Abstract

ObjectiveAn initial RNA-Sequencing study revealed that UDP-galactose-4-epimerase (GALE) was one of the most promising candidates for milk protein concentration in Chinese Holstein cattle. This enzyme catalyzes the interconversion of UDP-galactose and UDP-glucose, an important step in galactose catabolism. To further validate the genetic effect of GALE on milk protein traits, genetic variations were identified, and genotypes-phenotypes associations were performed.MethodsThe entire coding region and the 5′-regulatory region (5′-UTR) of GALE were re-sequenced using pooled DNA of 17 unrelated sires. Association studies for five milk production traits were performed using a mixed linear animal model with a population encompassing 1,027 Chinese Holstein cows.ResultsA total of three variants in GALE were identified, including two novel variants (g.2114 A>G and g.2037 G>A) in the 5′-UTR and one previously reported variant (g.3836 G>C) in an intron. All three single nucleotide polymorphisms (SNPs) were associated with milk yield (p<0.0001), fat yield (p = 0.0006 to <0.0001), protein yield (p = 0.0232 to <0.0001) and protein percentage (p<0.0001), while no significant associations were detected between the SNPs and fat percentage. A strong linkage disequilibrium (D’ = 0.96 to 1.00) was observed among all three SNPs, and a 5 Kb haplotype block involving three main haplotypes with GAG, AGC, and AGG was formed. The results of haplotype association analyses were consistent with the results of single locus association analysis (p<0.0001). The phenotypic variance ratio above 3.00% was observed for milk protein yield that was explained by SNP-g.3836G >C.ConclusionOverall, our findings provided new insights into the polymorphic variations in bovine GALE gene and their associations with milk protein concentration. The data indicate their potential uses for marker-assisted breeding or genetic selection schemes.

Highlights

  • Milk proteins are important nutrients and milk protein concentration serves as valuable index for milk quality

  • Strong interactions were observed between GALE and several other genes such as lactalbumin, alpha (LALBA), beta 1,4galactosyltransferase, polypeptide 1 (B4GALT1), and UDPglucose 6-dehydrogenase (UGDH) that play important roles in milk composition synthesis (Supplementary Figure S1) [8,9,10]

  • Genetic sampling A total of 1,027 Chinese Holstein cows and their 17 corresponding sires were considered as the study population

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Summary

Introduction

Milk proteins are important nutrients and milk protein concentration serves as valuable index for milk quality. With the development of genomics, bioinformatics and statistical genetics, a single gene or chromosome segments affecting important economic traits can be analyzed [2]. It is possible to improve milk protein concentration through marker assisted selection (MAS) or genomic selection schemes, the challenge, is to identify key genes or causal variations affecting milk protein traits [3,4,5,6]. Based on the biological function and trans­ criptional effects on milk protein traits, the current study mined to screen the full-length coding regions of the GALE gene for single nucleotide polymorphisms (SNPs) and to evaluate the genetic effects of polymorphisms on milk production traits in a large Chinese Holstein population

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