Point mutations of the !-globin gene

Over 300 point mutations in the !-globin gene
and over 100 in one of the "-globin genes have
been documented. Two clinically important
mutations affect codon 6: the sickle cell mutation,
6 Glu ! Val (sickle cell hemoglobin, HbS,
resulting in the incorporation of valine instead
of glutamic acid) and 6 Glu ! Lys (hemoglobin
C, HbC, incorporating lysine instead of glutamic
acid in codon 6). Compound heterozygoteswith
the HbS mutation on one chromosome and the
HbC on the other (HbSC) are not rare. The
marked methemoglobin formation in Hb Zürich
and Hb Saskatoon results fromsubstitutions for
histidine (His) in codon 63, which alter the oxygen-
binding region of the hemoglobin
molecule.