Diverse Genetic Mechanisms Operate to Generate Atypical β^s Haplotypes in the Population of Guadeloupe

Abstract

In a survey of the chromosomal background associated with the sickle cell gene in Guadeloupe, a French Caribbean island, we identified 37 unrelated patients with sickle cell disease (27 SS, nine SC, and one S-β-thalassemia) of 477 unrelated sickle cell patients where the β^s gene was linked to 20 different atypical haplotypes. These atypical chromosomes account for about 5% of the overall β^s chromosomes in this population. To investigate the origin of these atypical β^s haplotypes, we performed extensive typing of β^s and β^Achromosomes. Twenty-two different 5' subhaplotypes were identified among the β^s chromosomes. Fifteen of 20 different atypical haplotypes are likely to be the product of recombination by a single crossover around the <<hot-spot>> 5' to the β-globin gene, or between a major β^s haplotype and one of the β^s haplotypes present in the population. The remaining casm require genetic mechanisms (gene conversions, additional substitutions in a given haplotype) other than crossovers to generate these atypical haplotypes.