Department of Animal Science, University of California, Davis, CA, 95616, USA.
Department of Animal Science, University of Nebraska, Lincoln, NE, 68583, USA.
Genet Sel Evol. 2019 Aug 6;51(1):36. doi: 10.1186/s12711-019-0477-3.
Recessive loss-of-function (LOF) alleles at genes which are essential for life, can result in early embryonic mortality. Cattle producers can use the LOF carrier status of individual animals to make selection and mate allocation decisions.
Two beef cattle breeding strategies i.e. (1) selection against LOF carriers as parents and (2) simultaneous selection and mate allocation to avoid the occurrence of homozygous offspring in three scenarios, which differed in number and frequency of LOF alleles were evaluated using the mate selection program, MateSel. Scenarios included (a) seven loci with high-frequency LOF alleles, (b) 76 loci with low-frequency LOF alleles, and (c) 50 loci with random high- and low-frequency LOF alleles. In addition, any savings resulting from the information obtained by varying the percentage (0-100%) of the herd genotyped, together with segregation analysis to cover ungenotyped animals, were calculated to determine (1) which percentage optimized net profit for a fixed cost of genotyping ($30/test), and (2) the breakeven cost for genotyping.
With full knowledge of the LOF alleles carried by selection candidates, the most profitable breeding strategy was always simultaneous selection and mate allocation to avoid homozygous affected offspring (aa) as compared to indiscriminate selection against carrier parents (Aa). The breakeven value of genotyping depended on the number of loci modeled, the LOF allele frequencies, and the mating/selection strategies used. Genotyping was most valuable when it was used to avoid otherwise high levels of embryonic mortalities. As the number of essential loci with LOF alleles increased, especially when some were present at relatively high minor allele frequencies, embryonic losses increased, and profit was maximized by genotyping 10 to 20% of a herd and using that information to reduce these losses.
Genotyping 100% of the herd was never the most profitable outcome in any scenario; however, genotyping some proportion of the herd, together with segregation analysis to cover ungenotyped animals, maximized overall profit in scenarios with large numbers of loci with LOF alleles. As more LOF alleles are identified, such a mate selection software will likely be required to optimally select and allocate matings to balance the rate of genetic gain, embryonic losses, and inbreeding.
对于生命必需的基因,如果隐性失活(LOF)等位基因发生突变,可能会导致胚胎早期死亡。牛养殖者可以利用个体动物的 LOF 携带状态来做出选择和配种决策。
使用配种选择程序 MateSel 评估了两种肉牛育种策略,即(1)选择不携带 LOF 等位基因的个体作为父母,以及(2)在三种情况下同时进行选择和配种,以避免纯合子后代的出现,这三种情况在 LOF 等位基因的数量和频率上有所不同。方案包括(a)7 个具有高频 LOF 等位基因的基因座,(b)76 个具有低频 LOF 等位基因的基因座,以及(c)50 个具有随机高频和低频 LOF 等位基因的基因座。此外,还计算了通过改变 0-100%的牛群进行基因分型的百分比而获得的任何节省,以及覆盖未基因分型动物的分离分析,以确定(1)对于固定的基因分型成本($30/测试),哪个百分比优化了净收益,以及(2)基因分型的盈亏平衡点。
通过完全了解候选个体所携带的 LOF 等位基因,与盲目选择携带 LOF 等位基因的父母(Aa)相比,最有利可图的育种策略始终是同时进行选择和配种,以避免纯合子受影响的后代(aa)。基因分型的盈亏平衡点取决于建模的基因座数量、LOF 等位基因频率以及使用的交配/选择策略。当基因分型用于避免胚胎死亡率较高的情况时,其价值最大。随着具有 LOF 等位基因的必需基因座数量的增加,特别是当其中一些基因座具有相对较高的次要等位基因频率时,胚胎损失会增加,通过基因分型 10-20%的牛群并利用这些信息来减少这些损失,可以实现最大利润。
在任何情况下,对 100%的牛群进行基因分型都不是最有利可图的结果;然而,对部分牛群进行基因分型,同时利用分离分析覆盖未基因分型的动物,在具有大量具有 LOF 等位基因的基因座的情况下,最大化了整体利润。随着越来越多的 LOF 等位基因被识别,可能需要使用这种配种选择软件来最佳地选择和分配配种,以平衡遗传增益、胚胎损失和近亲繁殖的速度。