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The breakpoints of alpha-thalassemia-1 were thoroughly characterized in two Japanese families. The crossover occurred between Alu repeats at about 1.28 kb 5' to the zeta2 gene and about 1.2 kb 3' to the theta1 gene, resulting in the deletion of a 30.656 kb-long segment. These breakpoints are consistent with those surmised for the "Filipino type (--FIL)" deletion by Southern blot analysis. Also the length of the 3' hypervariable region of the alpha-globin gene conformed to that of --FIL. The two Japanese families are related to the Taiwanese and Filipino families.

Characterization of beta-thalassemia mutations were attempted for 29 Japanese families clinically diagnosed as having beta-thalassemia. Following the identification of a mutation by cloning and sequencing, all families were screened for this particular mutation, using biotinylated allele-specific oligonucleotide probes. Seven different mutations were detected in 17 families: Six families had the frameshift mutation at codons 41/42, resulting from a 4 nucleotide deletion (TTCTTT----TT); four had the deletion at codons 127/128 (CAGGCT----CCT); and three had the TATA box mutation at nucleotide -31 (A----G). Four additional families had mutations at codon 24 (GGT----GGA), codon 26 (GAG----AAG), IVS-II-654 (C----T) and codon 110 (GTG----CCG), respectively. The newly discovered deletion mutation at codons 127/128, and mutations at nucleotide -31, and at codon 110 are peculiar to Japanese, and have not been found in any other ethnic group. The haplotypes of the beta-globin gene cluster were also determined. Some of the haplotypes and beta-thalassemia mutations are identical to those reported in the Chinese population. However, it is noteworthy that nearly half of the beta-thalassemia mutations were unique to Japanese.