Hot spot for genetic recombination in the coagulation factor XIII a subunit gene

点击翻译按钮获取中文摘要

We have disclosed sequence heterogeneities in the coding regions of the human coagulation factor XIII a subunit (F13A) gene. F13A protein shows genetic polymorphism detected by isoelectric focusing. Polymorphism of F13A is defined by nucleotide substitutions in exons 12 and 14. The sequence heterogeneities were shown to result from synonymous substitutions in exons 8 and 12 and from nonsymous but neutral amino acid substitutions encoded by nucleotides in exons 2 and 5. These polymorphic sites are inherited as sequence haplotypes, the expected number of which is estimated at 72 combinations. Screening for such haplotypes demonstrated 18 different types in Caucasian populations. Interestingly, the combination of those polymorphic sites are equilibrated, the findings of which suggested frequent exchange of the sites between preexisting haplotypes.We defined a de nove recombinant gene at the ABO blood group locus and showed polymorphic occurrence of such recombinant alleles in a Japanese population. Further characterization of one recombinant allele demonstrated gene conversion-like event underlay the generation of such recombinant alleles. Screening a German population for such alleles showed no recombinants, which fact suggests that there are ethnic differences in unknown regions involved in the recombination at the ABO locus.Recombination hot spots have been reported at many loci in human genome but direct evidences, such as specific for recombination, have not been elucidated thus far. Characterization of the de novo recombinant at the ABO locus will open the way to clarify mechanisms of crossing over or gene conversion in human.