ANNOTATED DEFINITION OF BCL11A AND HMIP-2 HAPLOTYPES THROUGH THE ANALYSIS OF SICILIAN beta-THALASSEMIA PATIENTS WITH HIGH LEVELS OF FETAL HEMOGLOBIN

作者：Buccheri Maria A; Spina Sonia; Ruberto Concetta; Lombardo Turi; Labie Dominique; Ragusa Angela^*

来源：Hemoglobin, 2013, 37(5): 423-434.

DOI：10.3109/03630269.2013.800823

• Fetal hemoglobin (Hb F)
• BCL11A gene
• HBS1L-MYB intergenic polymorphism
• Haplotype
• Thalassemia

Fetal hemoglobin (Hb F) is the principal ameliorating factor of beta-thalassemia (beta-thal) and sickle cell disease. Persistent production in adult life is a quantitative trait regulated by loci inside or outside the beta-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 beta-globin gene cluster itself.
In this study, we analyzed quantitative trait haplotypes in two Sicilian families with extremely mild beta-thal and unusually high Hb F expression, in order to examine possible genetic background variations in a similar beta-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 beta-thal. We proposed a haplotype-based approach as a useful tool for the understanding of beta-thal phenotype variation in patients with similar beta-thalassemic backgrounds in an attempt to answer the recurring question of why patients with the same beta-thalassemic genotype show different phenotypes.

• 出版日期2013