应用第三代测序技术检测Y连锁遗传性耳聋家系的复杂重组结构研究  

Application of Third-Generation Sequencing Technique in Studying the Complex Recombination Structure in the Y-linked Hereditary Deafness Pedigree

作　　者：吴萧男 关静[1] 兰兰[1] 王洪阳[1] 王大勇[1] 王秋菊[1] WU Xiaonan;GUAN Jing;LAN Lan;WANG Hongyang;WANG Dayong;WANG Qiuju(Department of Audiology and Vestibular Medicine,Senior Department of Otolaryngology Head and Neck Surgery,Chinese PLA General Hospital.Medical School of Chinese PLA.National Clinical Research Center for Otolaryngologic Diseases.Key Lab of Hearing Science,Ministry of Education.Chinese PLA Institute of Otolaryngology,Beijing 100853,China)

机构地区：[1]解放军总医院耳鼻咽喉头颈外科医学部耳鼻咽喉内科,解放军医学院,国家耳鼻咽喉疾病临床医学研究中心,聋病教育部重点实验室,解放军耳鼻咽喉研究所,北京100853

出　　处：《中华耳科学杂志》2022年第2期205-210,共6页Chinese Journal of Otology

基　　金：国家自然科学基金重点项目(81830028),国家自然科学基金面上项目(82171130),国家自然科学基金青年项目(81900951,81900950)联合资助~~。

摘　　要：目的 研究Y连锁遗传性耳聋家系患者的Y染色体上存在的复杂重组结构的插入片段及断点。方法应用第三代测序技术中的Nanopore技术,对Y连锁遗传性耳聋家系中1名先证者及家系外正常男性进行测序,并将测序结果对比分析,研究此复杂重组结构各插入片段在正常男性中的存在情况。结果 通过Nanopore技术检测,发现先证者Y染色体Yp11.2区存在一段长约793kb的复杂重组结构,由9段1号染色体及Y染色体不相连片段组成。通过对比分析,证明在正常男性中不存在此复杂重组结构。结论 第三代测序技术能够凭借其长读长的特点跨越染色体重复区域断点,对Y染色体的复杂拷贝数变异区域进行测序。Objective To study inserted fragments and breakpoints in the complex recombination structure of the Y chromosome in the Y linked hereditary deafness pedigree. Methods The proband in the pedigree of Y linked hereditary deafness and its normal males were sequenced using the Nanopore technique of the Third Generation Sequencing technology. The sequencing results were compared and analyzed to determine whether the same complex recombination structure existed in normal males. Results A complex recombination structure of about 793kb was found on the Yp11.2region of the Y chromosome in the proband by the Nanopore technique. The complex recombination structure was composed of 9 segments from chromosome 1 and the Y chromosome, respectively, and did not exist in normal males by comparative analysis. Conclusion With its characteristic long reading length, the Third Generation Sequencing technology can cross breakpoints in chromosome duplication regions and thus be used to sequence complex copy number variation regions in the Y chromosome.

关 键 词：Y染色体 遗传性耳聋 第三代测序技术 拷贝数变异 

分 类 号：R764[医药卫生—耳鼻咽喉科]