[Genetic aspects of sickle cell anemia]

The genetics of sickle cell anemia may be considered as a model. Its mendelian transmission was hypothesized even before the molecular era. Once the mutation identified, it could be studied at the protein and DNA level; a consistent pathophysiological mechanism was proposed; the various genetic forms of the disease could be identified; the way by which a balanced polymorphism with Plasmodium falciparum malaria is obtained was analyzed. More recently, investigations were run in order to understand how modulating, or epistatic factors could modify the pathophysiological mechanism and contribute to the high clinical diversity of the disease. Several factors have been identified, among which a concomitant alpha-thalassemia, an overproduction of fetal hemoglobin, due either to an activation of the gamma genes or to an increase of the F-cell number, and finally a quantitative control of the beta s chains themselves. Such a high number of genetic active factors questions the concept itself of a monogenic disease.