Variants in the 3′ untranslated region of the ovine acetyl-coenzyme A acyltransferase 2 gene are associated with dairy traits and exhibit differential allelic expression

Abstract

The acetyl-CoA acyltransferase 2 (ACAA2) gene encodes an enzyme of the thiolase family that is involved in mitochondrial fatty acid elongation and degradation by catalyzing the last step of the respective β-oxidation pathway. The increased energy needs for gluconeogenesis and triglyceride synthesis during lactation are met primarily by increased fatty acid oxidation. Therefore, the ACAA2 enzyme plays an important role in the supply of energy and carbon substrates for lactation and may thus affect milk production traits. This study investigated the association of the ACAA2 gene with important sheep traits and the putative functional involvement of this gene in dairy traits. A single nucleotide substitution, a T to C transition located in the 3' untranslated region of the ACAA2 gene, was used in mixed model association analysis with milk yield, milk protein yield and percentage, milk fat yield and percentage, and litter size at birth. The single nucleotide polymorphism was significantly associated with total lactation production and milk protein percentage, with respective additive effects of 6.81 ± 2.95 kg and -0.05 ± 0.02%. Additionally, a significant dominance effect of 0.46 ± 0.21 kg was detected for milk fat yield. Homozygous TT and heterozygous CT animals exhibited higher milk yield compared with homozygous CC animals, whereas the latter exhibited increased milk protein percentage. Expression analysis from age-, lactation-, and parity-matched female sheep showed that mRNA expression of the ACAA2 gene from TT animals was 2.8- and 11.8-fold higher in liver and mammary gland, respectively. In addition, by developing an allelic expression imbalance assay, it was estimated that the T allele was expressed at an average of 18% more compared with the C allele in the udder of randomly selected ewes. We demonstrated for the first time that the variants in the 3' untranslated region of the ovine ACAA2 gene are differentially expressed in homozygous ewes of each allele and exhibit allelic expression imbalance within heterozygotes in a tissue-specific manner, supporting the existence of cis-regulatory DNA variation in the ovine ACAA2 gene. This is the first study reporting differential allelic imbalance expression of a candidate gene associated with milk production traits in dairy sheep.

ACAA2 and FASN polymorphisms affect the fatty acid profile of Chios sheep milk

“…In the present work, informative polymorphisms were only observed for the ACAA2 and FASN genes (Tables 1 and 2). Allelic frequencies in the ACAA2 SNP locus were 0.47 and 0.53 for the C and T alleles, respectively, similarly to Orford et al (2012) and Miltiadou et al (2017a), while genotypic frequencies were found to deviate from Hardy-Weinberg equilibrium (online Supplementary Table S3), consistently with our latest study where the frequency of the genotypes carrying the T allele was higher probably due to directional animal selection for increased milk yield (Miltiadou et al, 2017a). In the FASN SNP locus, the respective frequencies for the C and T alleles were 0.67 and 0.33 (online Supplementary Table S3), whereas the C allele frequency reported for the Altamurana and Gentile di Puglia breeds was 0.93 and 1 in Sarda breed (Crisà et al, 2010), suggesting important inter-breed differences.…”

“…Therefore, the SNP previously associated with milk yield (Orford et al, 2012;Miltiadou et al, 2017a), protein content and fat yield in Chios sheep (Miltiadou et al, 2017a) is also correlated with ω6/ω3 content, an index associated with human health benefits. Similarly to Miltiadou et al (2017a), fat percentage was not affected by the identified ACAA2 polymorphism.…”

Detection of a 4 bp Mutation in the 3′UTR Region of Goat Sox9 Gene and Its Effect on the Growth Traits

“…Several previous studies have shown that 3 UTR variants can affect gene transcription [49,50], and structural changes in the 3 UTR region are closely related to livestock and poultry production performance [51][52][53]. The 3 UTR is generally thought to regulate gene expression by affecting the stability of mRNA.…”

Proteomics Analysis and Identification of Critical Proteins and Network Interactions That Regulate the Specific Deposition of IMF of Jingyuan Chicken

“…Further analysis found that among the 21 proteins quanti ed, ten proteins that regulate fat deposition have major variations in expression between leg muscles and breast muscles. For example, Acetyl CoA Acyltransferase 2 (AcetylCoAacyltransferase 2, ACAA2) is a key enzyme for fatty acid oxidation, widely distributed in mammalian and bird tissues and cytoplasm, and plays a vital role in the metabolism of fatty acids (Sodhi et al 2014), and regulates intermuscular fat content (Miltiadou et al 2017). Hence, this gene is considered a candidate for detecting intermuscular fat content (Miltiadou et al 2017).…”