Weber B, Collins C, Kowbel D, Riess O, Hayden M R
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Genomics. 1991 Dec;11(4):1113-24. doi: 10.1016/0888-7543(91)90039-h.
The HD locus has been assigned to 4p16.3 distal to the DNA segment D4S10. However, the precise location of this gene is still unknown. At least three regions, together encompassing more than 3.5 Mb of DNA, can still be considered as candidate regions for the HD gene. Our efforts are directed toward the cloning and the complete characterization of one of these regions. Thus far we have cloned 460 kb of DNA in contiguously overlapping cosmids distal to D4S111 and have developed a detailed long-range restriction map orienting the contig within the terminal region of 4p16.3. We characterized 15 CpG-rich islands defined by tightly clustered rare cutter restriction sites for the enzymes NotI, BssHII, EagI, NruI, and SacII. In addition, we show that the sequences associated with the CpG-rich islands detect cross-species conservation. The detailed genetic analysis of the 460-kb contig provides a framework for the identification of genes, which can be assessed for the characteristics expected for the HD gene.
亨廷顿舞蹈病（HD）基因座已被定位于4号染色体短臂1区6带3亚带（4p16.3），位于DNA片段D4S10的远端。然而，该基因的确切位置仍不清楚。至少有三个区域，总共包含超过350万个碱基对（3.5 Mb）的DNA，仍可被视为HD基因的候选区域。我们致力于对其中一个区域进行克隆和完整的特征描述。到目前为止，我们已经在D4S111远端的黏粒中克隆了460千碱基对（460 kb）的连续重叠DNA，并绘制了详细的长程限制性图谱，确定了该重叠群在4p16.3末端区域内的方向。我们鉴定了15个富含CpG的岛，这些岛由限制性内切酶NotI、BssHII、EagI、NruI和SacII的紧密聚集的稀有切割位点定义。此外，我们还表明，与富含CpG的岛相关的序列具有跨物种保守性。对这个460 kb重叠群的详细遗传分析为基因鉴定提供了一个框架，这些基因可以根据HD基因预期的特征进行评估。
