Targeted identification and purging of deleterious genetic variants has been proposed as a novel approach to animal and plant breeding. This strategy is motivated, in part, by the observation that demographic events and strong selection associated with cultivated species pose a "cost of domestication." This includes an increase in the proportion of genetic variants that are likely to reduce fitness. Recent advances in DNA resequencing and sequence constraint-based approaches to predict the functional impact of a mutation permit the identification of putatively deleterious SNPs (dSNPs) on a genome-wide scale. Using exome capture resequencing of 21 barley lines, we identified 3855 dSNPs among 497,754 total SNPs. We generated whole-genome resequencing data of Hordeum murinum ssp. glaucum as a phylogenetic outgroup to polarize SNPs as ancestral vs. derived. We also observed a higher proportion of dSNPs per synonymous SNPs (sSNPs) in low-recombination regions of the genome. Using 5215 progeny from a genomic prediction experiment, we examined the fate of dSNPs over three breeding cycles. Adjusting for initial frequency, derived alleles at dSNPs reduced in frequency or were lost more often than other classes of SNPs. The highest-yielding lines in the experiment, as chosen by standard genomic prediction approaches, carried fewer homozygous dSNPs than randomly sampled lines from the same progeny cycle. In the final cycle of the experiment, progeny selected by genomic prediction had a mean of 5.6% fewer homozygous dSNPs relative to randomly chosen progeny from the same cycle.

中文翻译：

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大麦基因组预测群体中有害变异的命运。

有针对性地识别和清除有害遗传变异已被提议作为动植物育种的一种新方法。这一策略的部分动机是观察到人口事件和与栽培物种相关的强烈选择构成了“驯化成本”。这包括可能降低健康水平的遗传变异比例的增加。DNA 重测序和基于序列约束的方法的最新进展可预测突变的功能影响，从而可以在全基因组范围内识别假定有害的 SNP (dSNP)。通过对 21 个大麦品系进行外显子组捕获重测序，我们在 497,754 个 SNP 总数中鉴定出了 3855 个 dSNP。我们生成了Hordeum murinum ssp的全基因组重测序数据。glaucum作为系统发育外群，将 SNP 分为祖先与衍生。我们还观察到，在基因组的低重组区域中，每个同义 SNP (sSNP) 的 dSNP 比例较高。使用基因组预测实验中的 5215 个后代，我们检查了 dSNP 在三个育种周期中的命运。调整初始频率后，dSNP 的衍生等位基因频率降低，或者比其他类别的 SNP 更容易丢失。通过标准基因组预测方法选择的实验中产量最高的品系，与来自同一子代周期的随机采样品系相比，携带更少的纯合 dSNP。在实验的最后一个周期中，相对于同一周期中随机选择的后代，通过基因组预测选择的后代的纯合 dSNP 平均减少 5.6%。