Blonden L A, Grootscholten P M, den Dunnen J T, Bakker E, Abbs S, Bobrow M, Boehm C, van Broeckhoven C, Baumbach L, Chamberlain J
Department of Human Genetics, Sylvius Laboratory, Leiden, The Netherlands.
Genomics. 1991 Jul;10(3):631-9. doi: 10.1016/0888-7543(91)90445-k.
Using whole cosmids as probes, we have mapped 242 DMD/BMD deletion breakpoints located in the major deletion hot spot of the DMD gene. Of these, 113 breakpoints were mapped more precisely to individual restriction enzyme fragments in the distal 80 kb of the 170-kb intron 44. An additional 12 breakpoints are distributed over the entire region, with no significant local variation in frequency. Furthermore, deletion sizes vary and are not influenced by the positions of the breakpoints. This argues against a predominant role of one or a few specific sequences in causing frequent rearrangements. It suggests that structural characteristics or a more widespread recombinogenic sequence makes this region so susceptible to deletion. Our study revealed several RFLPs, one of which is a 300-bp insertion/deletion polymorphism. Abnormally migrating junction fragments are found in 81% of the precisely mapped deletions and are highly valuable in the diagnosis of carrier females.
我们使用完整的黏粒作为探针，对位于杜氏肌营养不良症（DMD）基因主要缺失热点区域的242个DMD/贝克型肌营养不良症（BMD）缺失断点进行了定位。其中，113个断点被更精确地定位到170kb的内含子44远端80kb区域内的各个限制性酶切片段上。另外12个断点分布在整个区域，频率上无明显局部差异。此外，缺失大小各异，不受断点位置的影响。这表明，并非一个或几个特定序列在频繁重排中起主要作用。这表明该区域的结构特征或更广泛的重组序列使其如此容易发生缺失。我们的研究发现了几种限制性片段长度多态性（RFLP），其中一种是300bp的插入/缺失多态性。在81%的精确定位缺失中发现了异常迁移的连接片段，这对携带者女性的诊断非常有价值。
