Methods for Human Demographic Inference Using Haplotype Patterns From Genomewide Single-Nucleotide Polymorphism Data
Methods for Human Demographic Inference Using Haplotype Patterns From Genomewide Single-Nucleotide Polymorphism Data
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DOI：
10.1534/genetics.108.099275
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发表时间：
2009-05-01
期刊：
影响因子：
3.3
通讯作者：
Clark, Andrew G.
中科院分区：
文献类型：
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作者：
Lohmueller, Kirk E.;Bustamante, Carlos D.;Clark, Andrew G.
我们提出了一种新的近似似然方法来拟合人口统计模型，以人类全基因组单核苷酸多态性（SNP）数据。我们将基因组划分为恒定遗传图谱宽度的窗口，然后将不同的数目列表。单倍型和频率最多。每个窗口的共同单倍型。我们总结了这两种寄生虫的全基因组联合分布的数据，称为HCN统计。聚结模拟用于生成不同人口统计参数的预期HCN统计。HCN统计提供了额外的信息，用于解开复杂的人口统计数据以外的基于单SNP频率。我们的方法模拟数据的应用表明，它可以可靠地推断参数的增长和瓶颈模型，即使在重组热点的存在下，正确建模。我们还研究了全基因组数据集的实际问题，如遗传图谱中的错误，单倍型相位不确定性和SNP确定偏差，如何影响我们的方法。我们的方法的几个修改服务，使这些问题的鲁棒性。我们已经将我们的方法应用于Perlegen Sciences收集的数据，并找到了欧洲西北部人口规模从32，500 - 47，500年前开始严重减少的证据。
We propose a novel approximate-likelihood method to fit demographic models to human genomewide single-nucleotide polymorphism (SNP) data. We divide the genome into windows of constant genetic map width and then tabulate the number of distinct. haplotypes and the frequency of the most. common haplotype for each window. We summarize the data by the genomewide joint distribution of these two statistics-termed the HCN statistic. Coalescent simulations are used to generate the expected HCN statistic for different demographic parameters. The HCN statistic provides additional information for disentangling complex demography beyond statistics based on single-SNP frequencies. Application of our method to simulated data shows it can reliably infer parameters from growth and bottleneck models, even in the presence of recombination hotspots when properly modeled. We also examined how practical problems with genomewide data sets, such as errors in the genetic map, haplotype phase uncertainty, and SNP ascertainment bias, affect our method. Several modifications of our method served to make it robust to these problerns. We have applied our method to data collected by Perlegen Sciences and find evidence for a severe population size reduction in northwestern Europe starting 32,500-47,500 years ago.