Abstract

Human hemoglobin disorders cause much morbidity and mortality throughout the world. New methods of studying genes, particularly restriction endonuclease analysis by gel electrophoresis and blotting, and sequencing of DNA in molecular clones, have allowed much recent progress in the study of normal human globin genes and their alterations in these disorders. This proposal describes analysis of specific DNA defects in beta thalassemia, study of the switchover from fetal to adult hemoglobin synthesis using nondeletion types of hereditary persistence of fetal hemoglobin, and comparison of mild and severe thalassemia, and investigation of alpha-globin gene expression in alpha-gene variants. These studies will relate results by their newer technics to those obtained by hematological, genetic, and biochemical methods. The long-term objective of this project is to provide information which will be of use in diagnosis and therapy of patients with hemoglobin disorders.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK016691-14
Application #
3225627
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1977-05-01
Project End
1987-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
14
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Graves, D J (1999) Powerful tools for genetic analysis come of age. Trends Biotechnol 17:127-34
Adachi, K; Yamaguchi, T; Pang, J et al. (1998) Effects of increased anionic charge in the beta-globin chain on assembly of hemoglobin in vitro. Blood 91:1438-45
Cui, Z; Reilly, M P; Surrey, S et al. (1998) -245 bp of 5'-flanking region from the human platelet factor 4 gene is sufficient to drive megakaryocyte-specific expression in vivo. Blood 91:2326-33
Graves, D J; Su, H J; McKenzie, S E et al. (1998) System for preparing microhybridization arrays on glass slides. Anal Chem 70:5085-92
Yamaguchi, T; Pang, J; Reddy, K S et al. (1998) Role of beta112 Cys (G14) in homo- (beta4) and hetero- (alpha2 beta2) tetramer hemoglobin formation. J Biol Chem 273:14179-85
McKenzie, S E; Mansfield, E; Rappaport, E et al. (1998) Parallel molecular genetic analysis. Eur J Hum Genet 6:417-29
Norris, C F; Pricop, L; Millard, S S et al. (1998) A naturally occurring mutation in Fc gamma RIIA: a Q to K127 change confers unique IgG binding properties to the R131 allelic form of the receptor. Blood 91:656-62
Reddy, L R; Reddy, K S; Surrey, S et al. (1997) Role of beta87 Thr in the beta6 Val acceptor site during deoxy Hb S polymerization. Biochemistry 36:15992-8
Adachi, K; Konitzer, P; Pang, J et al. (1997) Amino acids responsible for decreased 2,3-biphosphoglycerate binding to fetal hemoglobin. Blood 90:2916-20
Mansfield, E S; Vainer, M; Harris, D W et al. (1997) Rapid sizing of polymorphic microsatellite markers by capillary array electrophoresis. J Chromatogr A 781:295-305

Showing the most recent 10 out of 36 publications