The interaction of anti 3.7 type quadruplicated alpha-globin genes and heterozygous beta-thalassemia

Human alpha-globin gene mapping was carried out using a variety of restriction endonucleases (Bgl II, Bam HI, Hind III, Eco RI, Hpa I, Pvu II and Rsa I) on members of a family from El Salvador and a female from Hawaii, of Chinese descent, whose hematological and clinical parameters were those of beta-thalassemia intermedia. Southern blot DNA analysis showed that the beta-thalassemia intermedia patients from the above two families had the same anti 3.7 type quadruplicated alpha-genes on the one chromosome, and that they had the alpha genotype alpha 2, alpha 1 alpha 2, alpha 1 alpha 2, alpha 1/alpha 2, alpha 1. The alpha/beta globin synthesis ratios of the three affected Salvadoran patients were around 2.5, and the affected Hawaiian patient was 2.9. These ratios strongly suggest that the additional alpha-genes in the anti 3.7 type rearrangement are biologically active, thus accounting for the severity of the heterozygous beta-thalassemia observed among these patients.