Discovery and genotyping of genome structural polymorphism by sequencing on a population scale.
Discovery and genotyping of genome structural polymorphism by sequencing on a population scale.
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作者：
为了理解基因组变异在复杂疾病中的作用，需要对大群体中的基因组变异进行准确和完整的分析。我们提出了一个分析框架，在人群中的基因组缺失多态性的特征，使用分布在数百或数千个基因组的序列数据。我们的方法使用人口水平的关系，重新解释的技术特点，往往反映结构变异的序列数据。在1000个基因组项目试点中，这种方法识别了168个基因组的缺失多态性（以4倍平均覆盖率测序），其灵敏度和特异性是其他算法无法比拟的。我们还描述了一种方法来确定每个基因组中每个缺失多态性的等位基因状态或基因型; 1000个基因组计划使用这种方法在人群中以高精度对13，826个缺失多态性（48 bp - 960 kbp）进行分型。这些方法提供了一种将基因组结构多态性与人群中的复杂疾病联系起来的方法。
Accurate and complete analysis of genome variation in large populations will be required to understand the role of genome variation in complex disease. We present an analytical framework for characterizing genome deletion polymorphism in populations, using sequence data that are distributed across hundreds or thousands of genomes. Our approach uses population-level relationships to re-interpret the technical features of sequence data that often reflect structural variation. In the 1000 Genomes Project pilot, this approach identified deletion polymorphism across 168 genomes (sequenced at 4x average coverage) with sensitivity and specificity unmatched by other algorithms. We also describe a way to determine the allelic state or genotype of each deletion polymorphism in each genome; the 1000 Genomes Project used this approach to type 13,826 deletion polymorphisms (48 bp – 960 kbp) at high accuracy in populations. These methods offer a way to relate genome structural polymorphism to complex disease in populations.