Allelic dimorphism in the human tissue-type plasminogen activator (TPA) gene as a result of an Alu insertion/deletion event.

Polymerase chain reaction and direct sequencing were used to investigate an amplified DNA fragment containing the suspected polymorphic site of all known intragenic restriction fragment length polymorphisms (RFLPs) within the human tissue-type plasminogen activator (TPA) gene. Sequence data obtained showed that these RFLPs were all generated by the presence or absence of one of the two Alu sequences located in intron h of the human TPA gene. Furthermore, one of the direct repeats flanking this Alu sequence was absent in the minor allele. In addition to indicating the presence of an Alu insertion in an ancestral human TPA gene, these findings suggest a slip-replication mechanism for the deletion of this Alu repeat, once inserted into the gene. As both alleles have been observed in similar frequencies among different ethnic groups, the insertion or subsequent deletion of this Alu sequence in the human TPA gene must have occurred early in human evolution.