title: Genome-wide association study for calving performance using high-density genotypes in dairy and beef cattle.
abstract: BACKGROUND
  Calving difficulty and perinatal mortality are prevalent in modern-day cattle production systems. It is well-established that there is a genetic component to both traits, yet little is known about their underlying genomic architecture, particularly in beef breeds. Therefore, we performed a genome-wide association study using high-density genotypes to elucidate the genomic architecture of these traits and to identify regions of the bovine genome associated with them.
  
  
  RESULTS
  Genomic regions associated with calving difficulty (direct and maternal) and perinatal mortality were detected using two statistical approaches: (1) single-SNP (single nucleotide polymorphism) regression and (2) a Bayesian approach. Data included high-density genotypes on 770 Holstein-Friesian, 927 Charolais and 963 Limousin bulls. Several novel or previously identified genomic regions were detected but associations differed by breed. For example, two genomic associations, one each on chromosomes 18 and 2 explained 2.49 % and 3.13 % of the genetic variance in direct calving difficulty in the Holstein-Friesian and Charolais populations, respectively. Imputed Holstein-Friesian sequence data was used to refine the genomic regions responsible for significant associations. Several candidate genes on chromosome 18 were identified and four highly significant missense variants were detected within three of these genes (SIGLEC12, CTU1, and ZNF615). Nevertheless, only CTU1 contained a missense variant with a putative impact on direct calving difficulty based on SIFT (0.06) and Polyphen (0.95) scores. Using imputed sequence data, we refined a genomic region on chromosome 4 associated with maternal calving difficulty in the Holstein-Friesian population and found the strongest association with an intronic variant in the PCLO gene. A meta-analysis was performed across the three breeds for each calving performance trait to identify common variants associated with these traits in the three breeds. Our results suggest that a portion of the genetic variation in calving performance is common to all three breeds.
  
  
  CONCLUSIONS
  The genomic architecture of calving performance is complex and mainly influenced by many polymorphisms of small effect. We identified several associations of moderate effect size but the majority were breed-specific, indicating that breed-specific alleles exist for calving performance or that the linkage phase between genotyped allele and causal mutation varies between breeds.
authors.affiliation: Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland. Deirdre.purfield@teagasc.ie.|Animal & Grassland Research and Innovation Center, Teagasc, Moorepark, Fermoy, Co. Cork, Ireland. Deirdre.purfield@teagasc.ie.
authors.forename: Deirdre C
authors.initials: DC
authors.lastname: Purfield
authors.affiliation: Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland. dbradley@tcd.ie.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bradley
authors.affiliation: Irish Cattle Breeding Federation, Bandon, Co. Cork, Ireland. revans@icbf.com.
authors.forename: Ross D
authors.initials: RD
authors.lastname: Evans
authors.affiliation: Irish Cattle Breeding Federation, Bandon, Co. Cork, Ireland. fkearney@icbf.com.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Kearney
authors.affiliation: Animal & Grassland Research and Innovation Center, Teagasc, Moorepark, Fermoy, Co. Cork, Ireland. Donagh.Berry@teagasc.ie.
authors.forename: Donagh P
authors.initials: DP
authors.lastname: Berry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001499:Bayes Theorem; D002417:Cattle / Q000235:genetics* / Q000502:physiology; D003612:Dairying; D004420:Dystocia / Q000235:genetics / Q000662:veterinary*; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods / Q000662:veterinary*; D006801:Humans; D016014:Linear Models; D008297:Male; D054238:Perinatal Mortality; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D040641:Quantitative Trait Loci