title: Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in beta-thalassemia and sickle cell anemia patients.
abstract: We have studied 42 homozygous beta-thalassemia patients from Algeria and 34 sickle cell anemia patients from Senegal and Benin, determining the relationship between haplotypes, Hb F, and G gamma-globin/A gamma-globin ratios. Populations selected have a high frequency of haplotype homozygotes because of consanguinity (Algeria) and geographic homogeneity (West Africa). We find in beta-thalassemia patients, that haplotype IX in haplotypic homozygotes and heterozygotes, haplotype III in heterozygotes, and the Senegal haplotype in sickle cell anemia patients are all linked to high G gamma-globin expression. In addition, haplotypes IX and Senegal, but not haplotype III, have high Hb F levels. All of these haplotype have a common subhaplotype (+- ) in the gamma-globin gene region. In addition, haplotypes IX, III, and Senegalese sickle cell anemia patients exhibit hematological amelioration of their disease. Conversely, haplotypes I, V, and A in thalassemia patients, which also have a common subhaplotype (-----), and the Benin subhaplotype (--++-) in sickle cell anemia patients are all associated with low G gamma-globin and low Hb F levels. Low G gamma-globin expression in the adult is associated with two haplotypes that are not common between thalassemia and sickle cell anemia patients. We conclude that the determinant for high G gamma-globin expression is haplotype-linked to common and genetically dominant subhaplotypes in the two diseases. The total Hb F level, unlike the high G gamma-globin expression, however, is linked to haplotypes but not to subhaplotypes, thus dissociating the two genetic effects.
authors.forename: D
authors.initials: D
authors.lastname: Labie
authors.forename: J
authors.initials: J
authors.lastname: Pagnier
authors.forename: C
authors.initials: C
authors.lastname: Lapoumeroulie
authors.forename: F
authors.initials: F
authors.lastname: Rouabhi
authors.forename: O
authors.initials: O
authors.lastname: Dunda-Belkhodja
authors.forename: P
authors.initials: P
authors.lastname: Chardin
authors.forename: C
authors.initials: C
authors.lastname: Beldjord
authors.forename: H
authors.initials: H
authors.lastname: Wajcman
authors.forename: M E
authors.initials: ME
authors.lastname: Fabry
authors.forename: R L
authors.initials: RL
authors.lastname: Nagel
mesh_terms: D000755:Anemia, Sickle Cell / Q000235:genetics*; D002675:Child, Preschool; D005319:Fetal Hemoglobin / Q000032:analysis*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006801:Humans; D007223:Infant; D013789:Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin