A 660-Kb deletion with antagonistic effects on fertility and milk production segregates at high frequency in Nordic Red cattle: additional evidence for the common occurrence of balancing selection in livestock.
A 660-Kb deletion with antagonistic effects on fertility and milk production segregates at high frequency in Nordic Red cattle: additional evidence for the common occurrence of balancing selection in livestock.
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DOI：
10.1371/journal.pgen.1004049
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发表时间：
2014-01
期刊：
影响因子：
4.5
通讯作者：
Druet T
中科院分区：
文献类型：
--
作者：
Kadri NK;Sahana G;Charlier C;Iso-Touru T;Guldbrandtsen B;Karim L;Nielsen US;Panitz F;Aamand GP;Schulman N;Georges M;Vilkki J;Lund MS;Druet T
在奶牛中，人工授精的广泛使用导致了选择强度的增加，这导致了生产力的显著提高。然而，奶牛的生育能力也随之严重下降。一般认为，这种减少主要是由于高产奶牛在泌乳高峰期的负能量平衡。我们在此描述了北欧红牛的一个主要生育力QTL的精细定位，并确定了一个660 kb的缺失，包括四个基因作为致病变异。我们表明，删除是一个隐性胚胎致死突变。这可能是由于RNASEH2B的丢失造成的，已知RNASEH2B会导致小鼠胚胎死亡。尽管它对生育力有显著影响，但丹麦、瑞典和芬兰红牛中分别有13%、23%和32%的动物携带该缺失。为了解释这一点，我们寻找对其他性状的有利影响，发现缺失对产奶量有很强的积极影响。这项研究表明，胚胎致死突变在家牛生育力下降中占有不可忽视的部分，而对产奶量的相关积极影响可能是负遗传相关性的一部分。我们的研究增加了结构变异有助于动物表型变异的证据，并且平衡选择在牲畜物种中可能比以前认识到的更常见。我们报告了一个大的缺失，包括四个基因的鉴定和证明其对北欧红牛生育力的负面影响。我们表明，这种缺失是reckarylethal（纯合子胚胎死亡），因此，当携带者母牛交配携带者公牛，有一个高风险的胚胎死亡率。因此，这种交配的授精失败的机会更高。令人惊讶的是，尽管其负面影响，删除是频繁的北欧红牛。我们表明，这种高频率可能是一个事实，即删除与牛奶产量增加，因此选择的结果。由于人工授精的广泛使用导致近亲繁殖水平的增加，这种隐性致死等位基因可能是在牛中观察到的生育力降低的不可忽略的部分。
In dairy cattle, the widespread use of artificial insemination has resulted in increased selection intensity, which has led to spectacular increase in productivity. However, cow fertility has concomitantly severely declined. It is generally assumed that this reduction is primarily due to the negative energy balance of high-producing cows at the peak of lactation. We herein describe the fine-mapping of a major fertility QTL in Nordic Red cattle, and identify a 660-kb deletion encompassing four genes as the causative variant. We show that the deletion is a recessive embryonically lethal mutation. This probably results from the loss of RNASEH2B, which is known to cause embryonic death in mice. Despite its dramatic effect on fertility, 13%, 23% and 32% of the animals carry the deletion in Danish, Swedish and Finnish Red Cattle, respectively. To explain this, we searched for favorable effects on other traits and found that the deletion has strong positive effects on milk yield. This study demonstrates that embryonic lethal mutations account for a non-negligible fraction of the decline in fertility of domestic cattle, and that associated positive effects on milk yield may account for part of the negative genetic correlation. Our study adds to the evidence that structural variants contribute to animal phenotypic variation, and that balancing selection might be more common in livestock species than previously appreciated. We report the identification of a large deletion encompassing four genes and the demonstration of its negative effect on fertility in Nordic Red dairy cattle. We show that this deletion is recessively lethal (homozygous embryos die) and therefore, when carrier cows are mated to carrier bulls, there is a high risk of embryonic mortality. As a result, chances of insemination failure are higher for such matings. Surprisingly, despite its negative effect, the deletion is frequent in Nordic Red cattle. We show that this high frequency may be a consequence of the fact that the deletion is associated with increased milk production and therefore selected for. Due to increased levels of inbreeding resulting from the widespread use of artificial insemination, such recessive lethal alleles may account for a non-negligible fraction of the reduction in fertility observed in cattle.
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DOI：
10.1126/science.1215040
发表时间：
2012-02-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
MacArthur DG;Balasubramanian S;Frankish A;Huang N;Morris J;Walter K;Jostins L;Habegger L;Pickrell JK;Montgomery SB;Albers CA;Zhang ZD;Conrad DF;Lunter G;Zheng H;Ayub Q;DePristo MA;Banks E;Hu M;Handsaker RE;Rosenfeld JA;Fromer M;Jin M;Mu XJ;Khurana E;Ye K;Kay M;Saunders GI;Suner MM;Hunt T;Barnes IH;Amid C;Carvalho-Silva DR;Bignell AH;Snow C;Yngvadottir B;Bumpstead S;Cooper DN;Xue Y;Romero IG;1000 Genomes Project Consortium;Wang J;Li Y;Gibbs RA;McCarroll SA;Dermitzakis ET;Pritchard JK;Barrett JC;Harrow J;Hurles ME;Gerstein MB;Tyler-Smith C
通讯作者：
Tyler-Smith C
从DNA中酶促去除核糖核苷酸对于哺乳动物的基因组完整性和发育至关重要。
影响因子：
64.5
作者：
Reijns MA;Rabe B;Rigby RE;Mill P;Astell KR;Lettice LA;Boyle S;Leitch A;Keighren M;Kilanowski F;Devenney PS;Sexton D;Grimes G;Holt IJ;Hill RE;Taylor MS;Lawson KA;Dorin JR;Jackson AP
通讯作者：
Jackson AP
影响因子：
7
作者：
Li, Heng;Ruan, Jue;Durbin, Richard
通讯作者：
Durbin, Richard
影响因子：
56.9
作者：
FUJII, J;OTSU, K;MACLENNAN, DH
通讯作者：
MACLENNAN, DH
影响因子：
2.4
作者：
Beever, JE;Smit, MA;Cockett, NE
通讯作者：
Cockett, NE