先天性晚发白内障FVB小鼠突变基因定位及筛选
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东华大学化学化工与生物工程学院,上海 201600

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R-33

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The localization and screening of mutant gene in late-onset congenital cataract FVB mouse
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College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201600, China

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    摘要:

    目的 以自发突变导致的先天性晚发白内障小鼠为模型,进行遗传方式鉴定和白内障相关基因定位分析。 方法 首先通过显微镜观察组织切片鉴定白内障病理状态,其次通过构建家系确定先天性晚发白内障在FVB小鼠中的遗传方式,其次利用多重PCR靶向测序进行 100只F2代小鼠的全基因组SNP扫描定位,最后利用全外显子测序筛选出候选突变基因。 结果 组织切片表明自发突变引起为典型白内障性状,全基因组扫描定位显示11号染色体上的 rs4228772 SNP位点与白内障表型连锁程度最高;全外显子测序结果进一步表明11号染色体 上有三个基因产生了自发突变,分别是Sfi1,ObscnPtrh2结论 本研究使用全基因组 SNP 扫描连锁分析与外显子测序相结合的策略,可在已知参考基因组的物种中快速定位基因突变,结果确定了11号染色体上的三个突变基因为先天性晚发型白内障的候选基因,并以显性方式遗传。 该策略亦可应用于其它遗传背景清晰的模式哺乳动物的基因功能研究。

    Abstract:

    Objective To identify the genetic pattern and locate the genes related to late-onset congenital cataract FVB mouse. Methods First, the phenotype of cataract mice was identified using histopathological slides and the genetic pattern of congenital cataract phenotype was identified by constructing pedigrees. Second, the linked chromosome was located by whole-genome SNP scanning based on multiplex PCR targeted sequencing. Finally, screening of candidate mutant genes was performed by sequencing the whole exome of two cataract mice, one wild-type mouse, and four F2 cataract mice with a mixed genome. Results The result of whole-genome scanning of 100 F2 mice showed the highest linkage between rs4228772 SNP on chromosome 11 and the cataract phenotype, with a 82. 11% homozygous rate. The result of whole-exome sequencing further demonstrated three genes that had spontaneously mutated on chromosome 11:Sfi1,Obscn,andPtrh2. Conclusions The combination of whole-genome SNP scanning and whole-exome sequencing strategies revealed that congenital late-onset cataract was caused by mutated genes on chromosome 11 and inherited as a dominant trait. This method may also be applied to the study of gene function in other model mammals with a clear genetic background.

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庞铂实,钱强,徐园,肖君华,周宇荀,李凯.先天性晚发白内障FVB小鼠突变基因定位及筛选[J].中国比较医学杂志,2020,30(1):81~87.

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  • 收稿日期:2019-07-19
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  • 在线发布日期: 2020-08-19
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