染色体平衡易位是一种常见的染色体异常重组，常引起发育异常、流产、不孕不育等，但目前其发生原因及机制不清。结合文献报道和我们的前期研究发现：平衡易位断裂重组位点多数位于具有转录特性的基因编码区，而转录可通过与复制叉相撞，干扰复制延伸导致基因组不稳定性的产生。据此我们提出假设：转录复制相撞所致基因组不稳定性是介导平衡易位产生的重要原因。为此，我们拟采用CRISPR/Cas9基因打靶系统构建人基因组内源性基因转录复制相撞模型，进而通过体外CRISPR酶切体系，获得打靶基因完整片段，检测其分子量及构象变化得到转录干扰复制的直接证据；最后通过相关重组通路和重组类型的检测，证实转录复制相撞能够导致平衡易位的产生，为深入探讨两者间的关联及机制，以及转录复制相撞在相关疾病发生中的作用奠定基础。

Chromosomal balanced translocation (CBT) is a common chromosomal structural variation, which associated with abnormal development, abortion and infertility, but until now, the causes of CBT are still unknown. Previous studies and our experiment found that most CBT breakpoints locate in genes which get the feature of transcription. Transcription has been reported to induce genome instability through collision with replication by disturb the replicate extension, so we hypothesize the genome instability caused by collision of transcription and replication is a major cause of CBT. To verify the hypothesis, we plan to construct an endogenous TRC model in human cell line by CRISPR/Cas9 system, and use in vitro CRISPR enzyme digest system to get the full gene fragment to obtain the direct evidence of transcription-replication collision, then through detecting the type and passway of recombination to uncover the relationship and mechanism between TRC and CBT, and expect to provide theoretical basis in prevention and treatment of the CBT related diseases.