【《染色体结构变异诱发小鼠耳聋的疾病模型研究文献综述》3200字】

染色体结构变异诱发小鼠耳聋的疾病模型研究文献综述随着小鼠全基因组测序工作的完成以及高通量测序技术的不断发展ADDINEN.CITEADDINEN.CITE.DATA(\o"Waterston,2002#2052"Waterstonetal.,2002)，遗传性听力损失相关的突变基因和突变类型也越来越丰富，除了基因发生SingleNucleotidePolymorphism（SNP）和Insertion-Deletion（InDel）突变导致小鼠耳聋的研究外ADDINEN.CITE<EndNote><Cite><Author>Zhang</Author><Year>2020</Year><RecNum>1968</RecNum><DisplayText>(Zhangetal.,2020)</DisplayText><record><rec-number>1968</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1613269322">1968</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhang,Li</author><author>Wu,Xuewen</author><author>Lin,Xi</author></authors></contributors><auth-address>DepartmentofOtorhinolaryngology,UnionHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan,430022,China;DepartmentofOtolaryngology,EmoryUniversitySchoolofMedicine,615MichaelStreet,Atlanta,GA30322-3030,USA. DepartmentofOtolaryngologyHeadandNeckSurgery,XiangyaHospitalofCentralSouthUniversity,87XiangyaRoad,Changsha,Hunan,410008,China;DepartmentofOtolaryngology,EmoryUniversitySchoolofMedicine,615MichaelStreet,Atlanta,GA30322-3030,USA. DepartmentofOtolaryngology,EmoryUniversitySchoolofMedicine,615MichaelStreet,Atlanta,GA30322-3030,USA.Electronicaddress:xlin2@.</auth-address><titles><title>Genetherapyforgeneticmutationsaffectingnon-sensorycellsinthecochlea</title><secondary-title>Hearingresearch</secondary-title><alt-title>HearRes</alt-title></titles><periodical><full-title>HearingResearch</full-title></periodical><alt-periodical><full-title>HearRes</full-title></alt-periodical><pages>107858</pages><volume>394</volume><dates><year>2020</year></dates><isbn>1878-5891</isbn><accession-num>31791650</accession-num><urls><related-urls><url>/31791650</url></related-urls></urls><electronic-resource-num>10.1016/j.heares.2019.107858</electronic-resource-num><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Zhang,2020#1968"Zhangetal.,2020)，也出现了染色体结构变异诱发小鼠耳聋表型的报道ADDINEN.CITE<EndNote><Cite><Author>Gagnier</Author><Year>2019</Year><RecNum>2053</RecNum><DisplayText>(Gagnieretal.,2019)</DisplayText><record><rec-number>2053</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1614741915">2053</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Gagnier,Liane</author><author>Belancio,VictoriaP.</author><author>Mager,DixieL.</author></authors></contributors><auth-address>1TerryFoxLaboratory,BCCancerandDepartmentofMedicalGenetics,UniversityofBritishColumbia,V5Z1L3,Vancouver,BCCanada. 2DepartmentofStructuralandCellularBiology,TulaneUniversitySchoolofMedicine,TulaneCancerCenter,TulaneCenterforAging,NewOrleans,LA70112USA.</auth-address><titles><title>Mousegermlinemutationsduetoretrotransposoninsertions</title><secondary-title>MobileDNA</secondary-title><alt-title>MobDNA</alt-title></titles><periodical><full-title>MobileDNA</full-title></periodical><alt-periodical><full-title>MobDNA</full-title></alt-periodical><pages>15</pages><volume>10</volume><dates><year>2019</year></dates><isbn>1759-8753</isbn><accession-num>31011371</accession-num><urls><related-urls><url>/31011371</url></related-urls></urls><electronic-resource-num>10.1186/s13100-019-0157-4</electronic-resource-num><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Gagnier,2019#2053"Gagnieretal.,2019)。1.1染色体结构变异分类及研究方法染色体结构变异指基因组上较大片段（大于50bp）的重排，包括片段的插入、缺失、重复、倒位、易位以及拷贝数变化等不同类型ADDINEN.CITE<EndNote><Cite><Author>Alkan</Author><Year>2011</Year><RecNum>1891</RecNum><DisplayText>(Alkanetal.,2011)</DisplayText><record><rec-number>1891</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612174095">1891</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Alkan,C.