002-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
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