Genetic and functional confirmation of the causality of the DGAT1 K232A quantitative trait nucleotide in affecting milk yield and composition

Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2398-403. doi: 10.1073/pnas.0308518100.

Abstract

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. We herein generate genetic and functional data that confirm the causality of the DGAT1 K232A mutation. 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. We provide evidence that the K allele has undergone a selective sweep. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics*
  • Acyltransferases / metabolism
  • Amino Acid Substitution
  • Animals
  • Base Sequence
  • Cattle / genetics*
  • Cell Line
  • Chromosome Mapping
  • DNA Primers
  • Diacylglycerol O-Acyltransferase
  • Female
  • Genetic Markers
  • Lactation
  • Linkage Disequilibrium
  • Male
  • Mammary Glands, Animal
  • Milk / metabolism*
  • Mutagenesis, Site-Directed
  • Quantitative Trait Loci
  • Recombinant Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spodoptera

Substances

  • DNA Primers
  • Genetic Markers
  • Recombinant Proteins
  • Acyltransferases
  • Diacylglycerol O-Acyltransferase