Pericentromeric organization at the fusion point of mouse Robertsonian translocation chromosomes
Pericentromeric organization at the fusion point of mouse Robertsonian translocation chromosomes
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DOI：
10.1073/pnas.98.1.171
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发表时间：
2001-01-02
影响因子：
11.1
通讯作者：
Redi, CA
中科院分区：
文献类型：
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作者：
Garagna, S;Marziliano, N;Redi, CA
在哺乳动物中，罗伯逊易位（两个端着丝粒/近端着丝粒染色体在着丝粒处连接形成一个中着丝粒）是染色体进化中导致物种形成的最有效过程;它的发生也影响人类健康（通过诱导三体）和家畜的生育力。为了解Rb易位的机制，我们以家鼠为模型，研究了端着丝粒体和Rb染色体的近着丝粒卫星DNA（satDNA）的组织结构，包括小卫星DNA和大卫星DNA。用染色体定位荧光原位杂交（CO-FISH）技术分析了大卫星DNA。开发了将GO-FISH与引发的原位标记和常规FISH相结合的方法，其灵敏度比单独的GO-FISH方法高五倍。结果表明，在端着丝粒染色体和Rb染色体上，satDNA串联重复序列的大小都是首尾相连的，相对于着丝粒的极性总是相同的。我们认为，一个物种中所有串联重复的satDNAs可能都被锁定在这样一个对称约束中，这是染色体进化的普遍结果。Rb易位断裂点被发现定位在端着丝粒的小satDNA，这些序列对称的Rb染色体的着丝粒区域的形成作出贡献。这些结果是重要的Rb易位的几何形状的理解，并建议作为一种新的工具，调查这些重排的DNA方向的研究。
In mammals, Robertsonian (Rb) translocation (the joining of two telo/acrocentric chromosomes at their centromere to form a metacentric) is the most effective process in chromosomal evolution leading to speciation; its occurrence also affects human health (through the induction of trisomies) and the fertility of farm animals. To understand the mechanism of Rb translocation, we used the house mouse as a model system and studied the organization of pericentromeric satellite DNAs (satDNA) of telocentrics and Rb chromosomes, both minor and major satDNA, The chromosome-orientation fluorescence in situ hybridization (CO-FISH) technique was used to analyze the major satDNA, To detect the very small amount of minor satDNA, a procedure was developed that combines GO-FISH with primed in situ labeling and conventional FISH and is five times more sensitive than the GO-FISH procedure alone. It was found that both the major and the minor satDNA tandem repeats are oriented head-to-tail in telocentric and Rb chromosomes, and their polarity is always the same relative to the centromere. We suggest that all tandemly repetitive satDNAs in a species probably are locked into such a symmetry constraint as a universal consequence of chromosomal evolution. Rb translocation breakpoints were found localized within the minor satDNA of telocentrics, and these sequences contributed symmetrically to the formation of the centromeric region of the Rb chromosomes. These results are important for an understanding of the geometry of Rb translocations and suggest the study of DNA orientation as a new tool for investigating these rearrangements.