TGGE AND HIEF - A COMPARISON OF 2 METHODS IN THE DETECTION OF CARRIERS OF THE Z-MUTATION OF THE ALPHA-1-ANTITRYPSIN GENE

Alpha-1-antitrypsin (alpha-1-AT) deficiency can lead to juvenile liver cirrhosis and lung emphysema in adulthood. The deficiency Z allele is caused by a base transition. Temperature gradient gel electrophoresis (TGGE) and hybrid isoelectric focusing (HIEF) were used to detect car riers of the Z mutation of the alpha-1-AT gene. The resulting data wer e compared. To verify carriers at the sequence level, a manual nonradi oactive sequencing strategy was established. Among our sample of carri ers of the Z mutation, two were not detected by HIEF that could be ide ntified by TGGE. DNA of all TGGE identified individuals harboring the Z mutation of the alpha-1-AT gene were sequenced nonradioactively. All carriers harbored a G to A transition at position 11.940. This mutati on is described to cause the altered protein.