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 cows 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 (NCP 4 ) 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 NCP 4 values selected from 15,225 animals. Results We identified genetic variants on bovine chromosome 12 (BTA12) that were associated with NCP 4 . 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 NCP 4 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 NCP 4 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.

... association study (GWAS) using 688 animals with extreme NCP 4 values selected from 15,225 animals. Results We identified genetic variants on bovine chromosome 12 (BTA12) that were associated with NCP 4 . 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

... 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 NCP 4 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 NCP 4 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. Calving efficiency Number of calves produced at 4 years of age (NCP 4 ) Genome-wide association study General Transcription Factor IIF, polypeptide 2 ( GTF2F2 ) Beef cattle Background Calving efficiency is a major factor in determining the efficiency of beef cattle reproduction

... conditioning, the associations of the other SNPs disappeared (Figure 3 C, Additional file 3 ), indicating that the region contains a single QTL. Variants in the GTF2F2 region were associated with NCP 4 The LD region harbors two genes: General Transcription Factor IIF , polypeptide 2 ( GTF2F2 ) and Potassium Channel Tetramerization domain containing 4 ( KCTD4 ), which is located in intron 4 of GTF2F2 and is transcribed in the opposite direction (Figure 3 A). To detect association polymorphisms in GTF2F2 and KCTD4 , we sequenced all of the exons and upstream regions, beginning 3 kbp upstream of the start codon of each gene in three animals with Q- and q- homozygous haplotype that were defined by the genotypes of BovineHD1200004575 (15,353,468 bp) and BovineHD1200004611 (15,465,327 bp) (Additional files 3 and 4 ). In the GTF2F2 region, we found one synonymous SNP in the coding region, five SNPs and one indel in the upstream region, and we found nine SNPs in the 3' UTR (Additional file 5 ). We also found a non-synonymous SNP (Ile 189 Val) and one indel in the region upstream of KCTD4 (Additional file 5 ). To determine whether these variants of GTF2F2 and KCTD4 are associated with NCP 4 , we genotyped the variants in the GWAS samples and analyzed the association with NCP 4 using EMMAX software with a genetic relationship matrix among animals. There was a total of 16 variants of the GTF2F2 region that produced a highly significant signal ( P = 4.1 10 -5 - 5.28 10 -6 ), whereas the two variants of KCTD4 were not associated with NCP 4 ( P = 0.02 - 0.03). These association studies suggest that the causative variants are located within the GTF2F2 region. Allelic imbalance level of GTF2F2 mRNA We observed that GTF2F2 was expressed in the female reproductive organs as well as other tissues and cells, including fibroblasts (Additional file 6 ). Using an allelic imbalance test [ 8 , 9 ], we compared the relative abundance of Q - versus q -derived transcripts of GTF2F2 in primary dermal

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Gene: GTF2F2 - general transcription factor IIF, polypeptide 2, 30kDa - (NCBI)

Protein : 1f3u

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