Genomic scans for selective sweeps using SNP data
Genomic scans for selective sweeps using SNP data
复制标题
DOI：
10.1101/gr.4252305
复制
发表时间：
2005-11-01
期刊：
影响因子：
7
通讯作者：
Bustamante, C
中科院分区：
文献类型：
--
作者：
Nielsen, R;Williamson, S;Bustamante, C
从基因组SNP数据检测选择性扫描由于用于发现SNP的复杂确定方案以及潜在的复杂人口统计学和变化的突变和重组率的混杂影响而变得复杂。目前用于检测选择性扫描的方法对人口统计学假设和变化的重组率几乎没有鲁棒性，并且没有提供用于校正确定偏差的方法。在这里，我们提出了几个新的测试，旨在检测基因组SNP数据的选择性扫描。使用广泛的模拟，我们表明，一个新的参数测试，基于复合似然，具有很高的权力，以检测选择性扫描，是令人惊讶的鲁棒性有关重组率和人口统计学的假设（即，低I型错误）。我们的新测试还提供了选择性扫描的位置和选择系数的大小的估计。为了说明该方法，我们将我们的方法应用于来自西雅图SNP项目的数据和来自HapMap项目的2号染色体数据。在2号染色体中，最极端的信号出现在乳糖酶基因中，该基因此前已被证明正在经历正选择。在许多其他区域也发现了选择性扫描的证据，包括已知与疾病风险相关的基因，如DPP10和COL4A3。
Detecting selective sweeps from genomic SNP data is complicated by the intricate ascertainment schemes used to discover SNPs, and by the confounding influence of the underlying complex demographics and varying Mutation and recombination rates. Current methods for detecting selective sweeps have little or no robustness to the demographic assumptions and varying recombination rates, and provide no method for correcting for ascertainment biases. Here, we present several new tests aimed at detecting selective sweeps from genomic SNP data. Using extensive simulations, we show that a new parametric test, based on composite likelihood, has a high power to detect selective sweeps and is Surprisingly robust to assumptions regarding recombination rates and demography (i.e., has low Type I error). Our new test also provides estimates of the location of the selective sweep(s) and the magnitude of the selection coefficient. To illustrate the method, we apply our approach to data from the Seattle SNP project and to Chromosome 2 data from the HapMap project. In Chromosome 2, the most extreme signal is found in the lactase gene, which previously has been shown to be undergoing positive selection. Evidence for selective sweeps is also found in many other regions, including genes known to be associated with disease risk such as DPP10 and COL4A3.