2 DIFFERENT MUTATIONS IN CODON-68 ARE OBSERVED IN HB G-PHILADELPHIA HETEROZYGOTES

Through sequencing of amplified DNA containing the appropriate alpha-g lobin genes we have identified the base substitution leading to the fo rmation of Hb G-Philadelphia [(alpha 68(E17)Asn Lys]. Three subjects ( similar to 25% Hb G) had an AAC AAA change at codon 68 of the alpha 2- globin gene; the chromosome with this mutation carried two alpha genes (alpha alpha). Six subjects (similar to 33% Hb G) had an AAC AAG chan ge at the same codon of the alpha 2 alpha 1 hybrid gene on a chromosom e with the 3.7 kb deletion (-alpha(3.7)). These results indicate two i ndependent mutations which likely occurred in different populations; i ncrease in the level of Hb G is primarily dependent upon the loss of o ne or more alpha-globin genes. (C) 1994 Wiley-Liss, Inc.