DataSheet1_Parent-offspring genotyped trios unravelling genomic regions with gametic and genotypic epistatic transmission bias on the cattle genome.zip

Several biological mechanisms affecting the sperm and ova fertility and viability at developmental stages of the reproductive cycle resulted in observable transmission ratio distortion (i.e., deviation from Mendelian expectations). Gene-by-gene interactions (or epistasis) could also potentially cause specific transmission ratio distortion patterns at different loci as unfavorable allelic combinations are under-represented, exhibiting deviation from Mendelian proportions. Here, we aimed to detect pairs of loci with epistatic transmission ratio distortion using 283,817 parent-offspring genotyped trios (sire-dam-offspring) of Holstein cattle. Allelic and genotypic parameterization for epistatic transmission ratio distortion were developed and implemented to scan the whole genome. Different epistatic transmission ratio distortion patterns were observed. Using genotypic models, 7, 19 and 6 pairs of genomic regions were found with decisive evidence with additive-by-additive, additive-by-dominance/dominance-by-additive and dominance-by-dominance effects, respectively. Using the allelic transmission ratio distortion model, more insight was gained in understanding the penetrance of single-locus distortions, revealing 17 pairs of SNPs. Scanning for the depletion of individuals carrying pairs of homozygous genotypes for unlinked loci, revealed 56 pairs of SNPs with recessive epistatic transmission ratio distortion patterns. The maximum number of expected homozygous offspring, with none of them observed, was 23. Finally, in this study, we identified candidate genomic regions harboring epistatic interactions with potential biological implications in economically important traits, such as reproduction.

多种影响生殖周期不同发育阶段精子与卵子受精能力及存活状态的生物学机制，可导致可观测的传递比率偏倚（transmission ratio distortion）。基因间互作（上位性，epistasis）亦可能在不同基因座上引发特定的传递比率偏倚模式：由于不利的等位基因组合占比偏低，整体呈现出偏离孟德尔遗传比例的特征。本研究旨在利用283817头荷斯坦奶牛的亲代-子代基因分型三联家系（公畜-母畜-子代），检测存在上位性传递比率偏倚的基因座对。本研究开发并应用了针对上位性传递比率偏倚的等位基因与基因型参数化模型，用于全基因组扫描。研究中观测到多种不同的上位性传递比率偏倚模式。借助基因型模型，分别在加性×加性、加性×显性/显性×加性以及显性×显性效应下，鉴定出7、19和6组具备决定性统计学证据的基因组区域对。借助等位基因传递比率偏倚模型，研究进一步阐明了单基因座偏倚的外显率，并鉴定出17组单核苷酸多态性（single nucleotide polymorphisms, SNPs）对。通过扫描非连锁基因座的纯合基因型携带个体的缺失情况，本研究鉴定出56组具有隐性上位性传递比率偏倚模式的SNPs对。理论预期存在的纯合子子代最大数量为23，但实际未观测到任何此类个体。最终，本研究鉴定出了携带上位性互作的候选基因组区域，这些互作可能对繁殖等经济重要性状具有潜在生物学影响。