BACKGROUND Warmblood fragile foal syndrome (WFFS) is a monogenetic defect caused by a recessive lethal missense point mutation in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 gene (PLOD1, c.2032G>A). The majority of homozygous WFFS horses are aborted during gestation. Clinical signs of affected horses include fragile skin, skin and mucosa lacerations, hyperextension of the articulations, and hematomas. In spite of its harmful effect, a relatively high frequency of WFFS carriers has been found in Warmblood horses, suggesting a heterozygote advantage. Thus, in this study our aims were to: (1) estimate the frequency of WFFS carriers in the Swedish Warmblood breed (SWB), (2) estimate the effect of WFFS carrier genotype on performance traits in two SWB subpopulations bred for different disciplines, and (3) simulate the potential effects of balancing selection and different selection strategies on the frequency of carriers. METHODS In total, 2288 SWB sport horses born between 1971 and 2020 were tested for the WFFS mutation and had estimated breeding values (EBV) for ten traditional evaluating and 50 linear descriptive traits. RESULTS The frequency of WFFS carriers calculated from a pool of 511 randomly selected SWB horses born in 2017 was equal to 7.4% and ranged from 0.0 to 12.0% among the whole set of tested SWB horses, starting from 1971 till 2020. The effect of the WFFS carrier genotype was significant for several EBV mainly related to movements and dressage traits and especially for horses not bred for the show jumping discipline. Using simulation, we showed that balancing selection can maintain a recessive lethal allele in populations such as the SWB breed over generations and that the frequency is expected to slowly decrease in absence of balancing selection. Finally, we showed that selection against carrier sires can result in a more rapid decrease of the frequency of the mutant allele over time. CONCLUSION Further research is needed to confirm the apparent association between equine performance and the WFFS carrier genotype. Identification of such associations or new causative mutations for horse performance traits can serve as new tools in horse breeding to select for healthy, sustainable, and better performing horses.

中文翻译：

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瑞典温血马脆弱马驹综合征携带者的表现和育种前景。

背景温血脆性马驹综合征 (WFFS) 是由前胶原-赖氨酸、2-氧代戊二酸 5-双加氧酶 1 基因 (PLOD1, c.2032G>A) 中的隐性致死错义点突变引起的单基因缺陷。大多数纯合 WFFS 马在妊娠期间流产。受影响马的临床症状包括脆弱的皮肤、皮肤和粘膜撕裂、关节过度伸展和血肿。尽管其有害影响，但在温血马中发现了相对较高频率的 WFFS 携带者，这表明杂合子的优势。因此，在本研究中，我们的目标是：(1) 估计瑞典温血品种 (SWB) 中 WFFS 携带者的频率，(2) 估计 WFFS 携带者基因型对为不同学科培育的两个 SWB 亚群的性能特征的影响，(3) 模拟平衡选择和不同选择策略对载波频率的潜在影响。方法 总共对 1971 年至 2020 年间出生的 2288 匹 SWB 运动马进行了 WFFS 突变测试，并对 10 个传统评估性状和 50 个线性描述性状进行了估计育种值 (EBV)。结果 从 1971 年到 2020 年，从 2017 年出生的 511 匹随机选择的 SWB 马中计算出 WFFS 携带者的频率等于 7.4%，在整个测试的 SWB 马中的范围为 0.0% 至 12.0%。 WFFS 携带者基因型对于主要与运动和盛装舞步特征相关的几种 EBV 具有显着意义，尤其是对于不是为马术障碍训练的马匹。使用模拟，我们表明，平衡选择可以在 SWB 品种等种群中维持隐性致死等位基因，并且在没有平衡选择的情况下，频率预计会缓慢降低。最后，我们表明，对携带者公牛的选择可以导致突变等位基因的频率随着时间的推移而更快地降低。结论 需要进一步的研究来证实马的表现与 WFFS 携带者基因型之间的明显关联。对马性能特征的这种关联或新的致病突变的鉴定可以作为马育种的新工具，以选择健康、可持续和表现更好的马。我们表明，针对携带者公牛的选择可以导致突变等位基因的频率随着时间的推移而更快地降低。结论 需要进一步的研究来证实马的表现与 WFFS 携带者基因型之间的明显关联。对马性能特征的这种关联或新的致病突变的鉴定可以作为马育种的新工具，以选择健康、可持续和表现更好的马。我们表明，针对携带者公牛的选择可以导致突变等位基因的频率随着时间的推移而更快地降低。结论 需要进一步的研究来证实马的表现与 WFFS 携带者基因型之间的明显关联。对马性能特征的这种关联或新的致病突变的鉴定可以作为马育种的新工具，以选择健康、可持续和表现更好的马。