Collaborative Cross mice and their power to map host susceptibility to Aspergillus fumigatus infection
Collaborative Cross mice and their power to map host susceptibility to Aspergillus fumigatus infection
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DOI：
10.1101/gr.118786.110
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发表时间：
2011-08-01
期刊：
影响因子：
7
通讯作者：
Iraqi, Fuad A.
中科院分区：
文献类型：
--
作者：
Durrant, Caroline;Tayem, Hanna;Iraqi, Fuad A.
协作杂交（CC）是小鼠重组近交系的遗传参考组，旨在解剖复杂的性状和基因网络。每个系独立地源自8个遗传多样性的创始者品系，使得CC系的基因组一旦完全近交，则是创始者单倍型的细粒纯合嵌合体。我们提出了一个分析的120个CC线，从一个队列的CC繁殖在特拉维夫大学与牛津大学合作，在本研究的时间是第6和第12代之间的近亲繁殖和基本上纯合的170，000 SNP。我们展示了CC基因组如何分解成马赛克，我们确定了基因座，携带缺陷或过量的创始人，许多是缺乏野生来源的菌株WSB/EiJ和PWK/PhJ。我们对来自66个CC系的371只小鼠进行了表型分析，以确定对烟曲霉感染的易感性。感染后的存活时间在CC系之间差异显著。数量性状基因座（QTL）定位确定了全基因组显着的QTL在染色体2，3，8，10（两个QTL），15，和18。模拟结果表明，QTL定位分辨率（QTL峰值和真实位置之间的中位距离）在0.47和1.18 Mb之间变化。大多数QTL涉及野生型创始菌株之间的对比，因此不会在经典近交系之间分离。使用CC创始菌株基因组的变异数据进一步完善了这些QTL，并提出了几个候选基因。这些结果支持使用CC解剖复杂的性状。
The Collaborative Cross (CC) is a genetic reference panel of recombinant inbred lines of mice, designed for the dissection of complex traits and gene networks. Each line is independently descended from eight genetically diverse founder strains such that the genomes of the CC lines, once fully inbred, are fine-grained homozygous mosaics of the founder haplotypes. We present an analysis of 120 CC lines, from a cohort of the CC bred at Tel Aviv University in collaboration with the University of Oxford, which at the time of this study were between the sixth and 12th generations of inbreeding and substantially homozygous at 170,000 SNPs. We show how CC genomes decompose into mosaics, and we identify loci that carry a deficiency or excess of a founder, many being deficient for the wild-derived strains WSB/EiJ and PWK/PhJ. We phenotyped 371 mice from 66 CC lines for a susceptibility to Aspergillus fumigatus infection. The survival time after infection varied significantly between CC lines. Quantitative trait locus (QTL) mapping identified genome-wide significant QTLs on chromosomes 2, 3, 8, 10 (two QTLs), 15, and 18. Simulations show that QTL mapping resolution (the median distance between the QTL peak and true location) varied between 0.47 and 1.18 Mb. Most of the QTLs involved contrasts between wild-derived founder strains and therefore would not segregate between classical inbred strains. Use of variation data from the genomes of the CC founder strains refined these QTLs further and suggested several candidate genes. These results support the use of the CC for dissecting complex traits.