Multiple locus linkage analysis of genomewide expression in yeast.
Multiple locus linkage analysis of genomewide expression in yeast.
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DOI：
10.1371/journal.pbio.0030267
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发表时间：
2005-08
期刊：
影响因子：
9.8
通讯作者：
Kruglyak L
中科院分区：
文献类型：
--
作者：
Storey JD;Akey JM;Kruglyak L
随着从单个生物样本中测量数千个相关表型的能力，现在从基因上剖析系统级生物现象是可行的。转录调控和蛋白质丰度的遗传学可能是复杂的，这意味着多个基因座的遗传变异将影响这些表型。最近的几项研究通过将传统的连锁分析方法应用于全基因组表达数据来研究遗传变异在转录中的作用，其中每个基因表达水平被视为一个数量性状，并相互独立地进行分析。在这里，我们开发了一种新的、计算高效的方法来同时定位多个基因表达数量性状基因座，该方法直接使用所有可用的数据。在基因表达特征之间共享的信息是以一种对数据的统计特性做出最小假设的方式获取的。该方法为单个基因座和为给定的表达性状选择的多个基因座的整体联合重要性提供了易于解释的统计意义的度量。我们将新方法应用于两个萌芽酵母菌株之间的杂交，并估计至少37%的所有基因表达性状显示出两个同时连锁，其中我们考虑了上位性相互作用。对170个基因表达性状的联合连锁数量性状基因座进行了高度可信的鉴定，预计这两个基因座对至少153个性状都是真阳性。此外，我们能够证明上位性互作对至少14%的所有性状的基因表达差异有贡献。我们将所提出的方法与对所有对基因座进行详尽的二维扫描进行了比较。令人惊讶的是，我们证明了详尽的二维扫描不如这里使用的顺序搜索那么强大。此外，我们还表明，二维扫描并不能真正地测试同时连锁，而且从现有方法测量的统计意义不能在许多性状中解释。复杂性状往往受多个基因座控制。这种新方法可以同时定位酿酒酵母中的多个基因表达数量性状基因座，并评估它们的重要性。
With the ability to measure thousands of related phenotypes from a single biological sample, it is now feasible to genetically dissect systems-level biological phenomena. The genetics of transcriptional regulation and protein abundance are likely to be complex, meaning that genetic variation at multiple loci will influence these phenotypes. Several recent studies have investigated the role of genetic variation in transcription by applying traditional linkage analysis methods to genomewide expression data, where each gene expression level was treated as a quantitative trait and analyzed separately from one another. Here, we develop a new, computationally efficient method for simultaneously mapping multiple gene expression quantitative trait loci that directly uses all of the available data. Information shared across gene expression traits is captured in a way that makes minimal assumptions about the statistical properties of the data. The method produces easy-to-interpret measures of statistical significance for both individual loci and the overall joint significance of multiple loci selected for a given expression trait. We apply the new method to a cross between two strains of the budding yeast Saccharomyces cerevisiae, and estimate that at least 37% of all gene expression traits show two simultaneous linkages, where we have allowed for epistatic interactions. Pairs of jointly linking quantitative trait loci are identified with high confidence for 170 gene expression traits, where it is expected that both loci are true positives for at least 153 traits. In addition, we are able to show that epistatic interactions contribute to gene expression variation for at least 14% of all traits. We compare the proposed approach to an exhaustive two-dimensional scan over all pairs of loci. Surprisingly, we demonstrate that an exhaustive two-dimensional scan is less powerful than the sequential search used here. In addition, we show that a two-dimensional scan does not truly allow one to test for simultaneous linkage, and the statistical significance measured from this existing method cannot be interpreted among many traits. Complex traits are frequently under control of multiple loci. This new method simultaneously maps multiple gene expression quantitative trait loci and assesses their significance within Saccharomyces cerevisiae.
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影响因子：
2.1
作者：
Newton, MA;Noueiry, A;Ahlquist, P
通讯作者：
Ahlquist, P
影响因子：
30.8
作者：
Cowles, CR;Hirschhorn, JN;Lander, ES
通讯作者：
Lander, ES
影响因子：
30.8
作者：
Oleksiak, MF;Churchill, GA;Crawford, DL
通讯作者：
Crawford, DL
影响因子：
5.3
作者：
Fazzio, TG;Kooperberg, C;Tsukiyama, T
通讯作者：
Tsukiyama, T
DOI：
10.1111/1467-9868.00354
发表时间：
2002-01-01
影响因子：
5.8
作者：
Broman, KW;Speed, TP
通讯作者：
Speed, TP