</author><author>Coe,B.P.</author><author>Eichler,E.E.</author></authors></contributors><auth-address>DepartmentofGenomeSciences,UniversityofWashingtonSchoolofMedicine,FoegeS413C,372015thAveNE,Seattle,Washington,USA.</auth-address><titles><title>Genomestructuralvariationdiscoveryandgenotyping</title><secondary-title>NatRevGenet</secondary-title></titles><periodical><full-title>NatRevGenet</full-title></periodical><pages>363-76</pages><volume>12</volume><number>5</number><edition>2011/03/02</edition><keywords><keyword>DNACopyNumberVariations</keyword><keyword>*GeneticVariation</keyword><keyword>*Genome,Human</keyword><keyword>*Genotype</keyword><keyword>High-ThroughputNucleotideSequencing/economics/methods</keyword><keyword>Humans</keyword><keyword>OligonucleotideArraySequenceAnalysis/economics/methods</keyword><keyword>Polymorphism,SingleNucleotide</keyword><keyword>SequenceAnalysis,DNA/economics/*methods</keyword></keywords><dates><year>2011</year><pub-dates><date>May</date></pub-dates></dates><isbn>1471-0064(Electronic) 1471-0056(Linking)</isbn><accession-num>21358748</accession-num><urls><related-urls><url>/pubmed/21358748</url></related-urls></urls><custom2>PMC4108431</custom2><electronic-resource-num>10.1038/nrg2958</electronic-resource-num></record></Cite></EndNote>(\o"Alkan,2011#1891"Alkanetal.,2011)。近年来，科研人员报道了越来越多染色体结构变异导致的疾病ADDINEN.CITE<EndNote><Cite><Author>Alkan</Author><Year>2011</Year><RecNum>1891</RecNum><DisplayText>(Alkanetal.,2011)</DisplayText><record><rec-number>1891</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612174095">1891</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Alkan,C.</author><author>Coe,B.P.</author><author>Eichler,E.E.</author></authors></contributors><auth-address>DepartmentofGenomeSciences,UniversityofWashingtonSchoolofMedicine,FoegeS413C,372015thAveNE,Seattle,Washington,USA.</auth-address><titles><title>Genomestructuralvariationdiscoveryandgenotyping</title><secondary-title>NatRevGenet</secondary-title></titles><periodical><full-title>NatRevGenet</full-title></periodical><pages>363-76</pages><volume>12</volume><number>5</number><edition>2011/03/02</edition><keywords><keyword>DNACopyNumberVariations</keyword><keyword>*GeneticVariation</keyword><keyword>*Genome,Human</keyword><keyword>*Genotype</keyword><keyword>High-ThroughputNucleotideSequencing/economics/methods</keyword><keyword>Humans</keyword><keyword>OligonucleotideArraySequenceAnalysis/economics/methods</keyword><keyword>Polymorphism,SingleNucleotide</keyword><keyword>SequenceAnalysis,DNA/economics/*methods</keyword></keywords><dates><year>2011</year><pub-dates><date>May</date></pub-dates></dates><isbn>1471-0064(Electronic) 1471-0056(Linking)</isbn><accession-num>21358748</accession-num><urls><related-urls><url>/pubmed/21358748</url></related-urls></urls><custom2>PMC4108431</custom2><electronic-resource-num>10.1038/nrg2958</electronic-resource-num></record></Cite></EndNote>(\o"Alkan,2011#1891"Alkanetal.,2011)。利用全基因组二代测序技术，研究者发现染色体结构变异不仅与常见的人类疾病（如癌症、自闭症、精神分裂症等）相关，也与人类正常表型的多样性相关ADDINEN.CITE<EndNote><Cite><Author>Weischenfeldt</Author><Year>2013</Year><RecNum>1892</RecNum><DisplayText>(Weischenfeldtetal.,2013)</DisplayText><record><rec-number>1892</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612176502">1892</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Weischenfeldt,J.