Structural analysis on the abnormal elongated hemoglobin "hemoglobin Geneva".

Hemoglobin variants in which a frameshift results in chain elongation are not common. Hemoglobin Geneva (HbGeneva) is an unstable hemologin with abnormal elongation. This hemoglobinopathy is known for its high instability. Concerning the pathogenesis of HbGeneva, the data indicate a change in codon 114 from CTG (Leu) to -GG that results in a frame shift and the presumed synthesis of an abnormal beta-chain that is 156 residues long with a completely different C-terminal amino acid sequence. This abnormality causes a frame shift, which results in elongation of the beta-chain amino acids. A bioinformatic analysis was performed to study the secondary and tertiary structures of those abnormal amino acid sequences. A computer-based study for protein structure modeling was performed. According to this study, the secondary structure analysis of the Hb Geneva showed many defects in helix and strand of the Hb Geneva compared with normal beta-globin chains. On the basis of this information, the main alteration in the Hb Geneva might be due to these aberrations. With regard to the tertiary structure, the deterioration of folds, accompanied by the aberration in secondary structure of globin in Hb Geneva can be identified.