Disease relevance of DGAT1

• By using a baculovirus expression system, we have expressed both DGAT1 alleles in Sf9 cells and show that the K allele, causing an increase in milk fat percentage in the live animal, is characterized by a higher Vmax in producing triglycerides than the A allele [1].
• However, neither of the two polymorphisms of candidate genes tested, DGAT1 nor TG, showed a significant (P > 0.10) association with the backfat EBV in the cattle populations examined [2].

High impact information on DGAT1

• We recently used a positional cloning approach to identify a nonconservative lysine to alanine substitution (K232A) in the bovine DGAT1 gene that was proposed to be the causative quantitative trait nucleotide underlying a quantitative trait locus (QTL) affecting milk fat composition, previously mapped to the centromeric end of bovine chromosome 14 [1].
• We have constructed a high-density single-nucleotide polymorphism map of the 3.8-centimorgan BULGE30-BULGE9 interval containing the QTL and show that the association with milk fat percentage maximizes at the DGAT1 gene [1].
• Our mapping studies placed DGAT1 close to the region of a quantitative trait locus (QTL) on bovine chromosome 14 for variation in fat content of milk [3].
• It became a functional candidate gene for lactation traits after studies indicated that mice lacking both copies of DGAT1 are completely devoid of milk secretion, most likely because of deficient triglyceride synthesis in the mammary gland [3].
• DGAT1 encodes diacylglycerol O-acyltransferase (EC ), a microsomal enzyme that catalyzes the final step of triglyceride synthesis [3].

Biological context of DGAT1

• Due to the presence of a potential transcription factor binding site in the 18mer element of the VNTR, the variation in the number of tandem repeats of the 18mer element might be causal for the variability in the transcription level of the DGAT1 gene [4].
• Positional candidate cloning of a QTL in dairy cattle: identification of a missense mutation in the bovine DGAT1 gene with major effect on milk yield and composition [5].
• These will form the basis of future linkage disequilibrium studies to test whether any genes neighboring DGAT1 are associated with variation in milk fat percentage, thereby testing the candidate status of DGAT1 [6].
• This study investigated whether the diallelic DGAT1 polymorphism is responsible for all the genetic variation at the centromeric region of this chromosome for milk, fat, and protein yield and fat and protein percentage [7].
• A restriction fragment length polymorphism assay was applied to diagnose the K232A substitution in DGAT1 [8].

Anatomical context of DGAT1

• The activity of DGAT was generally higher from SC adipose tissue than from IM adipose or muscle tissue [9].
• These results suggest that the activation of DGAT by spermine may reside in its ability to preserve the membrane integrity of microsomal membranes, to maintain the optimal and noninhibitory levels of palmitoyl-CoA and to provide a cationic environment required for the optimal activity of this enzyme [10].

Associations of DGAT1 with chemical compounds

• Association of a lysine-232/alanine polymorphism in a bovine gene encoding acyl-CoA:diacylglycerol acyltransferase (DGAT1) with variation at a quantitative trait locus for milk fat content [3].
• Ad libitum feeding upregulated a number of genes associated with liver triacylglycerol synthesis (DGAT1) and proinflammatory cytokines (TNFAIP3) [11].
• A specific allele of the DGAT1 promoter VNTR showed significant effects on the traits lactose yield and content, milk energy content, and SCS compared with the other alleles [12].
• Our objective was to estimate the frequency of the DGAT1 K232A polymorphism in the main Zebu and Taurine breeds in Brazil as well as in Zebu x Taurine crossbreds as a potential QTL for marker-assisted selection [13].
• The activation of DGAT, either by spermine or Mg2+ was reversed in the presence of ATP [10].

Other interactions of DGAT1

• Whereas DGAT1, GHR, and CSN1S1 polymorphisms showed association with some traits in individual populations, the lack of consistent predictive merit between populations indicates they may not be suited for beef cattle selection [14].
• To elucidate these QTL effects, animals from a German Holstein granddaughter design (18 families, 1,291 sons) were genotyped for CYP11B1 (V30A) and DGAT1 (K232A) polymorphisms [15].
• In this study, the frequencies and the effects of alleles at the DGAT1 K232A and at the DGAT1 promoter variable number of tandem repeat (VNTR) locus on BTA14, and of alleles at the CSN1S1 (alpha(S1)-casein-encoding gene) promoter on BTA6 in the German Angeln dairy cattle population were investigated [12].
• The associations between the combined genotypes DGAT1/LTF and DGAT1/LEPTIN analyzed traits are presented as examples.The microarray based on APEX (Arrayed Primer Extension) is a fast and reliable method for multiple SNP analysis of potential application in marker-assisted selection [16].

References