FACTOR-VIII GENE INVERSIONS CAUSING SEVERE HEMOPHILIA-A ORIGINATE ALMOST EXCLUSIVELY IN MALE GERM-CELLS
FACTOR-VIII GENE INVERSIONS CAUSING SEVERE HEMOPHILIA-A ORIGINATE ALMOST EXCLUSIVELY IN MALE GERM-CELLS
复制标题
DOI：
10.1093/hmg/3.7.1035
复制
发表时间：
1994-07-01
影响因子：
3.5
通讯作者：
ANTONARAKIS, SE
中科院分区：
文献类型：
--
作者：
ROSSITER, JP;YOUNG, M;ANTONARAKIS, SE
血友病A中有缺陷的凝血因子VIII基因位于X染色体长臂的最后一个兆位。由于位于基因内含子22内的基因A的错配拷贝与其端粒的约500 kb之间的染色体内同源重组引起的倒位占所有重度血友病A病例的近一半。我们假设Xq与其同源物的配对抑制了倒位过程，因此，该事件主要起源于雄性生殖细胞。在所有20个信息的情况下，倒位起源于外祖父母，DNA多态性分析确定它发生在男性生殖系。此外，50名因倒位而出现散发病例的母亲中，除一人外，其余均为携带者。因此，这些数据支持这一假设，并表明导致重度血友病A的因子VIII基因倒位几乎仅发生在男性生殖细胞中。
The factor VIII gene, which is defective in hemophilia A, is located in the last megabase of the long arm of the X chromosome. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomeric to it account for nearly half of all cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the inversion process, and that, therefore, the event originates predominantly in male germ cells. In all 20 informative cases in which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but one of 50 mothers of sporadic cases due to an inversion were carriers. Thus, these data support the hypothesis and indicate that factor VIII gene inversions leading to severe hemophilia A occur almost exclusively in male germ cells.