To investigate whether recurrent mutation has contributed to the high frequency of the β(E)-globin gene in Southeast Asia, we used the haplotypes at three polymorphic restriction sites within and to the 3' side of the β-globin gene to predict the framework of 23 β(E)-globin genes. These haplotypes suggested that β(E)-globin genes are present in two different β-globin gene frameworks. DNA sequence determination of one gene representing each framework demonstrated that the same mutation (GAG → AAG at codon 26) was present in both frameworks. Moreover, the frameworks differed at three nucleotide positions known to be polymorphic in Mediterraneans. These polymorphic sites are located 70 nucleotides to the 5' side of the β(E) mutation and 382 and 1032 nucleotides to the 3' side of it. The existence of the β(E) mutation in these two β-globin gene frameworks can be explained by recurrent mutation giving rise to β(E)-globin, a double crossing-over event, or two single crossing-over events. Mathematical analysis suggests that the first alternative, recurrent mutation of G → A at the first nucleotide of codon 26, is most likely.
|Original language||English (US)|
|Number of pages||4|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Issue number||21 I|
|State||Published - 1982|
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