ANALYSIS OF THE TANDEM REPEAT LOCUS D4Z4 ASSOCIATED WITH FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY
ANALYSIS OF THE TANDEM REPEAT LOCUS D4Z4 ASSOCIATED WITH FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY
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DOI：
10.1093/hmg/3.8.1287
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发表时间：
1994-08-01
影响因子：
3.5
通讯作者：
WILLIAMSON, R
中科院分区：
文献类型：
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作者：
HEWITT, JE;LYLE, R;WILLIAMSON, R
与面肩肱骨肌营养不良症（FSHD）相关的串联重复序列（D4Z4）的序列已经确定：3.3 kb重复序列的每个拷贝包含两个同源盒和两个先前描述的重复序列，LSau和一个富含gc的低拷贝重复序列，指定为hhspm3。通过Southern blotting、FISH以及cDNA和基因组克隆的分离，我们发现在人类基因组的其他位置存在与D4Z4相似的重复序列。灵长类基因组DNA的Southern blot分析表明，d4z4样重复序列的拷贝数在过去的2500万年中显著增加。分离出两个cDNA克隆，发现在同源结构域内含有停止密码子和帧移。对dna产生STS，对体细胞杂交面板的分析表明它们映射到14号染色体。没有cDNA克隆映射到染色体4q35 D4Z4重复，它们编码蛋白质的可能性不能排除。虽然D4Z4可能不编码蛋白质，但该位点的缺失与FSHD之间存在关联。D4Z4重复序列包含LSau重复序列，与68 bp的Sau3A重复序列相邻。这两个序列都与DNA的异色区有关，这些区域已知与位置效应变异现象有关。我们假设D4Z4序列的缺失会产生位置效应。
The sequence of the tandem repeat sequence (D4Z4) associated with facioscapulohumeral muscular dystrophy (FSHD) has been determined: each copy of the 3.3 kb repeat contains two homeoboxes and two previously described repetitive sequences, LSau and a GC-rich low copy repeat designated hhspm3. By Southern blotting, FISH and isolation of cDNA and genomic clones we show that there are repeat sequences similar to D4Z4 at other locations in the human genome. Southern blot analysis of primate genomic DNA indicates that the copy number of D4Z4-like repeats has increased markedly within the last 25 million years. Two cDNA clones were isolated and found to contain stop codons and frameshifts within the homeodomains. An STS was produced to the cDNAs and analysis of a somatic cell hybrid panel suggests they map to chromosome 14. No cDNA clones mapping to the chromosome 4q35 D4Z4 repeats that they encode a protein cannot be ruled out. Although D4Z4 may not encode a protein, there is an association between deletions within this locus and FSHD. The D4Z4 repeats contain LSau repeats and are adjacent to 68 bp Sau3A repeats. Both of these sequences are associated with heterochromatic regions of DNA, regions known to be involved in the phenomenon of position effect variegation. We postulate that deletion of D4Z4 sequences could produce a position effect.