High-Resolution Genetic Mapping Using the Mouse Diversity Outbred Population
High-Resolution Genetic Mapping Using the Mouse Diversity Outbred Population
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DOI：
10.1534/genetics.111.132597
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发表时间：
2012-02-01
期刊：
影响因子：
3.3
通讯作者：
Churchill, Gary A.
中科院分区：
文献类型：
--
作者：
Svenson, Karen L.;Gatti, Daniel M.;Churchill, Gary A.
JAX Diversity Outbred 群体是一种新的小鼠资源，源自部分近交的协作杂交品系，并通过随机异交维持。因此，它分离出与协作杂交相同的等位基因变体，但将这些变体嵌入独特的群体结构中，其中每只动物都具有高度的杂合性并携带独特的等位基因组合。表型多样性是惊人的，并且通常与协作杂交的创始菌株中看到的表型不同。早期几代多样性远交小鼠的等位基因频率和重组密度与基于交配设计模拟的预期一致。我们描述了使用该资源进行遗传图谱分析的方法，并通过将血清胆固醇性状图谱到仅包含 11 个基因的 3 号染色体上的 2 Mb 区域，展示了该群体所实现的功效和高图谱分辨率。对估计的等位基因效应与创始菌株的完整基因组序列数据相结合的分析将候选多态性库减少到七个 SNP，其中五个位于 Foxo1 基因上游的基因间区域。
The JAX Diversity Outbred population is a new mouse resource derived from partially inbred Collaborative Cross strains and maintained by randomized outcrossing. As such, it segregates the same allelic variants as the Collaborative Cross but embeds these in a distinct population architecture in which each animal has a high degree of heterozygosity and carries a unique combination of alleles. Phenotypic diversity is striking and often divergent from phenotypes seen in the founder strains of the Collaborative Cross. Allele frequencies and recombination density in early generations of Diversity Outbred mice are consistent with expectations based on simulations of the mating design. We describe analytical methods for genetic mapping using this resource and demonstrate the power and high mapping resolution achieved with this population by mapping a serum cholesterol trait to a 2-Mb region on chromosome 3 containing only 11 genes. Analysis of the estimated allele effects in conjunction with complete genome sequence data of the founder strains reduced the pool of candidate polymorphisms to seven SNPs, five of which are located in an intergenic region upstream of the Foxo1 gene.