title: Annotated definition of BCL11A and HMIP-2 haplotypes through the analysis of sicilian β-thalassemia patients with high levels of fetal hemoglobin.
abstract: Fetal hemoglobin (Hb F) is the principal ameliorating factor of β-thalassemia (β-thal) and sickle cell disease. Persistent production in adult life is a quantitative trait regulated by loci inside or outside the β-globin gene cluster. From genome-wide association studies, principal quantitative trait loci (QTL) (accounting for 50.0% of Hb F variability in different populations) have been identified in the BCL11A gene, HBS1L-MYB intergenic polymorphism and the β-globin gene cluster itself. In this study, we analyzed quantitative trait haplotypes in two Sicilian families with extremely mild β-thal and unusually high Hb F expression, in order to examine possible genetic background variations in a similar β-thalassemic phenotype. This study redefines the linkage disequilibrium blocks at these loci, but also shows slight differences between probands in haplotype combinations which could reflect different mechanisms of high Hb F production in patients with β-thal. We proposed a haplotype-based approach as a useful tool for the understanding of β-thal phenotype variation in patients with similar β-thalassemic backgrounds in an attempt to answer the recurring question of why patients with the same β-thalassemic genotype show different phenotypes.
authors.affiliation: Unità Operativa Complessa Prenatal Diagnosis and Medical Genetics, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, Catania, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Buccheri
authors.forename: Sonia
authors.initials: S
authors.lastname: Spina
authors.forename: Concetta
authors.initials: C
authors.lastname: Ruberto
authors.forename: Turi
authors.initials: T
authors.lastname: Lombardo
authors.forename: Dominique
authors.initials: D
authors.lastname: Labie
authors.forename: And Angela
authors.initials: AA
authors.lastname: Ragusa
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics; D005192:Family Health; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010445:Peptide Elongation Factors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D012097:Repressor Proteins; D012802:Sicily; D055542:alpha-Globins / Q000235:genetics; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000235:genetics* / Q000378:metabolism
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D021901:DNA, Intergenic; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D055542:alpha-Globins; D055544:beta-Globins; D005319:Fetal Hemoglobin; D019204:GTP-Binding Proteins; C000628258:HBS1L protein, human