title: 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.
abstract: We recently mapped a quantitative trait locus (QTL) with a major effect on milk composition--particularly fat content--to the centromeric end of bovine chromosome 14. We subsequently exploited linkage disequilibrium to refine the map position of this QTL to a 3-cM chromosome interval bounded by microsatellite markers BULGE13 and BULGE09. We herein report the positional candidate cloning of this QTL, involving (1) the construction of a BAC contig spanning the corresponding marker interval, (2) the demonstration that a very strong candidate gene, acylCoA:diacylglycerol acyltransferase (DGAT1), maps to that contig, and (3) the identification of a nonconservative K232A substitution in the DGAT1 gene with a major effect on milk fat content and other milk characteristics.
authors.affiliation: Department of Genetics, Faculty of Veterinary Medicine, University of Liège (B43), 4000-Liège, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Grisart
authors.forename: Wouter
authors.initials: W
authors.lastname: Coppieters
authors.forename: Frédéric
authors.initials: F
authors.lastname: Farnir
authors.forename: Latifa
authors.initials: L
authors.lastname: Karim
authors.forename: Christine
authors.initials: C
authors.lastname: Ford
authors.forename: Paulette
authors.initials: P
authors.lastname: Berzi
authors.forename: Nadine
authors.initials: N
authors.lastname: Cambisano
authors.forename: Myriam
authors.initials: M
authors.lastname: Mni
authors.forename: Suzanne
authors.initials: S
authors.lastname: Reid
authors.forename: Patricia
authors.initials: P
authors.lastname: Simon
authors.forename: Richard
authors.initials: R
authors.lastname: Spelman
authors.forename: Michel
authors.initials: M
authors.lastname: Georges
authors.forename: Russell
authors.initials: R
authors.lastname: Snell
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000409:Alanine; D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002417:Cattle; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D003001:Cloning, Molecular / Q000379:methods; D020451:Contig Mapping / Q000662:veterinary; D051048:Diacylglycerol O-Acyltransferase; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D023061:Gene Order / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007774:Lactation; D008239:Lysine; D008297:Male; D051379:Mice; D008892:Milk / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism*; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D051381:Rats; D016415:Sequence Alignment / Q000662:veterinary
chemical_list: D005819:Genetic Markers; D000217:Acyltransferases; D051048:Diacylglycerol O-Acyltransferase; D008239:Lysine; D000409:Alanine