PDF(Pubmed)
Abstract：
Because the total gene copy number remains constant and all genes are normally expressed, carriers of balanced chromosomal translocations usually have a normal phenotype but are able to produce many different types of gametes during meiosis, and unbalanced gametes lead to increased risks of infertility, recurrent spontaneous abortion, stillbirth, neonatal death or malformations and intellectual abnormalities in offspring. The key to balanced translocations lies in finding the breakpoints, but current genetic testing techniques are all short-read sequencing, with the disadvantage of procedural complexity and imprecision for precisely identifying the breakpoints. The latest third-generation sequencing technology overcomes these drawbacks and uses robust long-read sequencing to accurately and rapidly detect genome-wide information and identify breakpoint locations. In this paper, we performed whole genome long-read sequencing using an Oxford Nanopore sequencer to detect the breakpoints of 4 balanced chromosomal translocation carriers. The results showed that employing about ~ 10× coverage confirmed 6 of the 8 breakpoints, of which, 2 had microdeletions/insertions identified near the breakpoints and 4 had breakpoints that disrupted the normal gene structure and were simultaneously tested for genome-wide structural variation (SV). The results show that whole genome long-read sequencing is an efficient method for pinpointing translocation breakpoints and providing genome-wide information, which is essential for medical genetics and preimplantation genetic testing.
摘要：
因为总基因拷贝数保持恒定，所有基因都正常表达，平衡染色体易位的携带者通常具有正常的表型，但能够在减数分裂期间产生许多不同类型的配子，配子不平衡导致不孕的风险增加，复发性自然流产,死产,新生儿死亡或后代畸形和智力异常。平衡易位的关键在于找到断点，但是目前的基因检测技术都是短读数测序，具有程序复杂和不精确的缺点，无法精确识别断点。最新的第三代测序技术克服了这些缺点，并使用强大的长读数测序来准确快速地检测全基因组信息并识别断点位置。在本文中,我们使用OxfordNanopore测序仪进行了全基因组长读测序,以检测4个平衡染色体易位载体的断点.结果表明，采用约10倍的覆盖率证实了8个断点中的6个，其中，2个具有在断点附近鉴定的微缺失/插入,4个具有破坏正常基因结构的断点,并且同时测试全基因组结构变异(SV)。结果表明，全基因组长读取测序是一种有效的方法，可以准确定位易位断点，提供全基因组信息，这对于医学遗传学和植入前遗传学测试至关重要。
