3' haplotypes of the beta-globin gene in beta(S)-chromosomes of Mexican individuals.
The beta-globin gene cluster has shown high polymorphic diversity organized in 5' and 3' haplotypes (Hps). beta(S)-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 beta(S)-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 beta(S)-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 Lapoumeroulie et al. [C. Lapoumeroulie, O. Dunda, R. Ducrocq, G. Trabuchet, M. Mony-Lobe, 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 beta(S)-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 beta(S) 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 beta(S) mutations. The atypical Hp 9 was also atypical at the 3' Hp, with the same repeats as observed with the Cameroon beta(S) mutation; however, it differed in one position from the typical Lapoumeroulie Cameroon Hp, indicating that these beta(S)-chromosomes arose by different genetic mechanisms or by a novel beta(S) mutation. We stress the importance of the study of DNA polymorphisms at 3' Hp to allow understanding of the genetic diversity of beta(S)-chromosomes, as well as their implications in beta(S) gene expression and the possible effects on the clinical phenotype.
Magaña
María Teresa
MT
División de Genética, Centro de Investigación Biomédica de Occidente, CMNO, IMSS, Sierra Mojada No. 800, Guadalajara, Jalisco, Mexico.
Perea
F Javier
FJ
Ongay
Zoila
Z
Ibarra
Bertha
B
D002877:Chromosomes, Human / Q000235:genetics*; D005914:Globins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008800:Mexico / Q000208:ethnology; D011110:Polymorphism, Genetic / Q000235:genetics
D005914:Globins