The origin of the sickle mutation in Greece; evidence from beta S globin gene cluster polymorphisms.

Study of the Hpa I polymorphism 3' to the beta-globin gene in the Greek population revealed absence of the site in 238 beta S chromosomes, in contrast to a much larger sample of chromosomes carrying the beta A gene, where this site was consistently positive. Subsequent haplotype analysis of the beta-globin gene cluster in 82 beta S chromosomes demonstrated that 79 (96%) belonged to haplotype #19, while the three exceptions (all Hpa I negative) could be explained by a delta-beta recombination event. Haplotype #19 was never encountered in a parallel study of the 83 beta A chromosomes. Comparison of the above results with similar surveys in other parts of the world and consideration of various historical events suggest that the beta S mutation was introduced into Greece over the last few centuries by the Saracen raids and/or by settlements of North African slaves brought in by the Arabs, Franks, Venetians, or Ottoman Turks, who have occupied the country over the last millennium.