Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4.
Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4.
复制标题
D4S98/S114/S113 的映射将亨廷顿舞蹈症缺陷限制在 4 号染色体端粒处的一个缩小的物理区域。
DOI：
10.1093/nar/16.24.11769
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发表时间：
1988
影响因子：
14.9
通讯作者：
Gilliam,TC
中科院分区：
文献类型：
--
作者：
Whaley,WL;Michiels,F;MacDonald,ME;Romano,D;Zimmer,M;Smith,B;Leavitt,J;Bucan,M;Haines,JL;Gilliam,TC
亨廷顿病（HD）的显性基因缺陷与DNA标记D4 S10有关，D4 S10位于4号染色体短臂的端粒附近，另外两个标记D4 S43和D4 S95更接近HD基因，但仍位于4p16.32。通过克隆NotI基因片段的末端，我们鉴定了一个新的基因座D4 S114，通过物理和遗传作图技术，将其定位于D4 S43和D4 S95的远端。“末端”克隆与先前分离的NotI“连接”克隆重叠，并且在定义D4 S113的第二个“连接”克隆的150 kb内。D4 S113和D4 S114的限制性片段长度多态性，其中之一与匿名探针pB 5731 B-C（D4 S98）检测到的SacI多态性相同，被分型为HD和参考家系中的关键交叉。支持D_4S_10-（D_4S_43，D_4S_98，D_4S_95）-D_4S_98/S_114/S_113-HD-telemere的位点顺序。因此，D4 S98/S114/S113簇代表了与HD最近的克隆序列，并为启动定向克隆策略以分离和鉴定该疾病基因提供了有价值的新点。
The dominant gene defect in Huntington's disease (HD) is linked to the DNA marker D4S10, near the telomere of the chromosome 4 short arm. Two other markers,D4S43andD4S95, are closer, but still proximal to theHDgene in 4p16.32. We have characterized a new locus,D4S114, identified by cloning the end of a NotI fragment resolved by pulsed-field gel electrophoresis.D4S114was localized distal toD4S43andD4S95by both physical and genetic mapping techniques. The ‘end’-clone overlaps a previously isolated NotI ‘linking’ clone, and is within 150 kb of a second ‘linking’ clone definingD4S113. Restriction fragment length polymorphisms forD4S113andD4S114, one of which is identical to a SacI polymorphism detected by the anonymous probe pB5731B-C (D4S98), were typed for key crossovers in HD and reference pedigrees. The data support the locus orderD4S10-(D4S43, D4S98, D4S95)-D4S98/S114/S113-HD-telemere. TheD4S98/S114/S113cluster therefore represents the nearest cloned sequences toHD, and provides a valuable new point for launching directional cloning strategies to isolate and characterize this disease gene.