title: Diverse genetic mechanisms operate to generate atypical betaS 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-beta-thalassemia) of 477 unrelated sickle cell patients where the beta3 gene was linked to 20 different atypical haplotypes. These atypical chromosomes account for about 5% of the overall betaS chromosomes in this population. To investigate the origin of these atypical betaS haplotypes, we performed extensive typing of betaS and betaA chromosomes. Twenty-two different 5' subhaplotypes were identified among the betaS 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 beta-globin gene, or between a major betaS haplotype and one of the betaS haplotypes present in the population. The remaining cases require genetic mechanisms (gene conversions, additional substitutions in a given haplotype) other than crossovers to generate these atypical haplotypes.
authors.affiliation: Unité de Recherche sur la Drépanocytose, INSERM U 516 Centre Hospitalier Universitaire de Pointe-à-Pitre Guadeloupe, French West Indies. marc.romana@guadeloupe.inserm.fr
authors.forename: M
authors.initials: M
authors.lastname: Romana
authors.forename: L
authors.initials: L
authors.lastname: Kéclard
authors.forename: A
authors.initials: A
authors.lastname: Froger
authors.forename: E
authors.initials: E
authors.lastname: Lavocat
authors.forename: C
authors.initials: C
authors.lastname: Saint-Martin
authors.forename: C
authors.initials: C
authors.lastname: Berchel
authors.forename: G
authors.initials: G
authors.lastname: Mérault
mesh_terms: D003625:Data Collection; D014644:Genetic Variation; D019430:Guadeloupe / Q000453:epidemiology; D006239:Haplotypes / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D015183:Restriction Mapping
chemical_list: D006451:Hemoglobin, Sickle