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

我们已经公开了人凝血因子XIII a亚基（F13A）基因编码区的序列异质性。等电聚焦电泳显示F13A蛋白具有遗传多态性。F13A的多态性由外显子12和14中的核苷酸取代定义。序列的异质性被证明是由外显子8和12中的同义替换和外显子2和5中的核苷酸编码的非对称但中性的氨基酸替换引起的。这些多态性位点作为序列单倍型遗传，其预期数量估计为72种组合。对这些单倍型的筛选在高加索人群中显示出18种不同的类型。有趣的是，这些多态性位点的组合是平衡的，其结果表明，频繁的交换的网站之间预先存在的haplotype.We定义了一个新的重组基因在ABO血型基因座，并显示多态性的发生，这样的重组等位基因在日本人口。对一个重组等位基因的进一步表征证明了基因转化样事件导致了这种重组等位基因的产生。在德国人群中筛选这些等位基因没有发现重组体，这一事实表明，在ABO基因座上参与重组的未知区域存在种族差异。在人类基因组的许多基因座上已经报道了重组热点，但迄今为止尚未阐明直接的证据，如重组的特异性。在ABO基因座的从头重组的表征将打开的方式，以澄清在人类中的交叉或基因转换的机制。

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.