Genome Reshuffling for Advanced Intercross Permutation (GRAIP): simulation and permutation for advanced intercross population analysis.
Genome Reshuffling for Advanced Intercross Permutation (GRAIP): simulation and permutation for advanced intercross population analysis.
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DOI：
10.1371/journal.pone.0001977
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发表时间：
2008-04-23
期刊：
影响因子：
3.7
通讯作者：
Williams RW
中科院分区：
文献类型：
--
作者：
Peirce JL;Broman KW;Lu L;Chesler EJ;Zhou G;Airey DC;Birmingham AE;Williams RW
高级互交系（AIL）是使用多代育种方案创建的分离群体，用于精细定位小鼠和其他生物体中的复杂性状基因座（QTL）。应用QTL作图方法进行互交和回交群体，通常随后进行个体和表型的简单排列，不能解释AIL家族结构的影响，其中最后世代已经扩大，并导致不适当的低显著性阈值。AIL群体中朴素作图方法的关键问题是个体不是可交换的单位。家庭结构的影响有直接的影响，最佳的AIL创建（许多杂交，每交很少的动物，和人口扩张前的最后一代），我们讨论这些和效用的AIL群体QTL精细定位。我们还描述了基因组重排高级交叉排列，（GRAIP）的方法分析AIL数据，占家庭结构。GRAIP在最后一代杂交中置换一个更可互换的单位-亲本基因组-并基于交换的亲本身份模拟置换的AIL群体的再生。GRAIP为AIL和其他具有相似家族结构的人群确定适当的全基因组显著性阈值和位点特异性P值。我们使用一个大的密集基因型小鼠AIL群体（来自32个杂交的1333个个体）将GRAIP与幼稚排列进行对比。使用毛色作为模型表型的幼稚排列显示出高的假阳性基因座识别和不确定的显著性水平，这是使用GRAIP校正的。GRAIP还检测到一个已建立的海马体重量位点和一个新的位点，Hipp 9a。GRAIP为AIL和其他具有相似家族结构的人群确定适当的全基因组显著性阈值和位点特异性P值。家庭结构的影响有直接的影响，最佳的AIL创建，我们讨论这些和AIL人口的效用。
Advanced intercross lines (AIL) are segregating populations created using a multi-generation breeding protocol for fine mapping complex trait loci (QTL) in mice and other organisms. Applying QTL mapping methods for intercross and backcross populations, often followed by naïve permutation of individuals and phenotypes, does not account for the effect of AIL family structure in which final generations have been expanded and leads to inappropriately low significance thresholds. The critical problem with naïve mapping approaches in AIL populations is that the individual is not an exchangeable unit. The effect of family structure has immediate implications for the optimal AIL creation (many crosses, few animals per cross, and population expansion before the final generation) and we discuss these and the utility of AIL populations for QTL fine mapping. We also describe Genome Reshuffling for Advanced Intercross Permutation, (GRAIP) a method for analyzing AIL data that accounts for family structure. GRAIP permutes a more interchangeable unit in the final generation crosses – the parental genome – and simulating regeneration of a permuted AIL population based on exchanged parental identities. GRAIP determines appropriate genome-wide significance thresholds and locus-specific P-values for AILs and other populations with similar family structures. We contrast GRAIP with naïve permutation using a large densely genotyped mouse AIL population (1333 individuals from 32 crosses). A naïve permutation using coat color as a model phenotype demonstrates high false-positive locus identification and uncertain significance levels, which are corrected using GRAIP. GRAIP also detects an established hippocampus weight locus and a new locus, Hipp9a. GRAIP determines appropriate genome-wide significance thresholds and locus-specific P-values for AILs and other populations with similar family structures. The effect of family structure has immediate implications for the optimal AIL creation and we discuss these and the utility of AIL populations.
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影响因子：
5.3
作者：
Lu, L;Airey, DC;Williams, RW
通讯作者：
Williams, RW
影响因子：
2.5
作者：
Peirce, JL;Chesler, EJ;Lu, L
通讯作者：
Lu, L
影响因子：
30.8
作者：
Chesler, EJ;Lu, L;Williams, RW
通讯作者：
Williams, RW
影响因子：
3
作者：
Chesler, EJ;Wang, JT;Williams, RW
通讯作者：
Williams, RW
影响因子：
4.4
作者：
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通讯作者：
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