A post-GWAS replication study confirming the association of C1<?Pub Caret?>4H8orf33 gene with milk production traits in dairy cattle

Abstract

Genome-wide association studies with an Illumina Bovine50K chip have detected 105 SNPs associated with one or multiple milk production traits in the Chinese Holstein population. Of these, 38 significant SNPs detected with high confidence by both L1-TDT and MMRA methods were selected to further mine potential key genes affecting milk yield and milk composition. By blasting the flanking sequences of these 38 SNPs with the bovine genome sequence combined with comparative genomics analysis, 26 genes were found to contain or be near to such SNPs. Among them, the C14H8orf33 gene is merely 87 bp away from the significant SNP, Hapmap30383-BTC-005848. Hence, we report herein genotype-phenotype associations to further validate the genetic effects of the C14H8orf33 gene. By pooled DNA sequencing of 14 unrelated Holstein sires, a total of 18 with seven novel SNPs were identified. Among them, nine SNPs were in the 5′ regulatory region, one in exon 6 and the other in the 3′ UTR and 3′ regulatory region. A total of nine of these identified SNPs were successfully genotyped and analyzed by mass spectrometry for association with five milk production traits in an independent resource population. The results showed that these SNPs were statistically significant for more than two traits [P<(0.0001-0.0267)]. In addition, mRNA expression analyses revealed that C14H8orf33 was ubiquitous in eight different tissues, with a relatively higher expression level in the mammary gland than in other tissues. These findings, therefore, provide strong evidence for association of C14H8orf33 variants with milk yield and milk composition traits and may be applied in Chinese Holstein breeding programs.

Keywords

GWAS / functional annotation / Chinese Holstein / milk production traits / C14H8orf33 gene / single nucleotide polymorphisms / association study

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Acknowledgements

This work was supported by the National High-tech R&D Program of China (2013AA102504), the National Key Technology R&D Program (2011BAD28B02), the National Transgenic Major Project (2014ZX08009-053B), the Beijing Innovation Team of Technology System in the National Dairy Industry, the Beijing Research and Technology Program (D121100003312001), the earmarked fund for Modern Agro-industry Technology Research System (CARS-37) and the Program for Changjiang Scholar and Innovation Research Team in University (IRT1191). The authors also express appreciation for the kind help from the official Dairy Data Center of China in providing the official EBVs data.

Supplementary materialƒThe online version of this article at http://dx.doi.org/(doi: 10.15302/J-FASE-2014037) contains supplementary material (Appendix A).

Compliance with ethics guidelinesƒShaohua Yang, Chao Qi, Yan Xie, Xiaogang Cui, Yahui Gao, Jianping Jiang, Li Jiang, Shengli Zhang, Qin Zhang and Dongxiao Sun declare that they have no conflict of interest or financial conflicts to disclose.ƒAll applicable institutional and national guidelines for the care and use of animals were followed.

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Higher Education Press and Springer-Verlag Berlin Heidelberg