Hb F Malta 1 : a biomarker for the developmental control of globin gene switching

Abstract

Introduction: Commonly occurring foetal haemoglobin variants (Hb F Malta 1 and Hb F Sardinia) were used as biomarkers in order to search for quantitative trait loci which are associated with the expression of foetal haemoglobin in the perinatal period. Methods: A total of 282 Hb F Malta 1 newborns were enrolled in the study. Reverse phase HPLC was used for globin chain quantification and several genotyping techniques were used to characterise known quantitative trait loci. Two Hb F Malta 1 homozygotes were sequenced with NGS to find regions which are coinherited with Hb F Malta 1. Results: BCL11A rs4671393 polymorphism was found to be associated with increased foetal haemoglobin. XmnI polymorphism was associated with increased γ-globin expression whilst Hb F Sardinia compound heterozygotes were found to have increased Hb F Malta 1. Several upstream and downstream olfactory genes are coinherited with Hb F Malta 1. These regions are thought to contain foetal haemoglobin enhancer regions. Conclusion: The significance of XmnI polymorphism suggests the presence of stress erythropoiesis in the newborn. A BCL11A variant delays the foetal to adult haemoglobin switching. Further research with NGS might reveal long range regulatory regions. Disclosures: This study was funded by the Endeavour Scholarship Scheme