Monaco A P, Bertelson C J, Middlesworth W, Colletti C A, Aldridge J, Fischbeck K H, Bartlett R, Pericak-Vance M A, Roses A D, Kunkel L M
Nature. 1985;316(6031):842-5. doi: 10.1038/316842a0.
The Duchenne muscular dystrophy (DMD) locus has been localized to the short arm of the human X chromosome (Xp21) by detection of structural abnormalities and by genetic linkage studies. A library highly enriched for human DNA from Xp21 was constructed using DNA isolated from a male patient who had a visible deletion and three X-linked disorders (DMD, retinitis pigmentosa and chronic granulomatous disease). Seven cloned DNA probes from this library and the probe 754 (refs 5, 8) are used in the present study to screen for deletions in the DNA isolated from 57 unrelated males with DMD. Five of these DMD males are shown to exhibit deletions for one of the cloned DNA segments and at least 38 kb of surrounding DNA. In addition, two subclones from the same region detect four restriction fragment length polymorphisms which exhibit no obligate recombination with DMD in 34 meiotic events. These new DNA segments will complement the existing Xp21 probes for use in carrier detection and prenatal diagnosis of DMD. Elucidation of the end points of the five deletions will help delineate the extent of the DMD locus and ultimately lead to an understanding of the specific sequences involved in DMD.
通过检测结构异常和进行基因连锁研究，杜氏肌营养不良症（DMD）基因座已被定位到人类X染色体的短臂（Xp21）上。利用从一名患有可见缺失及三种X连锁疾病（DMD、色素性视网膜炎和慢性肉芽肿病）的男性患者分离出的DNA，构建了一个高度富集Xp21人类DNA的文库。本研究使用了来自该文库的七个克隆DNA探针以及探针754（参考文献5、8），对从57名无关的DMD男性中分离出的DNA进行缺失筛选。这些DMD男性中有五名被证明在其中一个克隆DNA片段以及至少38 kb的周边DNA上存在缺失。此外，来自同一区域的两个亚克隆检测到四个限制性片段长度多态性，在34次减数分裂事件中，这些多态性与DMD没有必然的重组。这些新的DNA片段将补充现有的Xp21探针，用于DMD携带者检测和产前诊断。阐明这五个缺失的端点将有助于描绘DMD基因座的范围，并最终有助于了解与DMD相关的特定序列。
