Whaley W L, Bates G P, Novelletto A, Sedlacek Z, Cheng S, Romano D, Ormondroyd E, Allitto B, Lin C, Youngman S
Neurogenetics Laboratory, Massachusetts General Hospital, Boston 02114.
Somat Cell Mol Genet. 1991 Jan;17(1):83-91. doi: 10.1007/BF01233207.
Huntington's disease (HD) is tightly linked to genetic markers in 4p16.3. We have used a regional somatic cell hybrid mapping panel to isolate and map 25 cosmids to the proximal portion of 4p16.3 and 17 cosmids to the distal portion. The latter were positioned by long-range restriction mapping relative to previously mapped markers. One cosmid, L6 (D4S166), spans the critical breakpoint in the mapping panel that distinguishes proximal and distal 4p16.3. Four of the cosmids mapped distal to D4S90, the previous terminal marker on 4p, and stretched to within 75 kb of the telomere. Several of the cosmids that mapped between L6 and D4S90 were clustered near a number of previously isolated clones in a region with many NotI sites. Cosmid E4 (D4S168) was localized immediately proximal to the one remaining gap in the long-range restriction map of distal 4p16.3. Although pulsed field gel mapping with E4 failed to link the two segments of the map, the intervening gap was excluded as a potential site for the HD gene by genetic analysis.
亨廷顿舞蹈病（HD）与4p16.3区域的遗传标记紧密连锁。我们利用一个区域体细胞杂种定位板，将25个黏粒分离并定位到4p16.3的近端部分，17个黏粒定位到远端部分。后者通过相对于先前定位标记的长距离限制性图谱定位。一个黏粒L6（D4S166）跨越定位板中的关键断点，该断点区分了4p16.3的近端和远端。在4p上先前的末端标记D4S90远端定位的4个黏粒，延伸到距端粒75 kb范围内。在L6和D4S90之间定位的几个黏粒聚集在一个有许多NotI位点的区域中一些先前分离的克隆附近。黏粒E4（D4S168）定位在4p16.3远端长距离限制性图谱中剩下的一个间隙的紧邻近端位置。尽管用E4进行脉冲场凝胶图谱分析未能连接图谱的两个片段，但通过遗传分析排除了中间间隙作为HD基因潜在位点的可能性。
