title: Concordance analysis for QTL detection in dairy cattle: a case study of leg morphology.
abstract: BACKGROUND
  The present availability of sequence data gives new opportunities to narrow down from QTL (quantitative trait locus) regions to causative mutations. Our objective was to decrease the number of candidate causative mutations in a QTL region. For this, a concordance analysis was applied for a leg conformation trait in dairy cattle. Several QTL were detected for which the QTL status (homozygous or heterozygous for the QTL) was inferred for each individual. Subsequently, the inferred QTL status was used in a concordance analysis to reduce the number of candidate mutations.
  
  
  METHODS
  Twenty QTL for rear leg set side view were mapped using Bayes C. Marker effects estimated during QTL mapping were used to infer the QTL status for each individual. Subsequently, polymorphisms present in the QTL regions were extracted from the whole-genome sequences of 71 Holstein bulls. Only polymorphisms for which the status was concordant with the QTL status were kept as candidate causative mutations.
  
  
  RESULTS
  QTL status could be inferred for 15 of the 20 QTL. The number of concordant polymorphisms differed between QTL and depended on the number of QTL statuses that could be inferred and the linkage disequilibrium in the QTL region. For some QTL, the concordance analysis was efficient and narrowed down to a limited number of candidate mutations located in one or two genes, while for other QTL a large number of genes contained concordant polymorphisms.
  
  
  CONCLUSIONS
  For regions for which the concordance analysis could be performed, we were able to reduce the number of candidate mutations. For part of the QTL, the concordant analyses narrowed QTL regions down to a limited number of genes, of which some are known for their role in limb or skeletal development in humans and mice. Mutations in these genes are good candidates for QTN (quantitative trait nucleotides) influencing rear leg set side view.
authors.affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, 78350 Jouy-en-Josas, France. irene.vanderberg@jouy.inra.fr.
authors.forename: Irene
authors.initials: I
authors.lastname: van den Berg
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fritz
authors.forename: Sabrina
authors.initials: S
authors.lastname: Rodriguez
authors.forename: Dominique
authors.initials: D
authors.lastname: Rocha
authors.forename: Mekki
authors.initials: M
authors.lastname: Boussaha
authors.forename: Mogens S
authors.initials: MS
authors.lastname: Lund
authors.forename: Didier
authors.initials: D
authors.lastname: Boichard
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D002417:Cattle / Q000033:anatomy & histology* / Q000235:genetics*; D002874:Chromosome Mapping / Q000662:veterinary; D005819:Genetic Markers; D006239:Haplotypes; D006579:Heterozygote; D015810:Linkage Disequilibrium; D035002:Lower Extremity / Q000033:anatomy & histology*; D008957:Models, Genetic; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci
chemical_list: D005819:Genetic Markers