title: Sequence-based Association Analysis Reveals an MGST1 eQTL with Pleiotropic Effects on Bovine Milk Composition.
abstract: The mammary gland is a prolific lipogenic organ, synthesising copious amounts of triglycerides for secretion into milk. The fat content of milk varies widely both between and within species, and recent independent genome-wide association studies have highlighted a milk fat percentage quantitative trait locus (QTL) of large effect on bovine chromosome 5. Although both EPS8 and MGST1 have been proposed to underlie these signals, the causative status of these genes has not been functionally confirmed. To investigate this QTL in detail, we report genome sequence-based imputation and association mapping in a population of 64,244 taurine cattle. This analysis reveals a cluster of 17 non-coding variants spanning MGST1 that are highly associated with milk fat percentage, and a range of other milk composition traits. Further, we exploit a high-depth mammary RNA sequence dataset to conduct expression QTL (eQTL) mapping in 375 lactating cows, revealing a strong MGST1 eQTL underpinning these effects. These data demonstrate the utility of DNA and RNA sequence-based association mapping, and implicate MGST1, a gene with no obvious mechanistic relationship to milk composition regulation, as causally involved in these processes.
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.|School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Mathew D
authors.initials: MD
authors.lastname: Littlejohn
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Tiplady
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Tania A
authors.initials: TA
authors.lastname: Fink
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lehnert
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lopdell
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Thomas
authors.initials: T
authors.lastname: Johnson
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Christine
authors.initials: C
authors.lastname: Couldrey
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Mike
authors.initials: M
authors.lastname: Keehan
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Sherlock
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Chad
authors.initials: C
authors.lastname: Harland
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Andrew
authors.initials: A
authors.lastname: Scott
authors.affiliation: School of Biological Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Snell
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Davis
authors.affiliation: Livestock Improvement Corporation, Hamilton, New Zealand.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Spelman
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D002417:Cattle; D002874:Chromosome Mapping / Q000662:veterinary; D033481:Chromosomes, Mammalian / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods* / Q000662:veterinary; D005982:Glutathione Transferase / Q000235:genetics*; D008892:Milk / Q000737:chemistry*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D017422:Sequence Analysis, DNA / Q000662:veterinary; D017423:Sequence Analysis, RNA / Q000662:veterinary
chemical_list: C122107:microsomal glutathione S-transferase-I; D005982:Glutathione Transferase