High-resolution population-specific recombination rates and their effect on phasing and genotype imputation.
High-resolution population-specific recombination rates and their effect on phasing and genotype imputation.
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高分辨率群体特异性重组率及其对定相和基因型插补的影响。
DOI：
10.1038/s41431-020-00768-8
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发表时间：
2021-04
期刊：
影响因子：
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通讯作者：
Ripatti S
中科院分区：
文献类型：
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作者：
Hassan S;Surakka I;Taskinen MR;Salomaa V;Palotie A;Wessman M;Tukiainen T;Pirinen M;Palta P;Ripatti S
先前的研究表明，使用特定群体的参考组合对下游群体基因组分析（例如单倍型定相、基因型插补和关联）具有显着影响，特别是在群体分离的背景下。在这里，我们使用来自芬兰的 55 个家庭三人组的高覆盖率 (20–30×) 全基因组测序数据开发了 10 和 50 kb 尺度的高分辨率重组率图谱，并将其与非芬兰欧洲人 (NFE) 的重组率进行了比较。与使用基于 NFE 的重组率进行的相同分析相比，我们测试了芬兰人统计定相和基因型插补中特定人群重组率的下游影响。我们发现芬兰重组率与 NFE 具有较高的相关性（Spearman’s ρ = 0.67–0.79），尽管平均而言（在所有常染色体上），芬兰重组率 (2.268 ± 0.4209 cM/Mb) 比 NFE 低 12–14% (2.641 ±0.5032 cM/Mb)。发现芬兰重组图谱对单倍型定相准确性（转换错误率约 2%）和平均插补一致性率（常见变异为 97-98%，低频变异为 92-96%，罕见变异为 78-90%）没有显着影响。我们的结果表明，单倍型定相和基因型插补主要取决于特定人群的背景，例如适当的参考面板及其样本大小，但不依赖于特定人群的重组图谱。尽管重组率估计在芬兰和 NFE 人群之间存在一些差异，但单倍型分析和插补并未受到所使用的重组图谱的明显影响。因此，目前可用的 HapMap 重组图对于特定人群的分期和插补流程似乎很稳健，即使是在像芬兰这样相对孤立的人群的背景下也是如此。
Previous research has shown that using population-specific reference panels has a significant effect on downstream population genomic analyses like haplotype phasing, genotype imputation, and association, especially in the context of population isolates. Here, we developed a high-resolution recombination rate mapping at 10 and 50 kb scale using high-coverage (20–30×) whole-genome sequenced data of 55 family trios from Finland and compared it to recombination rates of non-Finnish Europeans (NFE). We tested the downstream effects of the population-specific recombination rates in statistical phasing and genotype imputation in Finns as compared to the same analyses performed by using the NFE-based recombination rates. We found that Finnish recombination rates have a moderately high correlation (Spearman’s ρ = 0.67–0.79) with NFE, although on average (across all autosomal chromosomes), Finnish rates (2.268 ± 0.4209 cM/Mb) are 12–14% lower than NFE (2.641 ± 0.5032 cM/Mb). Finnish recombination map was found to have no significant effect in haplotype phasing accuracy (switch error rates ~2%) and average imputation concordance rates (97–98% for common, 92–96% for low frequency and 78–90% for rare variants). Our results suggest that haplotype phasing and genotype imputation mostly depend on population-specific contexts like appropriate reference panels and their sample size, but not on population-specific recombination maps. Even though recombination rate estimates had some differences between the Finnish and NFE populations, haplotyping and imputation had not been noticeably affected by the recombination map used. Therefore, the currently available HapMap recombination maps seem robust for population-specific phasing and imputation pipelines, even in the context of relatively isolated populations like Finland.