title: Molecular characterization of a long range haplotype affecting protein yield and mastitis susceptibility in Norwegian Red cattle.
abstract: BACKGROUND
  Previous fine mapping studies in Norwegian Red cattle (NRC) in the region 86-90.4 Mb on Bos taurus chromosome 6 (BTA6) has revealed a quantitative trait locus (QTL) for protein yield (PY) around 88 Mb and a QTL for clinical mastitis (CM) around 90 Mb. The close proximity of these QTLs may partly explain the unfavorable genetic correlation between these two traits in NRC. A long range haplotype covering this region was introduced into the NRC population through the importation of a Holstein-Friesian bull (1606 Frasse) from Sweden in the 1970s. It has been suggested that this haplotype has a favorable effect on milk protein content but an unfavorable effect on mastitis susceptibility. Selective breeding for milk production traits is likely to have increased the frequency of this haplotype in the NRC population.
  
  
  RESULTS
  Association mapping for PY and CM in NRC was performed using genotypes from 556 SNPs throughout the region 86-97 Mb on BTA6 and daughter-yield-deviations (DYDs) from 2601 bulls made available from the Norwegian dairy herd recording system. Highest test scores for PY were found for single-nucleotide polymorphisms (SNPs) within and surrounding the genes CSN2 and CSN1S2, coding for the β-casein and α(S2)-casein proteins. High coverage re-sequencing by high throughput sequencing technology enabled molecular characterization of a long range haplotype from 1606 Frasse encompassing these two genes. Haplotype analysis of a large number of descendants from this bull indicated that the haplotype was not markedly disrupted by recombination in this region. The haplotype was associated with both increased milk protein content and increased susceptibility to mastitis, which might explain parts of the observed genetic correlation between PY and CM in NRC. Plausible causal polymorphisms affecting PY were detected in the promoter region and in the 5'-flanking UTR of CSN1S2. These polymorphisms could affect transcription or translation of CSN1S2 and thereby affect the amount of α(S2)-casein in milk. Highest test scores for CM were found in the region 89-91 Mb on BTA6, very close to a cluster of genes coding for CXC chemokines. Expression levels of some of these CXC chemokines have previously been shown to increase in bovine mammary gland cell lines after exposure to bacterial cell wall components.
  
  
  CONCLUSIONS
  Molecular characterization of the long range haplotype from the Holstein-Friesian bull 1606 Frasse, imported into NRC in the 1970s, revealed polymorphisms that could affect transcription or translation of the casein gene CSN1S2. Sires with this haplotype had daughters with significantly elevated milk protein content and selection for milk production traits is likely to have increased the frequency of this haplotype in the NRC population. The haplotype was also associated with increased mastitis susceptibility, which might explain parts of the genetic correlation between PY and CM in NRC.
authors.affiliation: Centre for Integrative Genetics, Department of Animal and Aquacultural Sciences, Norwegian University of Life Sciences, N-1432 Aas, Norway. marte.sodeland@umb.no
authors.forename: Marte
authors.initials: M
authors.lastname: Sodeland
authors.forename: Harald
authors.initials: H
authors.lastname: Grove
authors.forename: Matthew
authors.initials: M
authors.lastname: Kent
authors.forename: Simon
authors.initials: S
authors.lastname: Taylor
authors.forename: Morten
authors.initials: M
authors.lastname: Svendsen
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Hayes
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Lien
mesh_terms: D000818:Animals; D002364:Caseins / Q000235:genetics; D002417:Cattle; D002874:Chromosome Mapping; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D008297:Male; D008414:Mastitis, Bovine / Q000235:genetics*; D008894:Milk Proteins / Q000032:analysis; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: D002364:Caseins; D008894:Milk Proteins