</author><author>Symmons,O.</author><author>Spitz,F.</author><author>Korbel,J.O.</author></authors></contributors><auth-address>GenomeBiologyUnit,EuropeanMolecularBiologyLaboratory,Meyerhofstrasse1,Heidelberg,69117,Germany.</auth-address><titles><title>Phenotypicimpactofgenomicstructuralvariation:insightsfromandforhumandisease</title><secondary-title>NatRevGenet</secondary-title></titles><periodical><full-title>NatRevGenet</full-title></periodical><pages>125-38</pages><volume>14</volume><number>2</number><edition>2013/01/19</edition><keywords><keyword>Animals</keyword><keyword>ComputationalBiology</keyword><keyword>Disease/*genetics</keyword><keyword>DiseaseModels,Animal</keyword><keyword>Epistasis,Genetic</keyword><keyword>GeneDosage</keyword><keyword>GeneRegulatoryNetworks</keyword><keyword>*GeneticAssociationStudies</keyword><keyword>GeneticDiseases,Inborn/genetics</keyword><keyword>*GenomicStructuralVariation</keyword><keyword>Humans</keyword><keyword>Mice</keyword><keyword>Models,Genetic</keyword><keyword>RNA,Messenger/genetics/metabolism</keyword></keywords><dates><year>2013</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1471-0064(Electronic) 1471-0056(Linking)</isbn><accession-num>23329113</accession-num><urls><related-urls><url>/pubmed/23329113</url></related-urls></urls><electronic-resource-num>10.1038/nrg3373</electronic-resource-num></record></Cite></EndNote>(\o"Weischenfeldt,2013#1892"Weischenfeldtetal.,2013)。但是由于二代测序每条读段平均长度为200bp，因此针对大于200bp甚至超过1kb的染色体结构变异检出率会大大降低ADDINEN.CITE<EndNote><Cite><Author>Guan</Author><Year>2016</Year><RecNum>1890</RecNum><DisplayText>(GuanandSung,2016)</DisplayText><record><rec-number>1890</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612172405">1890</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Guan,P.</author><author>Sung,W.K.</author></authors></contributors><auth-address>SchoolofComputing,NationalUniversityofSingapore,117543,Singapore. SchoolofComputing,NationalUniversityofSingapore,117543,Singapore;Computational&MathematicalBiologyGroup,GenomeInstituteofSingapore,138672,Singapore.Electronicaddress:ksung@.sg.</auth-address><titles><title>Structuralvariationdetectionusingnext-generationsequencingdata:Acomparativetechnicalreview</title><secondary-title>Methods</secondary-title></titles><periodical><full-title>Methods</full-title></periodical><pages>36-49</pages><volume>102</volume><edition>2016/02/05</edition><keywords><keyword>DataCuration</keyword><keyword>*GenomicStructuralVariation</keyword><keyword>Genomics/*methods</keyword><keyword>Humans</keyword><keyword>SequenceAnalysis/*methods</keyword><keyword>Software</keyword><keyword>*Next-generationsequencing</keyword><keyword>*Structuralvariation</keyword></keywords><dates><year>2016</year><pub-dates><date>Jun1</date></pub-dates></dates><isbn>1095-9130(Electronic) 1046-2023(Linking)</isbn><accession-num>26845461</accession-num><urls><related-urls><url>/pubmed/26845461</url></related-urls></urls><electronic-resource-num>10.1016/j.ymeth.2016.01.020</electronic-resource-num></record></Cite></EndNote>(\o"Guan,2016#1890"GuanandSung,2016)。逐渐发展成熟的全基因三代测序技术弥补了二代测序的这一短板，可以实现长读长测序，能够检测到基因组中大片段的结构变异（REF_Ref65957537\h图1.14）ADDINEN.CITE<EndNote><Cite><Author>Alkan</Author><Year>2011</Year><RecNum>1891</RecNum><DisplayText>(Alkanetal.,2011)</DisplayText><record><rec-number>1891</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612174095">1891</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Alkan,C.