Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences, Northwest University, Xi'an, China.
Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China.
Mol Ecol Resour. 2019 Sep;19(5):1240-1253. doi: 10.1111/1755-0998.13036. Epub 2019 Aug 1.
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-typer V1.1, is freely available at https://github.com/huangkang1987/mhc-typer.
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，可以用一对引物进行共同扩增。这导致基因分型困难和分析不准确。在这里，我们提出了一种在重复基因座的扩增中为不同基因座分配等位基因的方法。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。这些因素包括基因座之间相同等位基因的共享、无效等位基因、拷贝数变异、负扩增、杂合子过剩或杂合子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，并加权以估计等位基因频率。计算等位基因配置的可能性，并使用启发式算法进行优化。蒙特卡罗模拟和三个经验 MHC 数据集被用作示例，以评估我们的方法在不同条件下的功效。我们的新软件 mhc-typer V1.1 可在 https://github.com/huangkang1987/mhc-typer 上免费获得。
