Molecular basis for subtypic differences of the “a” subunit of coagulation factor XIII with description of the genesis of the subtypes

摘要

The “a” subunit of human coagulation factor XIII (F13A) exhibits genetic polymorphism defined by four common alleles,F13A*1A, *1B, *2A, and*2B.We have previously suggested on the basis of the isoelectric focusing patterns of the four allele products that point mutations at two separate sites and one intragenic crossing over might be involved in the genes of F13A polymorphism. Here, we report nucleotide substitutions associated with F13A polymorphism. A C/T transition of the second nucelotide of codon 564 in exon 12 is responsible for the difference betweenF13A*1Aand*1Band that between F13A*2A and *2B, and a set of two base changes in codons 650 and 651 in exon 14 leads to the differences betweenF13A*1Aand*2Aand those betweenF13A*1Band*2B. The four combinations of the point mutations at the two exons thus correspond to the four alleles, two of which were generated by the point mutations from ancestral monomorphic gene. The results suggest strongly that intragenic crossing over must be involved in the genesis of the fourth allele. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods discriminating these base changes in exons 12 and 14 are also presen