Diverse genetic mechanisms operate to generate atypical beta(S) haplotypesin the population of Guadeloupe

In a survey of the chromosomal background associated with the sickle cell g ene in Guadeloupe, a French Caribbean island, we identified 37 unrelated pa tients with sickle cell disease (27 SS, nine SC, and one S-beta-thalassemia ) of 477 unrelated sickle cell patients where the beta(S) gene was linked t o 20 different atypical haplotypes. These atypical chromosomes account for about 5% of the overall beta(S) chromosomes in this population. To investig ate the origin of these atypical beta(S) haplotypes, we performed extensive typing of beta(S) and beta(A) chromosomes. Twenty-two different 5' subhapl otypes were identified among the beta(S) chromosomes. Fifteen of 20 differe nt atypical haplotypes are likely to be the product of recombination by a s ingle crossover around the "hot-spot" 5' to the beta-globin gene, or betwee n a major beta(S) haplotype and one of the beta(S) haplotypes present in th e population. The remaining cases require genetic mechanisms (gene conversi ons, additional substitutions in a given haplotype) other than crossovers t o generate these atypical haplotypes.