3′ haplotypes of the β-globin gene in βs-chromosomes of Mexican individuals

The β-globin gene cluster has shown high polymorphic diversity organized in 5′ and 3′ haplotypes (Hps). βS-Chromosomes are in linkage disequilibrium with the 5′ Hps Bantu, Benin, Senegal, Cameroon, and Arab–Indian. In Mexican mestizos with African west coast origins, we observed the following 5′ Hps in βS-chromosomes: Bantu, 78.8%; Benin, 18.2%; and atypical Hp 9, 3.0%. With the purpose of establishing the 3′ Hps, we analyzed 35 polymorphic sites—6 by RFLP analysis and 29 by DNA sequencing—in 33 unrelated βS-chromosomes. The polymorphic sites were structured according to Harding et al. [R.M. Harding, S.M. Fullerton, R.C. Griffiths, J.B. Clegg, Archaic African and Asian lineages in the genetic ancestry of modern humans, Am. J. Hum. Genet. 60 (1997) 772–789] and Lapouméroulie et al. [C. Lapouméroulie, O. Dunda, R. Ducrocq, G. Trabuchet, M. Mony-Lobé, J.M. Bodo, P. Carnevale, D. Labie, J. Elion, R. Krishnamoorthy, A novel sickle cell mutation of yet another origin in Africa: the Cameroon type, Hum. Genet. 89 (1992) 333–337]. All Bantu βS-chromosomes showed the 12A1 3′ Hp with (AT)6T9 repeats (84.9%), a novel 3′ Hp. The Benin Hp was 2B2, with (AT)8T4 (12.1%), and the atypical Hp 9 4B1, (AT)8T5 (3.0%). Because of the high linkage disequilibrium observed for the Bantu and 12A1 Hps, we expect that, if there is a single origin of the Bantu βS mutation, all must show the 12A1 polymorphic DNA sequence in the 3′ Hp. A correlation between the 5′ and 3′ Hps could be observed with the other βS mutations. The atypical Hp 9 was also atypical at the 3′ Hp, with the same repeats as observed with the Cameroon βS mutation; however, it differed in one position from the typical Lapouméroulie Cameroon Hp, indicating that these βS-chromosomes arose by different genetic mechanisms or by a novel βS mutation. We stress the importance of the study of DNA polymorphisms at 3′ Hp to allow understanding of the genetic diversity of βS-chromosomes, as well as their implications in βS gene expression and the possible effects on the clinical phenotype.