Chromosome jumping from D4S10 (G8) toward the Huntington disease gene.
Chromosome jumping from D4S10 (G8) toward the Huntington disease gene.
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染色体从 D4S10 (G8) 跳跃到亨廷顿病基因。
DOI：
10.1073/pnas.85.17.6437
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发表时间：
1988
影响因子：
11.1
通讯作者：
Collins,FS
中科院分区：
文献类型：
--
作者：
Richards,JE;Gilliam,TC;Cole,JL;Drumm,ML;Wasmuth,JJ;Gusella,JF;Collins,FS
通过连锁分析，亨廷顿病（HD）的基因已定位于人类4号染色体短臂的远端部分。目前，两个最接近的DNA标记是D4 S10（G8），位于距HD着丝粒约3厘摩的位置，以及D4 S43（C4 H），位于距HD 0-1.5厘摩的位置。为了更接近HD基因，最终目标是识别基因本身，我们将染色体跳跃技术应用于该区域。构建了200千碱基的跳跃库，获得了从D4 S10的跳跃，并通过脉冲场凝胶电泳验证了其大致距离。两个限制性片段长度多态性已被确定在跳跃基因座，这是表示D4 S81。先前鉴定的D4 S10和HD或D4 S10和D4 S43之间的重组体的连锁分析显示，在五个事件中的两个中，跳跃已经越过重组点。这明确定位了D4 S10和D4 S81在染色体上的位置，为HD提供了额外的标记，并表明4号染色体这一区域的重组频率可能增加，因此D4 S10与HD的物理距离可能没有最初怀疑的那么大。
The gene for Huntington disease (HD) has been localized to the distal portion of the short arm of human chromosome 4 by linkage analysis. Currently, the two closest DNA markers are D4S10 (G8), located approximately equal to 3 centimorgans centromeric to HD, and D4S43 (C4H), positioned 0-1.5 centimorgans from HD. In an effort to move closer to the HD gene, with the eventual goal of identifying the gene itself, we have applied the technique of chromosome jumping to this region. A 200-kilobase jumping library has been constructed, and a jump from D4S10 has been obtained and its approximate distance verified by pulsed field gel electrophoresis. Two restriction fragment length polymorphisms have been identified at the jump locus, which is denoted D4S81. Linkage analysis of previously identified recombinants between D4S10 and HD or D4S10 and D4S43 shows that in two of five events the jump has crossed the recombination points. This unequivocally orients D4S10 and D4S81 on the chromosome, provides additional markers for HD, and suggests that recombination frequency in this region of chromosome 4 may be increased, so that the physical distance from D4S10 to HD may not be as large as originally suspected.