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结构变异的小鼠数据库使得自发性小鼠淋巴瘤的遗传结构能够被描述

Wenlong Ren¹, Zhuoqing Fang¹, Egor Dolzhenko²

¹Department of Anesthesia, Pain and Perioperative Medicine, Stanford University School of Medicine, Stanford CA 94305.

bioRxiv : the preprint server for biology

|January 27, 2025

概括

研究人员使用长读序列测序绘制了40种小鼠菌株的遗传变异图,识别了新的结构变异 (SV). 这导致了SJL小鼠B细胞淋巴瘤易感性的新双基因模型,揭示了影响淋巴瘤发展的删除SV.

科学领域:

基因组学就是基因组学.
癌症生物学癌症生物学
免疫学免疫学免疫学

背景情况:

在小鼠模型中表征遗传变异对于理解生物医学特征至关重要.
结构变异 (SV) 是遗传多样性的重要来源,但由于技术挑战,它们在当前的小鼠菌株数据中表现不足.

研究的目的:

为了创建一个全面的结构变异 (SVs) 的地图,跨越40种内生小鼠菌株.
在SJL小鼠中发现有助于B细胞淋巴瘤易感性的新遗传因素.

主要方法:

高质量的长读序列测序在40种同系鼠标菌株上进行.
为最佳识别和验证各种SV类型,开发了一种专门的生物信息管道.
创建了一个SVs,单核酸多态 (SNP) 和插入/删除的综合数据库.

主要成果:

为40个小鼠菌株建立了573,191个SV的数据库,包括10,815个重复和2,115个反转.
发现了一种新的SJL小鼠B细胞淋巴瘤易感性的双基因模型.
该模型涉及已知的内源性逆转录病毒蛋白和新发现的删除SV,该SV会消去促进淋巴瘤的蛋白质.

结论:

生成的SV数据库为小鼠遗传模型研究提供了宝贵的资源.
鉴定到的双基因模型为SJL淋巴瘤的发病过程提供了新的见解.
这项研究可能会揭示类似人体淋巴瘤背后的机制.

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