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高质量的小鼠参考基因组揭示了小鼠蛋白质编码景观的结构复杂性

Mohab Helmy¹, Jin U Li², Xinyu F Yan²

¹European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SD, UK; Department of Biochemistry, Department of Genetics and Gurdon Institute, University of Cambridge, Cambridge, UK.

|December 2, 2025

概括

我们展示了17个高质量的小鼠基因组,改善了基因注释和解决复杂区域. 这个资源增强了RNA测序分析,揭示了小鼠菌株的遗传变异.

科学领域:

基因组学就是基因组学.
进行比较的基因组学.
分子生物学分子生物学

背景情况:

高质量的参考基因组对于准确的遗传分析至关重要.
以前的小鼠基因组组合 (例如,GRCm39) 有不完整或未解决的区域.
了解不同老鼠菌株的遗传变异对于研究至关重要.

研究的目的:

为了生成17个高质量,长期阅读的同系鼠株基因组的综合集合,并提供完整的注释.
解决以前没有注释或不完整的基因组区域,包括MHC,防御蛋白,T细胞受体和Ly49复合体.
识别和定位非参考基因,并在小鼠菌株中表征可变数串联重复 (VNTRs).

主要方法:

对于17个内生小鼠菌株的长读测序数据的生成.
De novo基因组组装和注释,专注于解决复杂的基因组区域.
在编码区域内,全基因组扫描可变数串联重复 (VNTRs).
对新的基因组注释与GRCm39参考进行比较分析.

主要成果:

一个由17个高质量的小鼠基因组组成的集合,其结合性N50s范围从0.8-33.9 Mbp.
以前不完整的基因组区域的分辨率,包括MHC,防御蛋白,T细胞受体和Ly49复合体.
定位了数百个非参考基因,并识别了400多个具有编码VNTR多态的基因.
在RNA测序 (RNA-seq) 分析中得到了明显的改善,读取映射和识别表达差异在2.1%的编码PWK/PhJ基因中的差异增加了5.1%.

结论:

展示的高质量的小鼠基因组为遗传学和基因组学研究提供了显著改进的参考.
复杂区域的增强注释和分辨率有助于发现和描述新型基因和遗传变异.
这些新的参考基因组大大改善了RNA测序分析,使得能够更准确地检测小鼠菌株间的基因表达差异和遗传多态性.

关键词:

基因组变化的基因组变化.实验室老鼠实验室老鼠小鼠基因组的基因组.潘格诺姆 (pangenome) 是一个名字.测序的测序是指测序的测序.

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