Gene mapping of malaysian α thalassemias with α and ζ globin gene probes

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Abstract
Restriction enzyme analysis of the α and ζ globin genes was carried out in four cases of Hb Bart's hydrops fetalis, in three patients with Hb H disease without Hb CoSp, in three patients with Hb H disease with Hb CoSp, in 47 individuals with α thalassemia trait, and in 47 normal individuals. All four cases of Hb Bart's hydrops fetalis resulted from deletions of α1 and α2 globin genes which did not extend to the ψζ1 and ζ2 globin genes. The same type of deletion was observed in α thal1 carriers, but two newborns (one Malay and one of Chinese extraction) had a nondeletion type of α thal1 which was confirmed by quantitative αglobin gene analysis. In addition, two other newborns diagnosed as α thal1 trait carriers (one Malay, one Chinese) were shown to have a deletion of both α globin genes by quantitative α globin gene analysis, but further testing with ζ globin gene probe failed to reveal an abnormal fragment length characteristic of an α globin gene deletion. We believe that this last condition is due to a large deletion which includes all α globin genes and all ζ globin genes on the same chromosome. On another front, Bgl II restriction analysis of all four Hb Bart's hydrops fetalis cases and the α thal1 trait carriers showed a 10.5‐kb Bgl II restriction fragment, in the hydrops fetalis as a single band, while in the carriers this 10.5‐kb fragment was accompanied by the usual normal 12.5‐kb and 11.3‐kb fragments. We report that this 10.5‐kb fragment, previously thought to be specific for the Southeast Asian α thal1 gene deletion, is also common in normal individuals. Nevertheless, digestion with other enzymes can clearly differentiate the α thal1 and normal genotypes. We distinguish the findings in the α thalassemias from the extensive DNA polymorphism in the region of the α and ζ globin genes.