Thalassemia may be caused by different molecular defects in different areas of the world. We want to study cases of thalassemia by gene mapping using different restriction enzymes, by cloning and DNA sequencing in order to elucidate their molecular basis and contribute to our knowledge of the scope of variation in the molecular defect causing thalassemia. It may provide further important information on the genetics of hemoglobin synthesis. For this purpose we want to study cases of thalassemia from Malaysia and Indonesia where thalassemia is prevalent, where there are different ethnic groups so far not well explored and where we have access to study material through a long standing research collaboration. We want to determine polymorphisms in different racial groups at the gene level by studying restriction endonuclease sites around the globin gene region by restriction enzyme digestion and gene mapping. Studies have shown that human individuals may differ from one another by the length of different restriction DNA fragments due to variation in the DNA nucleotide sequences around the Alpha and Alpha-like globin genes as well as around the Beta and Beta-like globin genes. This provides a means of characterizing individuals and populations at the gene level. We want to characterize the different groups found in Malaysia and Indonesia by restriction mapping of genomic DNA, using different enzymes and different globin gene probes. We want to examine patients with thalassemia and their relatives to detect certain polymorphisms possibly linked to thalassemia, and determine their haplotypes according to Orkin et al. (l982, l983). This will be combined with direct study of the structure of the globin gene.