Purrello M, Alhadeff B, Esposito D, Szabo P, Rocchi M, Truett M, Masiarz F, Siniscalco M
EMBO J. 1985 Mar;4(3):725-9. doi: 10.1002/j.1460-2075.1985.tb03689.x.
Two DNA recombinant clones, shown by separate studies to contain DNA sequences homologous to the genes coding for the human blood coagulation Factors VIII and IX, were hybridized in situ to metaphases or prometaphases derived from patients with the fragile-X syndrome and from a normal control. The results of these experiments indicate that (i) both genes are located in the subtelomeric region of the long arm of the human X chromosome flanking the fragile site at Xq27.3, (ii) the resolution of this localization is approximately 0.5% the length of the human haploid genome, i.e., 1.8 X 10(7) bp, (iii) the linear order of loci within the above region is Factor IX-fragile site-Factor VIII-Xqter. Both the localization and the linear order of these loci have been confirmed by Southern blotting studies using the same molecular probes and a panel of rodent-human somatic cell hybrids known to have retained different segments of the human X chromosome. The findings described herein and the knowledge that Factor IX deficiency recombines freely with at least two loci of the G6PD cluster support our hypothesis that the chromosomal region which includes the fragile-X site is normally a region of high meiotic recombination.
通过单独研究显示含有与编码人类凝血因子VIII和IX的基因同源的DNA序列的两个DNA重组克隆,与来自脆性X综合征患者和正常对照的中期或早中期进行原位杂交。这些实验结果表明:(i)这两个基因都位于人类X染色体长臂的亚端粒区域,位于Xq27.3的脆性位点两侧;(ii)这种定位的分辨率约为人类单倍体基因组长度的0.5%,即1.8×10⁷bp;(iii)上述区域内基因座的线性顺序是因子IX - 脆性位点 - 因子VIII - Xqter。这些基因座的定位和线性顺序均已通过使用相同分子探针以及一组已知保留了人类X染色体不同片段的啮齿动物 - 人类体细胞杂种进行的Southern印迹研究得到证实。本文所述的发现以及因子IX缺乏与G6PD簇的至少两个基因座自由重组的知识支持了我们的假设,即包括脆性X位点的染色体区域通常是减数分裂重组率高的区域。