PDF(Pubmed)
Abstract：
OBJECTIVE: To report genetic characteristics and associated risk of chromosomal breaks due to chromosomal rearrangements in large samples.
METHODS: MicroSeq, a technique that combines chromosome microdissection and next-generation sequencing, was used to identify chromosomal breakpoints. Long-range PCR and Sanger sequencing were used to precisely characterize 100 breakpoints in 50 ABCR carriers.
RESULTS: In addition to the recurrent regions of balanced rearrangement breaks in 8q24.13, 11q11.23, and 22q11.21 that had been documented, we have discovered a 10-Mb region of 12q24.13-q24.3 that could potentially be a sparse region of balanced rearrangement breaks. We found that 898 breakpoints caused gene disruption and a total of 188 breakpoints interrupted genes recorded in OMIM. The percentage of breakpoints that disrupted autosomal dominant genes recorded in OMIM was 25.53% (48/188). Fifty-four of the precisely characterized breakpoints had 1-8-bp microhomologous sequences.
CONCLUSIONS: Our findings provide a reference for the evaluation of the pathogenicity of mutations in related genes that cause protein truncation in clinical practice. According to the characteristics of breakpoints, non-homologous end joining and microhomology-mediated break-induced replication may be the main mechanism for ABCRs formation.
METHODS: MicroSeq, a technique that combines chromosome microdissection and next-generation sequencing, was used to identify chromosomal breakpoints. Long-range PCR and Sanger sequencing were used to precisely characterize 100 breakpoints in 50 ABCR carriers.
RESULTS: In addition to the recurrent regions of balanced rearrangement breaks in 8q24.13, 11q11.23, and 22q11.21 that had been documented, we have discovered a 10-Mb region of 12q24.13-q24.3 that could potentially be a sparse region of balanced rearrangement breaks. We found that 898 breakpoints caused gene disruption and a total of 188 breakpoints interrupted genes recorded in OMIM. The percentage of breakpoints that disrupted autosomal dominant genes recorded in OMIM was 25.53% (48/188). Fifty-four of the precisely characterized breakpoints had 1-8-bp microhomologous sequences.
CONCLUSIONS: Our findings provide a reference for the evaluation of the pathogenicity of mutations in related genes that cause protein truncation in clinical practice. According to the characteristics of breakpoints, non-homologous end joining and microhomology-mediated break-induced replication may be the main mechanism for ABCRs formation.
摘要：
目的：报告大样本中染色体重排导致染色体断裂的遗传特征和相关风险。
方法：MicroSeq，一种结合染色体显微切割和下一代测序的技术，用于识别染色体断点。使用长程PCR和Sanger测序来精确表征50个ABCR载体中的100个断点。
结果：除了已记录的8q24.13、11q11.23和22q11.21中平衡重排断裂的重复区域外，我们发现了12q24.13-q24.3的10-Mb区域，该区域可能是平衡重排断裂的稀疏区域。我们发现在OMIM中记录的898个断点导致基因破坏,并且总共188个断点中断基因。OMIM中记录的破坏常染色体显性基因的断点百分比为25.53%(48/188)。精确表征的断点中有54个具有1-8bp的微同源序列。
结论：我们的发现为临床上评价引起蛋白质截短的相关基因突变的致病性提供了参考。根据断点的特点,非同源末端连接和微同源介导的断裂诱导的复制可能是ABCRs形成的主要机制。
方法：MicroSeq，一种结合染色体显微切割和下一代测序的技术，用于识别染色体断点。使用长程PCR和Sanger测序来精确表征50个ABCR载体中的100个断点。
结果：除了已记录的8q24.13、11q11.23和22q11.21中平衡重排断裂的重复区域外，我们发现了12q24.13-q24.3的10-Mb区域，该区域可能是平衡重排断裂的稀疏区域。我们发现在OMIM中记录的898个断点导致基因破坏,并且总共188个断点中断基因。OMIM中记录的破坏常染色体显性基因的断点百分比为25.53%(48/188)。精确表征的断点中有54个具有1-8bp的微同源序列。
结论：我们的发现为临床上评价引起蛋白质截短的相关基因突变的致病性提供了参考。根据断点的特点,非同源末端连接和微同源介导的断裂诱导的复制可能是ABCRs形成的主要机制。