</author><author>Coe,B.P.</author><author>Eichler,E.E.</author></authors></contributors><auth-address>DepartmentofGenomeSciences,UniversityofWashingtonSchoolofMedicine,FoegeS413C,372015thAveNE,Seattle,Washington,USA.</auth-address><titles><title>Genomestructuralvariationdiscoveryandgenotyping</title><secondary-title>NatRevGenet</secondary-title></titles><periodical><full-title>NatRevGenet</full-title></periodical><pages>363-76</pages><volume>12</volume><number>5</number><edition>2011/03/02</edition><keywords><keyword>DNACopyNumberVariations</keyword><keyword>*GeneticVariation</keyword><keyword>*Genome,Human</keyword><keyword>*Genotype</keyword><keyword>High-ThroughputNucleotideSequencing/economics/methods</keyword><keyword>Humans</keyword><keyword>OligonucleotideArraySequenceAnalysis/economics/methods</keyword><keyword>Polymorphism,SingleNucleotide</keyword><keyword>SequenceAnalysis,DNA/economics/*methods</keyword></keywords><dates><year>2011</year><pub-dates><date>May</date></pub-dates></dates><isbn>1471-0064(Electronic) 1471-0056(Linking)</isbn><accession-num>21358748</accession-num><urls><related-urls><url>/pubmed/21358748</url></related-urls></urls><custom2>PMC4108431</custom2><electronic-resource-num>10.1038/nrg2958</electronic-resource-num></record></Cite></EndNote>(\o"Alkan,2011#1891"Alkanetal.,2011)。2015年，TakeshiMizuguchi等人，通过PacBio平台提供的SMRT三代测序技术，发现位于SAMD12基因内含子区域大约4.6kb的插入突变，该结构变异最终被证明为一个患有良性成年家族性肌阵挛癫痫家系的致病变异ADDINEN.CITEADDINEN.CITE.DATA(\o"Mizuguchi,2019#1792"Mizuguchietal.,2019)。图1.SEQ图1.\*ARABIC1染色体结构变异的分类经典染色体结构变异检测结果示意图。图中展示的染色体结构变异类型包括缺失（Deletion）、新序列插入（Novelsequenceinsertion）、转座子插入（Mobile-elementinsertion）、串联重复（Tandemduplication）、间隔重复（Interspersedduplication）、倒位（Inversion）及易位（Translocation）。其中，上方带箭头的横线代表参考基因组（Ref.），相应染色体变异的检测结果在参考基因组下方展示。ADDINEN.CITE<EndNote><Cite><Author>Alkan</Author><Year>2011</Year><RecNum>1891</RecNum><DisplayText>(Alkanetal.,2011)</DisplayText><record><rec-number>1891</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612174095">1891</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Alkan,C.</author><author>Coe,B.P.</author><author>Eichler,E.E.</author></authors></contributors><auth-address>DepartmentofGenomeSciences,UniversityofWashingtonSchoolofMedicine,FoegeS413C,372015thAveNE,Seattle,Washington,USA.</auth-address><titles><title>Genomestructuralvariationdiscoveryandgenotyping</title><secondary-title>NatRevGenet</secondary-title></titles><periodical><full-title>NatRevGenet</full-title></periodical><pages>363-76</pages><volume>12</volume><number>5</number><edition>2011/03/02</edition><keywords><keyword>DNACopyNumberVariations</keyword><keyword>*GeneticVariation</keyword><keyword>*Genome,Human</keyword><keyword>*Genotype</keyword><keyword>High-ThroughputNucleotideSequencing/economics/methods</keyword><keyword>Humans</keyword><keyword>OligonucleotideArraySequenceAnalysis/economics/methods</keyword><keyword>Polymorphism,SingleNucleotide</keyword><keyword>SequenceAnalysis,DNA/economics/*methods</keyword></keywords><dates><year>2011</year><pub-dates><date>May</date></pub-dates></dates><isbn>1471-0064(Electronic) 1471-0056(Linking)</isbn><accession-num>21358748</accession-num><urls><related-urls><url>/pubmed/21358748</url></related-urls></urls><custom2>PMC4108431</custom2><electronic-resource-num>10.1038/nrg2958</electronic-resource-num></record></Cite></EndNote>(\o"Alkan,2011#1891"Alkanetal.,2011)。