title: Variants in the 3' UTR of general Transcription factor IIF, polypeptide 2 affect female calving efficiency in Japanese Black cattle.
abstract: BACKGROUND
  Calving efficiency can be described as the measure of a cow's ability to produce viable offspring within a specific period of time. This trait is crucial in beef cattle because calves are necessary both for the production of beef and for heifer replacements. Recently, the number of calves produced at 4 years of age (NCP4) has been used to evaluate the calving efficiency of Japanese Black cattle. To identify variants associated with calving efficiency in Japanese Black cattle, we conducted a genome-wide association study (GWAS) using 688 animals with extreme NCP4 values selected from 15,225 animals.
  
  
  RESULTS
  We identified genetic variants on bovine chromosome 12 (BTA12) that were associated with NCP4. The General Transcription Factor IIF, polypeptide 2 (GTF2F2), located in the 132 kbp-associated region, proved to be in strong linkage disequilibrium. We found 15 associated variants in the promoter and the 3' UTR regions. Consistent with this finding, transcripts of GTF2F2 derived from the haplotype (Q) with the increased number of calves were 1.33-fold more abundant than q-derived transcripts. Furthermore, luciferase assays revealed that the activity of the 3' UTR, a region that includes nine SNPs, was higher in constructs with the Q haplotype than in those with the q haplotype by approximately 1.35-fold. In contrast, the activity of the promoter region did not differ between haplotypes. The association was replicated in an independent sample of 827 animals that were randomly selected from the remainder of the cohort from the same farms used in the GWAS. In the replicated population, the frequency of the Q haplotype is 0.313, and this haplotype accounts for 2.69% of the total phenotypic variance. The effect of the Q to q haplotype substitution on NCP4 was 0.054 calves. These findings suggest that variants in the 3' UTR of GTF2F2 affect the level of GTF2F2 mRNA, which is associated with calving efficiency.
  
  
  CONCLUSIONS
  This GWAS has identified variants in the 3' UTR of GTF2F2 that were associated with the NCP4 of Japanese Black cattle, and this association was validated in an independent sample. The Q haplotype will be immediately useful in improving the calving efficiency of Japanese Black cattle.
authors.affiliation: Shirakawa Institute of Animal Genetics, Japan Livestock Technology Association, Odakura, Nishigo, Fukushima 961-8061, Japan. sasakis@siag.or.jp
authors.forename: Shinji
authors.initials: S
authors.lastname: Sasaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ibi
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Tamako
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Shogo
authors.initials: S
authors.lastname: Ikeda
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
mesh_terms: D020413:3' Untranslated Regions; D022981:Allelic Imbalance; D000822:Animal Husbandry; D000818:Animals; D002417:Cattle; D002874:Chromosome Mapping / Q000662:veterinary; D005260:Female; D010455:Peptides / Q000235:genetics*; D011247:Pregnancy; D011270:Pregnancy, Animal; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D010455:Peptides; D014157:Transcription Factors