Diverse Genetic Mechanisms Operate to Generate Atypical β^sHaplotypes 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.

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

“…The sickle cell genotype was confirmed by amplification of the first exon of the β ‐globin gene and by allele‐specific‐oligonucleotide hybridization (15). α ‐Globin gene mapping and β S haplotypes characterization were performed as previously described (16, 17).…”

β‐Globin gene cluster haplotypes and α‐thalassemia in sickle cell disease patients from Trinidad

“…We also reported the a-thalassemia frequency in the pediatric patients and b-thalassemia alleles were identified. (Romana et al, 2000;Sutton et al, 1989). The following polymorphic restriction sites in the b-globin-like gene cluster were studied: HincII (5 0 to e), XmnI (5 0 to G g), Hind-III (IVS-II on G g and A g), HincII (within and 3 0 to b), and HinfI (5 0 and 3 0 to b).…”

Newborn Screening for Sickle Cell Disease in the Caribbean: An Update of the Present Situation and of the Disease Prevalence

“…In Saint Lucia, however, hemoglobin cellulose acetate and citrate agar electrophoresis are used locally for cord blood samples. In Guadeloupe, DNA analysis is also secondarily performed as a confirmatory diagnosis of a new sample (peripheral blood on EDTA as anticoagulant) in the following cases: FS phenotype when the two parents cannot be tested in order to distinguish SS, S/beta-thalassemia, or S/HPFH; and the FSX or FCX phenotype in order to formally identify the abnormal hemoglobin (HbX), as well as for ambiguous primary screening results [11,12].…”