Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis

Genetic structure of the LXS panel of recombinant inbred mouse strains: a powerful resource for complex trait analysis
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DOI:
10.1007/s00335-004-2380-6
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发表时间:
2004-08-01
期刊:
影响因子:
2.5
通讯作者:
Johnson, TE
Johnson, TE
中科院分区:
生物学4区
文献类型:
--
作者:
Williams, RW;Bennett, B;Johnson, TE

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LXS重组自交系(RI)是一个新的和非常大的作图面板,适用于分析具有相对较高的功率的复杂性状。这组由77个品系组成--是其他RI组的两倍多--并且通常将提供足够的统计功效(β = 0.8)来定位数量性状基因座(QTL),这些QTL占遗传方差的25%左右,全基因组p < 0.05。为了表征这组新的RI菌株的遗传结构,我们对分布在所有常染色体和X染色体上的330个MIT微卫星标记进行了基因分型,并组装了错误检查的减数分裂重组图,其平均F-2调整标记间距接近4 cM。LXS组具有与随机分离和随后的等位基因固定一致的遗传结构,预期的3-4倍图谱扩展,基因座之间的低水平非同线关联,以及所有77个菌株之间的完全独立性。虽然亲本近交系--近交长睡眠(ILS)和近交短睡眠(ISS)--最初是通过从8向异质原种中选择获得的,该8向异质原种选择对乙醇的镇静作用具有不同的敏感性,但LXS组也分离了许多其他性状。因此,LXS面板提供了一个强大的新资源,用于在许多系统和学科中绘制复杂的性状,并应证明在模拟人类复杂疾病的遗传学方面具有很大的实用性。
The set of LXS recombinant inbred (RI) strains is a new and exceptionally large mapping panel that is suitable for the analysis of complex traits with comparatively high power. This panel consists of 77 strains-more than twice the size of other RI sets- and will typically provide sufficient statistical power (beta = 0.8) to map quantitative trait loci (QTLs) that account for similar to25% of genetic variance with a genomewide p < 0.05. To characterize the genetic architecture of this new set of RI strains, we genotyped 330 MIT microsatellite markers distributed on all autosomes and the X Chromosome and assembled error-checked meiotic recombination maps that have an average F-2-adjusted marker spacing of similar to4 cM. The LXS panel has a genetic structure consistent with random segregation and subsequent fixation of alleles, the expected 3-4 x map expansion, a low level of nonsyntenic association among loci, and complete independence among all 77 strains. Although the parental inbred strains-Inbred Long-Sleep (ILS) and Inbred Short-Sleep (ISS)-were derived originally by selection from an 8-way heterogeneous stock selected for differential sensitivity to sedative effects of ethanol, the LXS panel is also segregating for many other traits. Thus, the LXS panel provides a powerful new resource for mapping complex traits across many systems and disciplines and should prove to be of great utility in modeling the genetics of complex diseases in human populations.