1.2转座子的发现及特点文献报道指出，人类基因组中包含大量结构变异，这些结构变异涉及到的核苷酸总数甚至超过所有SNP相关的核苷酸ADDINEN.CITE<EndNote><Cite><Author>Guan</Author><Year>2016</Year><RecNum>1890</RecNum><DisplayText>(GuanandSung,2016)</DisplayText><record><rec-number>1890</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612172405">1890</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Guan,P.</author><author>Sung,W.K.</author></authors></contributors><auth-address>SchoolofComputing,NationalUniversityofSingapore,117543,Singapore. SchoolofComputing,NationalUniversityofSingapore,117543,Singapore;Computational&MathematicalBiologyGroup,GenomeInstituteofSingapore,138672,Singapore.Electronicaddress:ksung@.sg.</auth-address><titles><title>Structuralvariationdetectionusingnext-generationsequencingdata:Acomparativetechnicalreview</title><secondary-title>Methods</secondary-title></titles><periodical><full-title>Methods</full-title></periodical><pages>36-49</pages><volume>102</volume><edition>2016/02/05</edition><keywords><keyword>DataCuration</keyword><keyword>*GenomicStructuralVariation</keyword><keyword>Genomics/*methods</keyword><keyword>Humans</keyword><keyword>SequenceAnalysis/*methods</keyword><keyword>Software</keyword><keyword>*Next-generationsequencing</keyword><keyword>*Structuralvariation</keyword></keywords><dates><year>2016</year><pub-dates><date>Jun1</date></pub-dates></dates><isbn>1095-9130(Electronic) 1046-2023(Linking)</isbn><accession-num>26845461</accession-num><urls><related-urls><url>/pubmed/26845461</url></related-urls></urls><electronic-resource-num>10.1016/j.ymeth.2016.01.020</electronic-resource-num></record></Cite></EndNote>(\o"Guan,2016#1890"GuanandSung,2016)。前期结构变异的相关研究主要关注基因的拷贝数变异ADDINEN.CITE<EndNote><Cite><Author>Scherer</Author><Year>2007</Year><RecNum>2055</RecNum><DisplayText>(Schereretal.,2007)</DisplayText><record><rec-number>2055</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1614743289">2055</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Scherer,StephenW.</author><author>Lee,Charles</author><author>Birney,Ewan</author><author>Altshuler,DavidM.</author><author>Eichler,EvanE.</author><author>Carter,NigelP.</author><author>Hurles,MatthewE.</author><author>Feuk,Lars</author></authors></contributors><auth-address>TheCentreforAppliedGenomicsandPrograminGeneticsandGenomicBiology,TheHospitalforSickChildren,101CollegeStreet,Room14-701,OntarioM5G1L7,Canada.steve@genet.sickkids.on.ca</auth-address><titles><title>Challengesandstandardsinintegratingsurveysofstructuralvariation</title><secondary-title>Naturegenetics</secondary-title><alt-title>NatGenet</alt-title></titles><periodical><full-title>NatureGenetics</full-title></periodical><alt-periodical><full-title>NatGenet</full-title></alt-periodical><pages>S7-15</pages><volume>39</volume><number>7Suppl</number><dates><year>2007</year></dates><isbn>1061-4036</isbn><accession-num>17597783</accession-num><urls><related-urls><url>/17597783</url></related-urls></urls><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Scherer,2007#2055"Schereretal.,2007)，而较少探究高拷贝的串联或间隔重复序列以及插入序列等变异类型。后者通常是转座子通过复制-粘贴的转座机制实现的，比如转座子L1插入产生的结构变异ADDINEN.CITEADDINEN.CITE.DATA(\o"Gresham,2008#1901"Greshametal.,2008;\o"Huang,2010#1696"Huangetal.,2010)。转座子是基因组中一段能够发生位置变化的序列ADDINEN.CITE<EndNote><Cite><Author>Kerachian</Author><Year>2019</Year><RecNum>1902</RecNum><DisplayText>(KerachianandKerachian,2019)</DisplayText><record><rec-number>1902</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1612318667">1902</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kerachian,M.A.