QUANTIFICATION OF (G)GAMMA-GLOBINS AND (A)GAMMA-GLOBINS BY ELECTROSPRAY-IONIZATION MASS-SPECTROMETRY

Elucidation of the molecular basis for persistent fetal haemoglobin (H b F) production in adult life has important implications for the patho physiology and treatment of human beta haemoglobinopathies. Electrospr ay ionisation mass spectrometry (ESMS) was applied to analyse the patt ern of gamma-globin expression in patients with hereditary persistence of fetal haemoglobin (HPFH) and sickle cell anaemia (SCA). (G)gamma a nd (A)gamma-globin chains were identified by their measured molecular masses and distinguished by mass difference (14 Dal following deconvol ution of ESMS spectra using maximum entropy based software. Prediction of HPFH type by ESMS was confirmed by molecular analysis. Direct dete rmination of (G)gamma:(A)gamma globin chain ratio from whole blood by the novel application of ESMS provides a rapid and sensitive approach to characterisation of gamma-globins and facilitates con elation of ga mma-globin level and polymorphism of cis-active elements at the beta-g lobin locus.