Beta-Globin Gene Cluster Haplotypes as Evidence of African Gene Flow to the Northeastern Coast of Venezuela MERLYN VI Â VENES DE LUGO, ALVARO RODRI Â GUEZ-LARRALDE, AND DINORAH CASTRO DE GUERRA* Instituto Venezolano de Investigaciones Cientõ Âficas (IVIC), Centro de Medicina Experimental, Laboratorio de Gene Âtica Humana, Caracas 1020 A, Venezuela ABSTRACT In order to study the origin of mutation HBB*S in Sucre and Anzoa Âtegui states and the genetic affinities of these Venezuelan populations with other human groups, the b-globin gene cluster haplotypes were determined for 28 sickle cell and/or S-beta thalassemia patients and for 37 individuals with normal hematological parameters. Bantu, Benin, Senegal, and atypical haplotypes were identified in 50%,36%,2%, and 12% of the HBB*S chromosomes, respectively. Similar results have been published for Venezuelan patients from the central states, but a different trend is shown in a publication based on a group of patients from different regions of the country. For HBB*A, haplotype 2 (), characteristic of non-African groups, was the most common (39%), followed by haplotype 3 () of African origin, and haplotype 6(), also typical of non-Africans. The results reveal a high level of admixture of the Sucre±Anzoa Âtegui population. The importance of specific conditions which have acted differently in the Venezuelan populations, such as founder effect, genetic drift, isolation, and endogamy are discussed. Genetic distances between the Sucre±Anzoa Âtegui sample and several other human populations calculated on the basis of the HBB*S and HBB*A haplo- types revealed similar results, the closest genetic relationships being observed in relation to Bantu-speaking groups. These results confirm the utility of the b-globin haplotypes for popula- tion studies and contribute to knowledge of the Venezuelan gene pool. Am. J. Hum. Biol. 15:29±37, 2003. # 2002 Wiley-Liss, Inc. The HBS mutation (b6 Glu!!Val) has been associated with five main haplotypes usually defined by six polymorphic restriction endo- nuclease sites in and around the b-like globin gene: Benin (BEN: ), Central African Republic or Bantu (CAR or BAN: ), Senegal (SEN: ), Cameroon (CAM: ) and Arab- Indian (ARB: ), which are probably related to the clinical heterogeneity ofsicklecellanemia(Nageletal.,1987,1991; Elion et al., 1992). The presence of these haplotypes can also suggest the place of origin of mutation HBB*S in the population under study (Gonc Ëalves et al., 1994; Steinberg et al., 1997; Pante de Sousa, 1999). On the other hand, analysis of haplotypes associatedwiththenormalallele,HBB*A,are useful in studies of genetic diversity and interpopulation relationships. Wainscoat et al. (1986) were the first to carry on this type of investigation using RFLPs in the b-globin gene cluster. Subsequently, Long et al. (1990) and Chen et al. (1990) revealed that Africans can be distinguished from non-Africans through distributions of five haplotypes: 2 (),3(), 4(),5(),and6( ). Haplotypes 3 and 4 have been considered common genetic markers of African popula- tions, while haplotype 2 is characteristic of non-Africans. Allele HBB*S was introduced into Venezuela by migratory waves from Africa during the slave trade. HBB*S is more frequent among African descendants, who inhabit an extensive coastal region from the East to the West of the country (Acosta Saignes, 1969; Castro de Guerra, 1992). Molecular studies of the b-globin gene clusters in Venezuelans are scarce, but the predominance of the Bantu haplotype (47%) has been reported in patients with sickle cell anemia from Carabobo and Cojedes states and from the central-western region, ß 2002 Wiley-Liss, Inc. Contract grant sponsors: IVIC and CONICIT (to MVL). *Correspondence to: Dinorah Castro de Guerra, Laboratorio de GeneÂtica Humana, IVIC, Apdo. 21827, Caracas 1020-A, Venezuela. E-mail: dcastro@ivic.ve Received 22 October 2001; Revision received 25 June 2002; Accepted 5 July 2002 Published online in Wiley InterScience (www.interscience. wiley.com). DOI: 10.1002/ajhb.10120 AMERICAN JOURNAL OF HUMAN BIOLOGY 15:29±37 (2003)