</author><author>Kerachian,M.</author></authors></contributors><auth-address>MedicalGeneticsResearchCenter,MashhadUniversityofMedicalSciences,Mashhad,Iran.;DepartmentofMedicalGenetics,FacultyofMedicine,MashhadUniversityofMedicalSciences,Mashhad,Iran;CancerGeneticsResearchUnit,RezaRadiotherapyandOncologyCenter,Mashhad,Iran.Electronicaddress:amin.kerachian@mail.mcgill.ca. FacultyofMedicine,McGillUniversity,Montreal,Canada;ResearchInstituteatMcGillUniversityHealthCenter,Montreal,Canada.</auth-address><titles><title>Longinterspersednucleotideelement-1(LINE-1)methylationincolorectalcancer</title><secondary-title>ClinChimActa</secondary-title></titles><periodical><full-title>ClinChimActa</full-title></periodical><pages>209-214</pages><volume>488</volume><edition>2018/11/18</edition><keywords><keyword>Biomarkers,Tumor/*genetics</keyword><keyword>ColorectalNeoplasms/diagnosis/*genetics</keyword><keyword>Humans</keyword><keyword>LongInterspersedNucleotideElements/*genetics</keyword><keyword>Methylation</keyword><keyword>Cancer</keyword><keyword>Colon</keyword><keyword>Line</keyword><keyword>Longinterspersednucleotideelement-1</keyword><keyword>Sine</keyword><keyword>Sva</keyword></keywords><dates><year>2019</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1873-3492(Electronic) 0009-8981(Linking)</isbn><accession-num>30445031</accession-num><urls><related-urls><url>/pubmed/30445031</url></related-urls></urls><electronic-resource-num>10.1016/j.cca.2018.11.018</electronic-resource-num></record></Cite></EndNote>(\o"Kerachian,2019#1902"KerachianandKerachian,2019)。1940到1950年间，Barbara在深入研究玉米胚乳颜色形成的遗传机制过程中发现了转座子ADDINEN.CITE<EndNote><Cite><Author>McClintock</Author><Year>1950</Year><RecNum>2057</RecNum><DisplayText>(McClintock,1950)</DisplayText><record><rec-number>2057</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1614743890">2057</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>McClintock,B.</author></authors></contributors><titles><title>Theoriginandbehaviorofmutablelociinmaize</title><secondary-title>ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica</secondary-title><alt-title>ProcNatlAcadSciUSA</alt-title></titles><periodical><full-title>ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica</full-title></periodical><alt-periodical><full-title>ProcNatlAcadSciUSA</full-title></alt-periodical><pages>344-355</pages><volume>36</volume><number>6</number><dates><year>1950</year></dates><isbn>0027-8424</isbn><accession-num>15430309</accession-num><urls><related-urls><url>/15430309</url></related-urls></urls><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"McClintock,1950#2057"McClintock,1950)。1988年，Kazazian等人首次在A型血友病患者FVIII基因的外显子14中发现L1元件的插入，表明L1转座子的插入突变可能导致疾病的发生ADDINEN.CITE<EndNote><Cite><Author>Kazazian</Author><Year>1988</Year><RecNum>2062</RecNum><DisplayText>(Kazazianetal.,1988)</DisplayText><record><rec-number>2062</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1614744308">2062</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kazazian,H.H.</author><author>Wong,C.</author><author>Youssoufian,H.</author><author>Scott,A.F.</author><author>Phillips,D.G.</author><author>Antonarakis,S.E.</author></authors></contributors><auth-address>DepartmentofPediatrics,JohnsHopkinsUniversitySchoolofMedicine,Baltimore,Maryland21205.