The Indian rubber estate workers in Negri Sembilan, Malaysia, who originated from Orissa in India were found to have a high frequency of Hb S (Joishy SK, Hassan K: Clin Res 28:280, 1980). Unlike the usually severe clinical picture of
sickle cell anemia seen in African and American blacks, the clinical picture of the disease in this population was mild and many have reached old age. We studied the leukocyte
DNA of 12 patients with
sickle cell anemia, ranging in age from 4 to 61 years and 30
sickle cell trait carriers, ranging in age from 7 to 63 years, for the presence of
alpha-globin gene deletions by gene mapping according to Southern (Southern EM: J Mol Biol 98:503, 1975), using alpha- and
zeta-globin gene probes obtained by nick translation of the alpha- and
zeta-globin genes cloned into plasmid. All 12
sickle cell anemia patients were found to have alpha-thalassemia2 (alpha-thal2), either in the homozygous or heterozygous condition. Of the Hb S trait carriers, six did not have alpha-thal2 or alpha-thal1 and 24 had alpha-thal2 (15 heterozygous, 9 homozygous). Seven of these Hb S trait carriers with alpha-thal2 had an additional gene abnormality. Five of them had a fast-moving
Eco RI fragment 5.6 kb long that hybridized with zeta-specific probe but not with alpha-specific probe. An unusual
DNA pattern of a different type was further found in the other two. Bgl II restriction analysis showed that the alpha-thal2 was mostly of the rightward deletion alpha-thal1 genotype. None of the
sickle cell anemia patients and Hb S trait carriers had deletion type alpha-thal1. The
sickle cell anemia patients had very high levels of Hb F and low levels of
Hb A2. The Hb S trait carriers with alpha-thal2 had relatively low levels of Hb S.