Variants in the 3'UTR of the ovine Acetyl-Coenzyme A Acyltranferase 2 gene are associated with dairy traits and exhibit differential allelic expression

D Miltiadou, AL Hager-Theodorides, S Symeou, C Constantinou, A Psifidi, G Banos, O Tzamaloukas

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)
1 Downloads (Pure)

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
Original languageEnglish
Pages (from-to)6285 - 6297
Number of pages13
JournalJournal of Dairy Science
Volume100
Issue number8
Early online date16 Jun 2017
DOIs
Publication statusFirst published - 16 Jun 2017

Fingerprint

acetyl coenzyme A
acyltransferases
3' untranslated regions
dairies
sheep
milk protein percentage
lactation
genes
milk fat yield
alleles
milk yield
ewes
milk production
animals
dairy sheep
milk fat percentage
beta oxidation
milk protein yield
gluconeogenesis
energy

Bibliographical note

1030786

Keywords

  • 3'UTR Cis-acting SNP
  • ACAA2 association
  • Dairy sheep
  • Gene expression

Cite this

Miltiadou, D ; Hager-Theodorides, AL ; Symeou, S ; Constantinou, C ; Psifidi, A ; Banos, G ; Tzamaloukas, O. / Variants in the 3'UTR of the ovine Acetyl-Coenzyme A Acyltranferase 2 gene are associated with dairy traits and exhibit differential allelic expression. In: Journal of Dairy Science. 2017 ; Vol. 100, No. 8. pp. 6285 - 6297.
@article{e94f3e9892484d128aa74eaccc28b382,
title = "Variants in the 3'UTR of the ovine Acetyl-Coenzyme A Acyltranferase 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",
keywords = "3'UTR Cis-acting SNP, ACAA2 association, Dairy sheep, Gene expression",
author = "D Miltiadou and AL Hager-Theodorides and S Symeou and C Constantinou and A Psifidi and G Banos and O Tzamaloukas",
note = "1030786",
year = "2017",
month = "6",
day = "16",
doi = "10.3168/jds.2016-12326",
language = "English",
volume = "100",
pages = "6285 -- 6297",
journal = "Journal of Dairy Science",
issn = "0022-0302",
publisher = "American Dairy Science Association",
number = "8",

}

Variants in the 3'UTR of the ovine Acetyl-Coenzyme A Acyltranferase 2 gene are associated with dairy traits and exhibit differential allelic expression. / Miltiadou, D; Hager-Theodorides, AL; Symeou, S; Constantinou, C; Psifidi, A; Banos, G; Tzamaloukas, O.

In: Journal of Dairy Science, Vol. 100, No. 8, 16.06.2017, p. 6285 - 6297.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Variants in the 3'UTR of the ovine Acetyl-Coenzyme A Acyltranferase 2 gene are associated with dairy traits and exhibit differential allelic expression

AU - Miltiadou, D

AU - Hager-Theodorides, AL

AU - Symeou, S

AU - Constantinou, C

AU - Psifidi, A

AU - Banos, G

AU - Tzamaloukas, O

N1 - 1030786

PY - 2017/6/16

Y1 - 2017/6/16

N2 - 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

AB - 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

KW - 3'UTR Cis-acting SNP

KW - ACAA2 association

KW - Dairy sheep

KW - Gene expression

U2 - 10.3168/jds.2016-12326

DO - 10.3168/jds.2016-12326

M3 - Article

VL - 100

SP - 6285

EP - 6297

JO - Journal of Dairy Science

JF - Journal of Dairy Science

SN - 0022-0302

IS - 8

ER -