遗传多样性小鼠资源及其遗传学特点

Establishment and genetic characteristics of the Genetic Diversity mice resource

目的建立从群体水平体现遗传多样性特点的新型小鼠资源,并初步探讨其遗传学特点。方法(1)多个亲本以重组杂交的方式分别建立携带有多亲本遗传信息的近交系和远交系小鼠;(2)通过全外显子测序,比较分析两个小鼠群体的遗传学特点;(3)通过子代与亲本品系基因组序列的分析,绘制遗传多样性小鼠资源的染色体物理图谱,并统计亲本对子代小鼠的遗传贡献。结果(1)遗传多样性近交系小鼠具有遗传稳定、表型一致的特点,适用于简单快速的表型-基因型相关性分析工作;(2)相比近交系,遗传多样性远交系小鼠拥有更好的繁殖能力,以及更丰富的遗传变异。每个远交系小鼠都是独特的个体,适合更细粒度的微调控遗传学机制研究。这些远交系小鼠的染色体表现出更为马赛克化的特点;(3)原始亲本对子代品系的遗传贡献并非均一等分,存在遗传偏好。结论相比传统单一遗传背景的小鼠,通过多亲本建立的遗传多样性近交系和远交系小鼠资源在系统遗传学的研究中各具优势、互为补充,为复杂性状遗传学机制的研究提供了强有力的工具。

Objective We aimed to establish a novel resource consisting of genetically diverse mice and perform a preliminary characterization of the genetic traits of these mice.Methods(1)A multi-parent panel was used to create the Genetic Diversity mice through appropriate crosses.(2)Whole-exon sequencing was used to analyze the genetic characteristics of the established Genetic Diversity outbred and inbred mice.(3)Using the genome sequences of the founders and offspring,we created the chromosome physical maps of these mice and calculated the founder contributions.Results(1)Genetic Diversity inbred mice were characterized by stable inheritance and consistent phenotype and were suitable for rapid phenotypic correlation analysis.(2)Compared with the inbred mice,the Genetic Diversity outbred mice showed superior growth and reproductive performance,and more genetic variation,which led to a“mosaic-like”chromosomal pattern.As unique individuals,the outbred mice are ideal for the study of subtle genetic regulatory mechanisms.(3)The founder contributions to the progeny lines were not uniform and genetic preference existed among the offspring.Conclusions Compared with the more conventional inbred mice,the Genetic Diversity mice established by breeding from multiple lines possessed diverse genetic variations.The Genetic Diversity outbred and inbred lines are associated with pros and cons but complement one another,and together represent a novel and powerful tool for the study of complex genetic traits.