Abstract

We plan to develop methods for the prenatal diagnosis of sickle cell anemia and thalassemia, to study evolution of the sickle gene in human populations, and to investigate the molecular mechanism underlying abnormal globin production in thalassemia. In prenatal diagnosis, we will search for polymorphism in DNA sequence which can be used for linkage analysis of the sickle gene and the different types of beta thalassemia genes. We will devise methods to analyze directly the nucleotide change in the sickle mutation. We will also use molecular cloning to study the divergence between the nucleotide sequence of the S and C gene to determine their evolutionary lineage. In beta thalassemia, we plan to search for different types of nonsense mutations as the cause for beta thalassemia. We will first utilize the suppressor tRNA assay to detect nonsense mutation and determine the exact mutations by cloning the gene and sequence analysis. In alpha thalassemia, we will study the mechanism of production of the non-deletion type of alpha thalassemia by molecular cloning of the DNA, determination of their structures by sequences analysis, and assaying the function of these genes in in vitro systems.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM016666-13
Application #
3151021
Study Section
(EH)
Project Start
1976-08-01
Project End
1986-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
13
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Chang, Judy C; Ye, Lin; Kan, Yuet Wai (2006) Correction of the sickle cell mutation in embryonic stem cells. Proc Natl Acad Sci U S A 103:1036-40
Han, X; Kasahara, N; Kan, Y W (1995) Ligand-directed retroviral targeting of human breast cancer cells. Proc Natl Acad Sci U S A 92:9747-51
Kasahara, N; Dozy, A M; Kan, Y W (1994) Tissue-specific targeting of retroviral vectors through ligand-receptor interactions. Science 266:1373-6
Chehab, F F; Der Kaloustian, V; Khouri, F P et al. (1987) The molecular basis of beta-thalassemia in Lebanon: application to prenatal diagnosis. Blood 69:1141-5
Chan, V; Chan, T K; Ghosh, A et al. (1987) Application of DNA polymorphisms for prenatal diagnosis of beta thalassemia in Chinese. Am J Hematol 25:409-15
Chan, V; Chan, T K; Chebab, F F et al. (1987) Distribution of beta-thalassemia mutations in south China and their association with haplotypes. Am J Hum Genet 41:678-85
Conboy, J; Kan, Y W; Shohet, S B et al. (1986) Molecular cloning of protein 4.1, a major structural element of the human erythrocyte membrane skeleton. Proc Natl Acad Sci U S A 83:9512-6
Conboy, J; Mohandas, N; Tchernia, G et al. (1986) Molecular basis of hereditary elliptocytosis due to protein 4.1 deficiency. N Engl J Med 315:680-5
Ho, Y S; Norton, G P; Palese, P et al. (1986) Expression and function of suppressor tRNA genes in mammalian cells. Cold Spring Harb Symp Quant Biol 51 Pt 2:1033-40
Kan, Y W (1986) The William Allan Memorial Award address: Thalassemia: molecular mechanism and detection. Am J Hum Genet 38:4-12

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