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基于基因测序分型技术建立NXB重组近交系小鼠群体模型

Establishment of NXB Recombinant Inbred Mouse Population Model Based on Genotyping by Sequencing Technique
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摘要 为构建NOD/ShiLtJ-C57BL/6J重组近交系(recombinant inbred,RI)(简称为NXB RI)小鼠(Mus musculus)群体模型,以保证亲本基因型覆盖度的均衡及提高其近交效率,本研究采用基因测序分型(genotyping by sequencing,GBS)技术对200只F5代NXB RI小鼠群体进行基因分型测序,然后通过主成分分析、群体间遗传分化系数与遗传距离分析、个体间亲缘关系分析等鉴定小鼠群体亲本基因型覆盖度以及近交程度。测序覆盖F5代NXB RI小鼠36个亚群的200个样本,共测得115634个单核苷酸多态性(single nucleotide polymorphism,SNP)位点,其中41.67%为C57BL/6J纯合位点,27.05%为NOD/ShiLtJ纯合位点,26.79%为杂合位点,SNP位点在所有染色体中均有分布;94.6%的亚群F_(st)值大于0.15,表明大部分的F5代NXB RI小鼠群体之间的遗传结构差异大,分化程度较高;200个NXB RI样本间的状态一致性(identity by state,IBS)距离平均值为0.667,最高为0.925,最低为0.480,可为下一代繁殖筛选提供依据。另外,对F5代200只NXB RI小鼠进行听力和空腹血糖测试,结果表明两种表型的数据均符合正态分布。以上研究结果表明,F5代NXB RI小鼠的亲本基因型覆盖度分布较为均衡,能够保留较多的NXB RI品系,所产生的NXB RI群体可作为一代全新的遗传参考群体,可作为相关复杂遗传性疾病研究模型。 In order to build a mouse(Mus musculus)population model of NOD/ShiLtJ-C57BL/6J recombinant inbred(RI)strain(NXB RI for short),to ensure the balance of parental gene coverage and to improve inbreeding efficiency,this study used genotyping by sequencing(GBS)technology to genotype and sequence 200 F5 NXB RI strains,and then principal component analysis,genetic differen-tiation coefficient and genetic distance analysis and kinship analysis among individuals were used to identify the genotype coverage and inbreeding degree of mouse population parents.By sequencing 200 samples from 36 subgroups of F5 NXB RI strains,a total of 115634 single nucleotide polymorphism(SNP)were measured,of which 41.67%were C57BL/6J homozygous sites,27.05%were NOD/ShiLtJ homozygous sites,26.79%were heterozygous sites,and the SNP sites were distributed in all chromosomes;94.6%of the subgroups had F_(st) values greater than 0.15,indicating that the genetic structure of most F5 NXB RI strains differed greatly and the degree of differentiation was high.The mean value of identity by state(IBS)distance among the 200 NXB RI samples was 0.667,the highest was 0.925,and the lowest was 0.480,which could provide basis for next generation breeding screening.The data of hearing phenotype and fasting blood glucose phenotype of F5 NXB RI strains followed normal distribution.The results of the above studies showed that F5 NXB RI strains had a relatively balanced distribution of parental genotype coverage,and could retain more NXB RI strains.The resulting NXB RI strains,as a new generation of genetic reference population,can be used as a research model for related complex genetic diseases.
作者 王芹 奎丽红 李慧 吴杰 崔庆轩 徐福意 郑体花 郑庆印 WANG Qin;KUI Lihong;LI Hui;WU Jie;CUI Qingxuan;XU Fuyi;ZHENG Tihua;ZHENG Qingyin(School of Special Education,Binzhou Medical University,Yantai,264003)
出处 《基因组学与应用生物学》 CAS CSCD 北大核心 2023年第2期183-193,共11页 Genomics and Applied Biology
基金 国家自然科学基金项目(81530030,81500797)资助
关键词 基因测序分型技术 NOD/ShiLtJ-C57BL/6J重组近交系 动物模型 亲缘关系 Genotyping by sequencing technology NOD/ShiLtJ-C57BL/6J recombinant inbred Animal model Kinship
作者简介 通信作者:郑庆印,2363616842@qq.com
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