[en] 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.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Grisart, Bernard; Université de Liège - ULiège > Département de productions animales > Génomique animale
Farnir, Frédéric ; Université de Liège - ULiège > Département de productions animales > Biostatistique, économie, sélection animale
Karim, Latifa ; Université de Liège - ULiège > Département de productions animales > Génomique animale
Cambisano, Nadine ; Université de Liège - ULiège > Département de productions animales > Génomique animale
Kim, Jong-Joo; Université de Liège - ULiège > Département de productions animales > Génomique animale
Kvasz, Alex; Université de Liège - ULiège > Département de productions animales > Génomique animale
Mni, Myriam ; Université de Liège - ULiège > Département de productions animales > Génomique animale
Heyen, D. W., Weller, J. I., Ron, M., Band, M., Beever, J. E., Feldmesser, E., Da, Y., Wiggans, G. R., VanRaden, P. M. & Lewin, H. A. (1999) Physiol. Genomics 1, 165-175.
Riquet, J., Coppieters, W., Cambisano, N., Arranz, J.-J., Berzi, P., Davis, S., Grisart, B., Farnir, F., Karim, L., Mni, M., et al. (1999) Proc. Natl. Acad. Sci. USA 96, 9252-9257.
Farnir, F., Grisart, B., Coppieters, W., Riquet, J., Berzi, P., Cambisano, N., Karim, L., Mni, M., Simon, P., Wagenaar, D. & Georges, M. (2002) Genetics 161, 275-287.
Grisart, B., Coppieters, W., Farnir, F., Karim, L., Ford, C., Cambisano, N., Mni, M., Reid, S., Spelman, R., Georges, M. & Snell, R. (2002) Genome Res. 12, 222-231.
Cases, S., Smith, S. J., Zheng, Y. W., Myers, H. M., Lear, S. R., Sande, E., Novak, S., Collins, C., Welch, C. B., Lusis, A. J., et al. (1998) Proc. Natl. Acad. Sci. USA 95, 13018-13023.
Smith, S. J., Cases, S., Jensen, D. R., Chen, H. C., Sande, E., Tow, B., Sanan, D. A., Raber, J., Eckel, R. H. & Farese, R. V., Jr. (2000) Nat. Genet. 25, 87-90.
Winter, A., Kramer, W., Werner, F. A., Kollers, S., Kata, S., Durstewitz, G., Buitkamp, J., Womack, J. E., Thaller, G. & Fries, R. (2002) Proc. Natl. Acad. Sci. USA 99, 9300-9305.
Spelman, R. J., Ford, C. A., McElhinney, P., Gregory, G. C. & Snell, R. G. (2002) J. Dairy Sci. 85, 3514-3517.
Karim, L., Coppieters, W., Grobet, L., Valentini, A. & Georges, M. (2000) Anim. Genet. 31, 396-399.
Farnir, F., Coppieters, W., Arranz, J. J., Berzi, P., Cambisano, N., Grisart, B., Karim, L., Marcq, F., Moreau, L., Mni, M., et al. (2000) Genome Res. 10, 220-227.
Lynch, M. & Walsh, B. (1997) Genetics and Analysis of Quantitative Traits (Sinauer, Sunderland, MA).
Johnson, D. L. & Thompson, R. (1995) J. Dairy Sci. 78, 449-456.
Sabeti, P. C., Reich, D. E., Higgins, J. M., Levine, H. Z., Richter, D. J., Schaffner, S. F., Gabriel, S. B., Platko, J. V., Patterson, N. J., McDonald, G. J., et al. (2002) Nature 419, 832-837.
Looft, C., Reinsch, N., Karall-Albrecht, C., Paul, S., Brink, M., Thomsen, H., Brockmann, G., Kuhn, C., Schwerin, M. & Kalm, E. (2001) Mamm. Genome 12, 646-650.
Lander, E. & Green, P. (1987) Proc. Natl. Acad. Sci. USA 84, 2363-2367.
Glazier, A. M., Nadeau, J. H. & Aitman, T. J. (2002) Science 298, 2345-2349.
Cheng, D., Meegalla, R. L., He, B., Cromley, D. A., Billheimer, J. T. & Young, P. R. (2001) Biochem. J. 359, 707-714.
Kim, J. J. & Georges, M. (2002) Asian-Aust. J. Anim. Sci. 15, 1250-1256.
Van Laere, A. S., Nguyen, M., Braunschweig, M., Nezer, C., Collette, C., Moreau, L., Archibald, A., Haley, C., Buys, N., Andersson, G., et al. (2003) Nature 425, 832-836.