title: Developmental effect of the XmnI site on Ggamma-globin gene expression among newborn Hb F-Malta-I [Ggamma117(G19)His-->Arg, CAT-->CGT] heterozygotes and adult beta+ -Thalassemia homozygotes.
abstract: Hb F-Malta-I [Ggamma117(19)His-->Arg, CAT-->CGT] is a stable and benign variant of Hb F found in 1.8% of Maltese newborn. We studied 120 Hb F-Malta-I heterozygotes and four Hb F-Malta-I homozygotes. The mean proportion of Ggamma-F-Malta-I in Hb F was 0.26 +/- 0.03 for the Hb F-Malta-I heterozygotes and 0.58 +/- 0.06 for the Hb F-Malta-I homozygotes. The Hb F-Malta-I allele was shown to occur on a background of the common Mediterranean haplotype Va [+ + - - - - - + + -]. Furthermore, the common Mediterranean haplotypes Va, IIIb [- + + + - + + + + -], I [+ + - - - - - + + +] and II [- + - + + - + + + +] accounted for most (66.2%) of the wild-type alleles among the tested Hb F-Malta-I heterozygotes. Different genotypes at the 5' epsilon HincII, Ggamma and Agamma HindIII, and 3'psibeta HincII sites (but not at the 5' Ggamma XmnI site) were found to be linked to significant variations in the proportion of Ggamma-F-Malta-I and Ggamma-globins in the Hb F of newborn Hb F-Malta-I heterozygotes. Moreover, the 5' Ggamma XmnI site was found to be associated with variations in Hb F and Ggamma-globin levels in a population of adult Maltese beta-thalassemia (thal) homozygotes. This implies that a determinant linked to the XmnI site which effects Ggamma-globin gene expression is active in anemic adults but not in normal infants.
authors: Laboratory of Molecular Genetics, Department of Physiology and Biochemistry, University of Malta, Msida, Malta. svetlanapulis@hotmail.com
authors: Svetlana
authors: S
authors: Pulis
authors: Christian A
authors: CA
authors: Scerri
authors: Pierre Schembri
authors: PS
authors: Wismayer
authors: Ruth
authors: R
authors: Galdies
authors: Stephanie Bezzina
authors: SB
authors: Wettinger
authors: Alex E
authors: AE
authors: Felice
mesh_terms: D000328:Adult; D005312:Fetal Blood / Q000737:chemistry; D005319:Fetal Hemoglobin / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006239:Haplotypes; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007525:Isoelectric Focusing; D008319:Malta; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; C068751:hemoglobin F Malta I; D005914:Globins; D005319:Fetal Hemoglobin