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Dissection of the association status of two polymorphisms in the β‐globin gene cluster with variations in F‐cell number in non‐anemic individuals
Author(s) -
Merghoub Taha,
Perichon Bruno,
MaierRedelsperger Micheline,
Dibenedetto Salvatore Pietro,
Samperi Piera,
Ducrocq Rolande,
Feingold Nicole,
Elion Jacques,
Schiliro Gino,
Labie Dominique,
Krishnamoorthy Rajagopal
Publication year - 1997
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/(sici)1096-8652(199712)56:4<239::aid-ajh7>3.0.co;2-y
Subject(s) - biology , genetics , locus (genetics) , fetal hemoglobin , locus control region , haplotype , heterozygote advantage , globin , sickle cell anemia , microbiology and biotechnology , gene , linkage disequilibrium , gene cluster , hemoglobin , hemoglobinopathy , gene expression , allele , cell , promoter , hemolytic anemia , immunology , fetus , pregnancy , biochemistry
Expression of fetal hemoglobin (Hb F) is under polygenic control involving determinants both linked and unlinked to the β‐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 Gγ‐gene (detected as an Xmn I polymorphism) correlate with the high level of Hb F expression in patients with sickle‐cell anemia and β‐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 β S ‐chromosome of all these individuals was of the Benin haplotype and they differed only by their β A chromosomes. We demonstrate that F‐cell expression is more strongly associated with LCR‐HS2 polymorphism than with Xmn I polymorphism. The observed association between Xmn I polymorphism and Hb F expression is very likely to be due to linkage disequilibrium with LCR‐HS2 sequences. Am. J. Hematol. 56:239–243, 1997. © 1997 Wiley‐Liss, Inc.