title: Dissection of the association status of two polymorphisms in the beta-globin gene cluster with variations in F-cell number in non-anemic individuals.
abstract: Expression of fetal hemoglobin (Hb F) is under polygenic control involving determinants both linked and unlinked to the beta-globin gene cluster on chromosome 11. Variations in the DNase I-hypersensitive site 2 of the locus control region (LCR-HS2) and a C --> T change at position -158 from the Ggamma-gene (detected as an XmnI polymorphism) correlate with the high level of Hb F expression in patients with sickle-cell anemia and beta-thalassemia. Interpretation of data under these conditions of anemic stress is difficult because the preferential survival of Hb F-containing erythrocytes (F-cells) may not reflect the true status of Hb F expression. We investigated the relationship between these markers and Hb F expression in terms of F-cell levels in 48 unrelated non-anemic AS heterozygotes from Sicily. The betaS-chromosome of all these individuals was of the Benin haplotype and they differed only by their betaA chromosomes. We demonstrate that F-cell expression is more strongly associated with LCR-HS2 polymorphism than with XmnI polymorphism. The observed association between XmnI polymorphism and Hb F expression is very likely to be due to linkage disequilibrium with LCR-HS2 sequences.
authors.affiliation: INSERM U 458, Hôpital Robert Debré, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Merghoub
authors.forename: B
authors.initials: B
authors.lastname: Perichon
authors.forename: M
authors.initials: M
authors.lastname: Maier-Redelsperger
authors.forename: S P
authors.initials: SP
authors.lastname: Dibenedetto
authors.forename: P
authors.initials: P
authors.lastname: Samperi
authors.forename: R
authors.initials: R
authors.lastname: Ducrocq
authors.forename: N
authors.initials: N
authors.lastname: Feingold
authors.forename: J
authors.initials: J
authors.lastname: Elion
authors.forename: G
authors.initials: G
authors.lastname: Schiliro
authors.forename: D
authors.initials: D
authors.lastname: Labie
authors.forename: R
authors.initials: R
authors.lastname: Krishnamoorthy
mesh_terms: D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000032:analysis; D004906:Erythrocyte Count; D005260:Female; D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D005819:Genetic Markers; D005914:Globins / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics
chemical_list: D005819:Genetic Markers; D005914:Globins; D004247:DNA; D005319:Fetal Hemoglobin; C101716:DNA modification methylase XmnI; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)