Centre for Genetic Improvement of Livestock, Department of Animal Biosciences, University of Guelph, Guelph N1G 2W1, Ontario, Canada; Departament de Ciència Animal i dels Aliments, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain.
Centre for Genetic Improvement of Livestock, Department of Animal Biosciences, University of Guelph, Guelph N1G 2W1, Ontario, Canada.
J Dairy Sci. 2019 Apr;102(4):3175-3188. doi: 10.3168/jds.2018-15296. Epub 2019 Feb 7.
Realized deviations from the expected Mendelian inheritance of alleles from heterozygous parents have been previously reported in a broad range of organisms (i.e., transmission ratio distortion; TRD). Various biological mechanisms affecting gametes, embryos, fetuses, or even postnatal offspring can produce patterns of TRD. However, knowledge about its prevalence and potential causes in livestock species is still scarce. Specific Bayesian models have been recently developed for the analyses of TRD for biallelic loci, which accommodated a wide range of population structures, enabling TRD investigation in livestock populations. The parameterization of these models is flexible and allows the study of overall (parent-unspecific) TRD and sire- and dam-specific TRD. This research aimed at deriving Bayesian models for fitting TRD on the basis of haplotypes, testing the models for both haplotype- and SNP-based methods in simulated data and actual Holstein genotypes, and developing a specific software for TRD analyses. Results obtained on simulated data sets showed that the statistical power of the analysis increased with sample size of trios (n), proportion of heterozygous parents, and the magnitude of the TRD. On the other hand, the statistical power to detect TRD decreased with the number of alleles at each loci. Bayesian analyses showed a strong Pearson correlation coefficient (≥0.97) between simulated and estimated TRD that reached the significance level of Bayes factor ≥10 for both single-marker and haplotype analyses when n ≥ 25. Moreover, the accuracy in terms of the mean absolute error decreased with the increase of the sample size and increased with the number of alleles at each loci. Using real data (55,732 genotypes of Holstein trios), SNP- and haplotype-based distortions were detected with overall TRD, sire-TRD, or dam-TRD, showing different magnitudes of TRD and statistical relevance. Additionally, the haplotype-based method showed more ability to capture TRD compared with individual SNP. To discard possible random TRD in real data, an approximate empirical null distribution of TRD was developed. The program TRDscan v.1.0 was written in Fortran 2008 language and provides a powerful statistical tool to scan for TRD regions across the whole genome. This developed program is freely available at http://www.casellas.info/files/TRDscan.zip.
从杂合父母中预期的孟德尔遗传等位基因的实际偏差已经在广泛的生物体中被报道过（即，传递比失真；TRD）。影响配子、胚胎、胎儿，甚至产后后代的各种生物学机制可以产生 TRD 的模式。然而，关于其在牲畜物种中的普遍性和潜在原因的知识仍然匮乏。最近已经为双等位基因座的 TRD 分析开发了特定的贝叶斯模型，这些模型适应了广泛的群体结构，使 TRD 能够在牲畜群体中进行研究。这些模型的参数化具有灵活性，并且允许研究总体（父母特异性）TRD 以及父本和母本特异性 TRD。本研究旨在基于单倍型推导出拟合 TRD 的贝叶斯模型，在模拟数据和实际荷斯坦基因型中测试基于单倍型和 SNP 的方法的模型，并开发特定的 TRD 分析软件。在模拟数据集上获得的结果表明，分析的统计能力随着三亲体（n）的样本大小、杂合父母的比例和 TRD 的幅度而增加。另一方面，检测 TRD 的统计能力随着每个位点的等位基因数量的减少而降低。贝叶斯分析显示，模拟和估计的 TRD 之间具有很强的皮尔逊相关系数（≥0.97），当 n≥25 时，无论是单标记还是单倍型分析，贝叶斯因子≥10 都达到了显著水平。此外，准确性（以平均绝对误差衡量）随着样本量的增加而降低，并且随着每个位点的等位基因数量的增加而增加。使用真实数据（55732 个荷斯坦三亲体的基因型），检测到了 SNP 和单倍型的总体 TRD、父本 TRD 或母本 TRD 扭曲，显示出不同程度的 TRD 和统计学相关性。此外，与单个 SNP 相比，基于单倍型的方法具有更强的捕获 TRD 的能力。为了排除真实数据中可能的随机 TRD，开发了一个 TRD 的近似经验零分布。程序 TRDscan v.1.0 是用 Fortran 2008 语言编写的，提供了一个强大的统计工具，可以在整个基因组范围内扫描 TRD 区域。这个开发的程序可以在 http://www.casellas.info/files/TRDscan.zip 免费获得。
