The pig breeding system provides a unique framework to study recessive defects and the consequence on the phenotype. We examined a commercial synthetic Duroc population for recessive defects and identified a haplotype on chromosome 9 significantly affecting pre-weaning mortality. To identify the causal variant underlying the mortality, we examined sequence data of four carrier animals and 21 non-carrier animals from the same population. The results yield a strong candidate causal stop-gained variant (NM_001099928.1:c.541C>T) affecting the MYO7A gene in complete linkage disequilibrium with the lethal haplotype. The variant leads to an impaired (p.Gln181*) MYO7A protein that truncates 2032 amino acids from the protein. We examined a litter from a carrier sow inseminated by a carrier boar. From the resulting piglets, two confirmed homozygous piglets suffered from severe balance difficulties and the inability to walk properly. The variant segregates at a carrier frequency of 8.2% in the evaluated population and will be gradually purged from the population, improving animal welfare. Finally, this 'natural knockout' will increase our understanding of the functioning of the MYO7A gene and provides a potential model for Usher syndrome in humans.

中文翻译：

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MYO7A 基因的自然敲除导致仔猪断奶前死亡率

猪育种系统提供了一个独特的框架来研究隐性缺陷及其对表型的影响。我们检查了商业合成杜洛克种群的隐性缺陷，并在 9 号染色体上发现了一个显着影响断奶前死亡率的单倍型。为了确定死亡率背后的因果变异，我们检查了来自同一种群的 4 只携带动物和 21 只非携带动物的序列数据。结果产生了一个影响MYO7A的强候选因果停止增益变体 (NM_001099928.1:c.541C>T)基因与致死单倍型完全连锁不平衡。该变体导致受损的 (p.Gln181*) MYO7A 蛋白截断了该蛋白的 2032 个氨基酸。我们检查了一窝由载体公猪授精的载体母猪。从由此产生的仔猪中，有两只确认的纯合仔猪患有严重的平衡困难和无法正常行走。该变体在评估种群中以 8.2% 的携带频率分离，并将逐渐从种群中清除，从而改善动物福利。最后，这种“自然敲除”将增加我们对MYO7A基因功能的理解，并为人类亚瑟综合征提供一个潜在的模型。