Assigning alleles to different loci in amplifications of duplicated loci
Assigning alleles to different loci in amplifications of duplicated loci
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在重复基因座的扩增中将等位基因分配给不同的基因座
DOI：
10.1111/1755-0998.13036
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发表时间：
2019-08-01
影响因子：
7.7
通讯作者：
Li，Baoguo
中科院分区：
文献类型：
--
作者：
Huang，Kang;Zhang，Pei;Li，Baoguo
重复的基因座，例如与主要组织相容性复合体（MHC）基因相关的基因座，通常具有相似的DNA序列，可以用一对引物共扩增。这导致基因分型困难和不准确的分析。在这里，我们提出了一种在重复基因座的扩增中将等位基因分配到不同基因座的方法。该方法同时考虑了可能影响正确等位基因分配的几个因素。基因座间共用相同等位基因、等位基因无效、拷贝数变异、负扩增、杂合子过多或不足以及连锁不平衡。从每个个体的等位基因中提取可能的多位点基因型，并加权估计等位基因频率。计算等位基因配置的可能性，并用启发式算法进行优化。以蒙特卡罗模拟和三个经验MHC数据集为例，评估了我们的方法在不同条件下的有效性。我们的新软件mhc‐typer1.1可在https://github.com/huangkang1987/mhc-typer免费获得。
Duplicated loci, for example those associated with major histocompatibility complex (MHC) genes, often have similar DNA sequences that can be coamplified with a pair of primers. This results in genotyping difficulties and inaccurate analyses. Here, we present a method to assign alleles to different loci in amplifications of duplicated loci. This method simultaneously considers several factors that may each affect correct allele assignment. These are the sharing of identical alleles among loci, null alleles, copy number variation, negative amplification, heterozygote excess or heterozygote deficiency, and linkage disequilibrium. The possible multilocus genotypes are extracted from the alleles for each individual and weighted to estimate the allele frequencies. The likelihood of an allele configuration is calculated and is optimized with a heuristic algorithm. Monte‐Carlo simulations and three empirical MHC data sets are used as examples to evaluate the efficacy of our method under different conditions. Our new software,mhc‐typerV1.1, is freely available at https://github.com/huangkang1987/mhc-typer.