五、总结

除上述应用外，基因组检测技术也被广泛应用于肿瘤的诊断和靶向治疗的选择。例如通过检测肺癌患者的肿瘤组织中是否携带 EGFR 或 K-ras 的基因突变、是否存在 ALK-EML4 融合基因等，以此对患者的治疗方案进行指导。研究显示，与常规化疗相比，对携带特异性突变的患者进行靶向治疗可将患者的无进展中位生存期提高8~10个月。

在病原微生物的发现上，宏基因组的基因组检测技术在新冠病毒的发现和鉴定中起到了关键作用。复旦大学张永振团队首先从一名患者的肺泡灌洗液样本中提取到病毒，利用宏转录组测序技术准确地测定了病毒的全基因组序列，上传到GenBank，并指出了它和SARS病毒的相似度 ^［22］ ，随后中国疾病预防控制中心谭文杰团队分析了病毒的变异位点和进化树 ^［23］ 。我国科研单位对于新冠病毒的迅速发现与测序是后续开发快速、有效的核酸检测试剂盒的基础，是对患者准确诊断和有效控制疫情的基础，得到了各国政府和WHO的高度评价。

总而言之，应用基因检测技术，我们进行了疾病致病基因的定位，实现了临床遗传病早期诊断，指导了特异性的药物开发，并进行着精准的个体化用药指导。可以说，基因检测在精准医学中发挥着不可或缺的作用。

参考文献

［1］翟中和，王喜忠，丁明孝.细胞生物学（第3版）［M］.北京：高等教育出版社，2007.

［2］Pennisi E. Genomics. ENCODE project writes eulogy for junk DNA［J］. Science, 2012,337(6099):1159,1161.

［3］de Koning A P, Gu W, Castoe T A, et al. Repetitive elements may comprise over two-thirds of the human genome［J］. PLoS Genetics, 2011,7(12): e1002384.

［4］Zarrei M, MacDonald J R, Merico D, et al. A copy number variation map of the human genome［J］. Nature Reviews Genetics, 2015,16(3):172-183.

［5］Bird A. Perceptions of epigenetics［J］. Nature, 2007,447(7143):396-398.

［6］Maelicke A. Genomics and postgenomics［J］. Nachrichten Aus Der Chemie, 2000,48(6):793795.

［7］黄树嘉.测序技术发展历程. https://www.jianshu.com/p/6122cecec54a. 2017.

［8］Sanger F, Coulson A R. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase［J］. Journal of Molecular Biology, 1975,94(3):441-448.

［9］Mardis E R. DNA sequencing technologies: 2006-2016［J］. Nature Protocols, 2017,12(2):213218.

［10］杨金水.基因组学（第4版）［M］.北京：高等教育出版社，2019.

［11］Maxam A M, Gilbert W. A new method for sequencing DNA［J］. PNAS, 1977,74(2):560-564.

［12］Goodwin S, McPherson J D, McCombie W R. Coming of age: ten years of next-generation sequencing technologies［J］. Nature Reviews Genetics, 2016,17(6):333-351.

［13］Margulies M, Egholm A, Altman W E, et al. Genome sequencing in microfabricated high-density picolitre reactors［J］. Nature, 2005,437(7057):376-380.

［14］Shendure J, Porreca G J, Reppas N B, et al. Accurate multiplex polony sequencing of an evolved bacterial genome［J］. Science, 2005,309(5741):1728-1732.

［15］Guo J, Xu N, Li Z, et al. Four-color DNA sequencing with 3'-O-modified nucleotide reversible terminators and chemically cleavable fluorescent dideoxynucleotides［J］. PNAS, 2008,105(27):9145-9150.

［16］DMLapato. Cluster Generation［EB］.2015. https://commons. wikimedia. org/wiki/File: cluster_Generation.png.

［17］Rothberg J M, Hinz W, Rearick T M, et al. An integrated semiconductor device enabling nonoptical genome sequencing. Nature, 2011,475(7356):348-352.

［18］生信小撰.二代测序的比对算法浅析［EB］.2019. https://zhuanlan.zhihu.com/p/66910669.

［19］Dervan A, Shendure J. Chapter 3: The State of Whole-Genome Sequencing［M］// Ginsburg G S, Willard H F. Genomic and Precision Medicine (Third Edition). Boston: Academic Press,2017,45-62.

［20］Katsanis S H, Katsanis N. Molecular genetic testing and the future of clinical genomics［J］.Nature Reviews Genetics, 2013,14(6):415-426.

［21］Noor N, Shapira A, Edri R, et al. 3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts［J］. Advanced Science, 2019.6(11):1900344.

［22］Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China［J］. Nature, 2020,579(7798):265-269.

［23］Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding［J］. Lancet, 2020,395(10224):565574.

（怀聪，孙一丹，王卓，乔中东，师咏勇） wi7OOBRlPPvBF5Iil0PPi8e4fNfUHQWiBNqUj3uJwk9AJLPpPnfnxTsAQf0kFw5U