It is expected that functional, mainly missense and loss-of-function (LOF), and regulatory variants are responsible for most phenotypic differences between breeds and genetic lines of livestock species that have undergone diverse selection histories. However, there is still limited knowledge about the existing missense and LOF variation in commercial livestock populations, in particular regarding population-specific variation and how it can affect applications such as across-breed genomic prediction. We re-sequenced the whole genome of 7848 individuals from nine commercial pig lines (average sequencing coverage: 4.1×) and imputed whole-genome genotypes for 440,610 pedigree-related individuals. The called variants were categorized according to predicted functional annotation (from LOF to intergenic) and prevalence level (number of lines in which the variant segregated; from private to widespread). Variants in each category were examined in terms of their distribution along the genome, alternative allele frequency, per-site Wright’s fixation index (FST), individual load, and association to production traits. Of the 46 million called variants, 28% were private (called in only one line) and 21% were widespread (called in all nine lines). Genomic regions with a low recombination rate were enriched with private variants. Low-prevalence variants (called in one or a few lines only) were enriched for lower allele frequencies, lower FST, and putatively functional and regulatory roles (including LOF and deleterious missense variants). On average, individuals carried fewer private deleterious missense alleles than expected compared to alleles with other predicted consequences. Only a small subset of the low-prevalence variants had intermediate allele frequencies and explained small fractions of phenotypic variance (up to 3.2%) of production traits. The significant low-prevalence variants had higher per-site FST than the non-significant ones. These associated low-prevalence variants were tagged by other more widespread variants in high linkage disequilibrium, including intergenic variants. Most low-prevalence variants have low minor allele frequencies and only a small subset of low-prevalence variants contributed detectable fractions of phenotypic variance of production traits. Accounting for low-prevalence variants is therefore unlikely to noticeably benefit across-breed analyses, such as the prediction of genomic breeding values in a population using reference populations of a different genetic background.

中文翻译：

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猪系中罕见且特定于人群的功能变异

预计功能性，主要是错义和功能丧失 (LOF) 和调节变异是导致经历了不同选择历史的牲畜品种和遗传系之间的大多数表型差异的原因。然而，关于商业牲畜种群中现有的错义和 LOF 变异的知识仍然有限，特别是关于种群特异性变异以及它如何影响跨品种基因组预测等应用。我们对来自 9 个商业猪系的 7848 个个体的全基因组进行了重新测序（平均测序覆盖率：4.1 倍），并对 440,610 个谱系相关个体的全基因组基因型进行了估算。被调用的变体根据预测的功能注释（从 LOF 到基因间）和流行水平（变体分离的系数；从私有到广泛）进行分类。对每个类别的变异体在基因组中的分布、替代等位基因频率、每位点赖特固定指数 (FST)、个体负荷和与生产性状的关联进行了检查。在 4600 万个被调用的变体中，28% 是私有的（仅在一行中调用），21% 是广泛的（在所有九行中调用）。重组率低的基因组区域富含私有变体。低流行变体（仅在一行或几行中调用）因较低的等位基因频率、较低的 FST 和推定的功能和调节作用（包括 LOF 和有害的错义变体）而富集。一般，与具有其他预测后果的等位基因相比，个体携带的私人有害错义等位基因少于预期。只有一小部分低流行变体具有中等等位基因频率，并解释了生产性状的一小部分表型变异（高达 3.2%）。显着的低流行变体比不显着的变体具有更高的每个站点 FST。这些相关的低流行变体被高度连锁不平衡中其他更广泛的变体标记，包括基因间变体。大多数低流行变体具有较低的次要等位基因频率，并且只有一小部分低流行变体贡献了生产性状表型变异的可检测部分。因此，考虑低流行变体不太可能显着受益于跨品种分析，