Two different mutations in codon 68 are observed in Hb G‐Philadelphia heterozygotes

Through sequencing of amplified DNA containing the appropriate α‐giobin genes we have identified the base substitution leading to the formation of Hb G‐Philadelphia [α6B(El7)Asn Lys]. Three subjects (∼25% Hb G) had an AAC AAA change at codon 68 of the α2‐globin gene; the chromosome with this mutation carried two α genes (αα). Six subjects (∼33% Hb G) had an AAC AAG change at the same codon of the α2α1 hybrid gene on a chromosome with the 3.7 kb deletion (‐α 3.7 ). These results indicate two inde pendent mutations which likely occurred in different populations; Increase In the level of Hb G is primarily dependent upon the loss of one or more α‐globin genes. © 1994 Wiley‐Liss, Inc.