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

PLoS Genet. 2014 Jan;10(1):e1004049. doi: 10.1371/journal.pgen.1004049. Epub 2014 Jan 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breeding
  • Cattle
  • Dairy Products
  • Energy Metabolism / genetics
  • Female
  • Fertility / genetics*
  • Genes, Lethal / genetics
  • Lactation / genetics
  • Livestock
  • Mice
  • Milk Proteins / genetics
  • Milk*
  • Selection, Genetic*
  • Sequence Deletion / genetics*

Substances

  • Milk Proteins

Grants and funding

This work was performed in the projects ‘Genomic Selection – from function to efficient utilization in cattle breeding’ (grant no. 3412-08-02253), funded by the Danish Directorate for Food, Fisheries and Agri Business, VikingGenetics, Nordic Cattle Genetic Evaluation, and Aarhus University. The sequencing of Finnish Ayrshire bulls were done in the “Quantomics” project funded by EC (FP7/2007-2013, agreement no. 222664). TD and CC are funded by the Walloon Direction Générale Opérationnelle Agriculture, Ressources naturelles et Environnement ‘DGARNE’ (grants D31-1271 and D31-1272). MG is funded by the European Research Council (ERC-DAMONA) and by the Walloon DGARNE. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.