The Diversity Outbred mouse population.
The Diversity Outbred mouse population.
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DOI：
10.1007/s00335-012-9414-2
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发表时间：
2012-10
期刊：
影响因子：
2.5
通讯作者：
Svenson, Karen L.
中科院分区：
文献类型：
--
作者：
Churchill, Gary A.;Gatti, Daniel M.;Munger, Steven C.;Svenson, Karen L.
多样性远交（DO）群体是源自与协作杂交（CC）近交品系相同的八个创始品系的异质原种。遗传异质性DO小鼠表现出广泛的表型。自然水平的杂合性提供了遗传缓冲，因此，DO小鼠很健壮并且繁殖良好。DO中的遗传图谱分析提出了新的挑战和机遇。需要专门的算法来从高密度SNP阵列数据重建单体型。这8种单倍型可以组合成36种可能的双倍型，这在QTL定位分析中是必须考虑的。这里必须考虑到指定管辖区的人口结构。估计等位基因效应的8个创始人单倍型提供的信息，是不提供在双亲杂交，可以大大减少候选基因座的数量。等位基因效应还可以区分QTL的机会共定位和多效性，这为在表达QTL研究中建立因果关系提供了基础。我们建议QTL定位研究的样本量为200至800只小鼠，大于传统杂交。CC近交系为DO作图结果的独立验证提供了资源。DO的遗传异质性可以为我们将结论推广到其他遗传多样性群体的能力提供强大的优势。遗传多样性也有助于避免识别仅在有限遗传背景下发生的特异质反应的陷阱。与CC、DO及其创始菌株相关的信息学工具和数据资源正在迅速发展。我们预计，随着我们的社区开始采用和利用这些新的遗传资源种群，将出现大量新的结果。
The Diversity Outbred (DO) population is a heterogeneous stock derived from the same eight founder strains as the Collaborative Cross (CC) inbred strains. Genetically heterogeneous DO mice display a broad range of phenotypes. Natural levels of heterozygosity provide genetic buffering and, as a result, DO mice are robust and breed well. Genetic mapping analysis in the DO presents new challenges and opportunities. Specialized algorithms are required to reconstruct haplotypes from high-density SNP array data. The eight founder haplotypes can be combined into 36 possible diplotypes, which must be accommodated in QTL mapping analysis. Population structure of the DO must be taken into account here. Estimated allele effects of 8 founder haplotypes provide information that is not available in two-parent crosses and can dramatically reduce the number of candidate loci. Allele effects can also distinguish chance co-location of QTL from pleiotropy – which provides a basis for establishing causality in expression QTL studies. We recommended sample sizes of 200 to 800 mice for QTL mapping studies, larger than for traditional crosses. The CC inbred strains provide a resource for independent validation of DO mapping results. Genetic heterogeneity of the DO can provide a powerful advantage in our ability to generalize conclusions to other genetically diverse populations. Genetic diversity can also help to avoid the pitfall of identifying an idiosyncratic reaction that occurs only in a limited genetic context. Informatics tools and data resources associated with the CC, the DO, and their founder strains are developing rapidly. We anticipate a flood of new results to follow as our community begins to adopt and utilize these new genetic resource populations.
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