The hematologic characteristics of sickle cell anemia bearing the Bantu haplotype: the relationship between G gamma and HbF level

Abstract

Previous work has demonstrated that the HbS gene has appeared and expanded three times in Africa in three separate geographic locations and that these three distinct mutational events can be identified by linked DNA polymorphic sites (haplotypes) surrounding the abnormal gene. We have reported that the Senegalese and Beninian haplotypes differ in G gamma expression, mean percentage of HbF, and percentage of dense cells. We now report on the third haplotype, the Bantu, and find that it has intermediate features, namely, the high mean percentage of HbF and low percentage of dense cells associated with the Senegalese haplotype, but with a low percentage of G gamma expression similar to the Beninian haplotype. The distribution of percent HbF is quite different from Senegal haplotype-bearing sickle cell anemia patients since it covers a much wider range. The low G gamma expression is also different from the Beninians since it contains a significant and unique cluster of individuals with lower than 38% G gamma. Interestingly, among the Bantu there is a strong correlation between HbF levels and G gamma expression, which is not seen with the other haplotypes. These findings open the possibility that among the Bantu haplotype-bearing individuals two chromosomal types exist that define different levels of G gamma and HbF expression. Further structural exploration of these two potential subhaplotypes is needed.

Acute chest syndrome is associated with single nucleotide polymorphism‐defined beta globin cluster haplotype in children with sickle cell anaemia

“…HbF level is partly controlled by genetic variation at the HBB cluster, although the exact responsible functional cis elements remain largely unknown (Dover et al, 1981;Nagel et al, 1985Nagel et al, , 1987Steinberg, 2005;Lettre et al, 2008;Galarneau et al, 2010). We found a clear connection between HbF level and SNP-defined b S -haplotypes in children with SCA.…”

Predicting clinical severity in sickle cell anaemia

“…The association of b-globin-like gene cluster haplotype with the severity of sickle cell anaemia must be cautiously interpreted and the prognostic value of knowing the haplotype in an individual is very limited. Studies of several different ethnic groups of patients with sickle cell anaemia with distinct haematological characteristics suggested that the b-globin gene cluster haplotype may be useful as one predictor of disease severity (Labie et al, 1985;Hattori et al, 1986;Kulozik et al, 1986Kulozik et al, , 1987Nagel et al, 1987;Ragusa et al, 1988;Sharon et al, 1988;Srinivas et al, 1988;Labie et al, 1989;Schroeder et al, 1989;Month et al, 1990;Ballas et al, 1991;Dimovski et al, 1991;Powars, 1991a,b;Nagel & Fleming, 1992;Zago et al, 1992;Ö ner et al, 1992). In the first studies of Africans and Indian patients, most patients were homozygous for a haplotype and genetically homogeneous compared with their descendants in developed countries studied subsequently.…”

Sickle cell anemia in Guadeloupean children: pattern and prevalence of acute clinical events

“…Comparison with other series suggests that the natural history of SCA in Guadeloupe is more similar to that in Jamaica with regard to those reported in Europe and the United States, suggesting a potential impact of environmental factors on the clinical course of the disease. haplotype (8)(9)(10)(11). Both affect the primary event of the SCA pathophysiological process, namely the intracellular polymerization of deoxyhemoglobin S which leads the red blood cell to sickle.…”