</auth-address><titles><title>HaemophiliaAresultingfromdenovoinsertionofL1sequencesrepresentsanovelmechanismformutationinman</title><secondary-title>Nature</secondary-title><alt-title>Nature</alt-title></titles><periodical><full-title>Nature</full-title></periodical><alt-periodical><full-title>Nature</full-title></alt-periodical><pages>164-166</pages><volume>332</volume><number>6160</number><dates><year>1988</year></dates><isbn>0028-0836</isbn><accession-num>2831458</accession-num><urls><related-urls><url>/2831458</url></related-urls></urls><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Kazazian,1988#2062"Kazazianetal.,1988)。根据不同的转座机制，可以将转座子分为两大类，I型转座子通过复制-粘贴的方式进行转座，因此也被称为逆转录转座子或逆转座子；II型转座子则直接通过剪切-粘贴的方式进行转座，因此也被称为DNA转座子。逆转座子通常又可分为三类：具有长末端重复序列（longterminalrepeat，LTR）的逆转座子，LTR转座子类似于逆转录病毒，其自身含有编码反转录酶的序列，也被称为内源性逆转录病毒转座子ADDINEN.CITEADDINEN.CITE.DATA(\o"Grandi,2018#1955"GrandiandTramontano,2018)；长散在核元件（longinterspersednuclearelement，LINE），能够被RNA聚合酶II转录，同时包含编码逆转录酶的序列，因此能够自主转座；短散在核元件（shortinterspersednuclearelements，SINE）能够被RNA聚合酶III转录，与LINE相比不包含编码逆转录酶的序列，因此需要依赖LINE等自主转座子进行转座，通常被称为非自主转座子ADDINEN.CITE<EndNote><Cite><Author>Kapitonov</Author><Year>2008</Year><RecNum>2135</RecNum><DisplayText>(KapitonovandJurka,2008)</DisplayText><record><rec-number>2135</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1616221012">2135</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kapitonov,VladimirV.</author><author>Jurka,Jerzy</author></authors></contributors><titles><title>AuniversalclassificationofeukaryotictransposableelementsimplementedinRepbase</title><secondary-title><styleface="normal"font="default"size="100%">Nature</style><styleface="normal"font="default"charset="134"size="100%"></style><styleface="normal"font="default"size="100%">ReviewGenetics</style></secondary-title><alt-title>NatRevGenet</alt-title></titles><periodical><full-title>NatureReviewGenetics</full-title></periodical><alt-periodical><full-title>NatRevGenet</full-title></alt-periodical><volume>9</volume><number>5</number><dates><year>2008</year></dates><isbn>1471-0064</isbn><accession-num>18421312</accession-num><urls><related-urls><url>/18421312</url></related-urls></urls><electronic-resource-num>10.1038/nrg2165-c1</electronic-resource-num><remote-database-name>PubMed</remote-database-name><language>eng</language></record></Cite></EndNote>(\o"Kapitonov,2008#2135"KapitonovandJurka,2008)1.3人类和小鼠基因组中的转座子经过漫长的进化，大约45%的人类基因组序列为转座子，包含DNA转座子、LTR转座子和以L1为代表的自主转座子等类型，其中大多数转座子元件已经失活，但L1转座子依旧保留转座活性，促进了人类基因组的多样性ADDINEN.CITEADDINEN.CITE.DATA(\o"Lander,2001#2128"Landeretal.,2001)。经典的L1转座子通常包括6,000-7,000碱基对（basepair，bp），含有编码两个蛋白ORF1和ORF2的开放阅读框（openreadingframe,ORF），在编码蛋白序列的外侧分别为5’和3’非翻译区（untranslatedregions，UTRs），及紧邻的靶位点重复序列（targetsiteduplications，TSDs）（REF_Ref65958815\h图1.15）。人类和小鼠的L1转座子元件结构类似，5’UTR区域均包含RNA聚合酶转录需要的启动子；ORF1编码逆转录所需的蛋白ORF1p，其包含CC结构域（coiled-coildomain）、RNA识别序列（RNArecognitionmotif，RRM）以及C端结构域；ORF2编码具有核酸内切酶活性和逆转录酶活性的ORFp2蛋白，为L1元件逆转录转座过程中整合到基因组靶向位点不可或缺的部分（REF_Ref65958815\h图1.15）ADDINEN.CITE<EndNote><Cite><Author>Kazazian</Author><Year>2017</Year><RecNum>361</RecNum><DisplayText>(KazazianandMoran,2017)</DisplayText><record><rec-number>361</rec-number><foreign-keys><keyapp="EN"db-id="0sfs5dvpdfxs2ketx0jvdwt2xdeaafrx2saw"timestamp="1584866606">361</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kazazian,H.H.,Jr.</author><author>Moran,J.V.</author></authors></contributors><auth-address>FromtheMcKusick-NathansInstituteofGeneticMedicine,JohnsHopkinsSchoolofMedicine,Baltimore(H.H.K.),andtheDepartmentsofHumanGeneticsandInternalMedicine,UniversityofMichiganMedicalSchoo