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

Bernard Grisart ^* , Frédéric Farnir ^* , Latifa Karim ^*, Nadine Cambisano ^*, Jong-Joo Kim ^*, Alex Kvasz ^*, Myriam Mni ^*, Patricia Simon ^*, Jean-Marie Frère , Wouter Coppieters ^*, and Michel Georges ^* 

^*Department of Genetics, Faculty of Veterinary Medicine, University of Liège (B43), 20 Boulevard de Colonster, 4000 Liège (Sart Tilman), Belgium; and Centre for Protein Engineering, Institut de Chimie, University of Liège (B6), 3 Allée de la Chimie, B-4000 Liège (Sart Tilman), Belgium

Communicated by James E. Womack, Texas A&M University, College Station, TX, December 19, 2003 (received for review June 30, 2003)

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 V_max in producing triglycerides than the A allele.

B.G. and F.F. contributed equally to this work.

To whom correspondence should be addressed. E-mail: michel.georges{at}ulg.ac.be.

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