Molecular Comparisons

As soon as an abnormal globin was found to cause sickle cell disease, scientists began looking for other variations. Samples were readily available from donors or from blood samples collected for medical tests. Within a few years, many alterations were identified; some changed the alpha globin amino acid sequence and others altered the beta chain. Most of the new alleles were named for the location in which they were found. Examples of local interest include Hb-Coushatta and Hb-Galveston, HbCowtown and Hb-Alamo among others. In nearly every case, when the amino acid sequences were determined, each variant represented a single missense mutation. Since most of the variants were initially detected by differences in electrophoretic mobility, the new forms generally resulted from changes involving arg, lys and his which have a positive charge under physiological conditions, or glu and asp which are negatively charged. For example the change in Hb-Coushatta is glu->ala as is the HbGalveston mutation, but the former occurs at position 22 of the beta chain while the latter is at amino acid 43.