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Associations of SNPs located at candidate genes to bovine growth traits, prioritized with an interaction networks construction approach.

ABSTRACT: For most domestic animal species, including bovines, it is difficult to identify causative genetic variants involved in economically relevant traits. The candidate gene approach is efficient because it investigates genes that are expected to be associated with the expression of a trait and defines whether the genetic variation present in a population is associated with phenotypic diversity. A potential limitation of this approach is the identification of candidates. This study used a bioinformatics approach to identify candidate genes via a search guided by a functional interaction network.A functional interaction network tool, BosNet, was constructed for Bos taurus. Predictions for candidate genes were performed using the guilt-by-association principle in BosNet. Association analyses identified five novel markers within BosNet-prioritized genes that had significant effects on different growth traits in Charolais and Brahman cattle.BosNet is an excellent tool for the identification of single nucleotide polymorphisms that are potentially associated with complex traits.

SUBMITTER: Paredes-Sanchez FA

PROVIDER: S-EPMC4511253 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Associations of SNPs located at candidate genes to bovine growth traits, prioritized with an interaction networks construction approach.

Paredes-Sánchez Francisco Alejandro FA Sifuentes-Rincón Ana María AM Segura Cabrera Aldo A García Pérez Carlos Armando CA Parra Bracamonte Gaspar Manuel GM Ambriz Morales Pascuala P

BMC genetics 20150722

<h4>Background</h4>For most domestic animal species, including bovines, it is difficult to identify causative genetic variants involved in economically relevant traits. The candidate gene approach is efficient because it investigates genes that are expected to be associated with the expression of a trait and defines whether the genetic variation present in a population is associated with phenotypic diversity. A potential limitation of this approach is the identification of candidates. This study ...[more]

PMID: 26198337

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Project description:BackgroundOur previous research identified the Kruppel like factor 6 (KLF6) gene as a prospective candidate for milk production traits in dairy cattle. The expression of KLF6 in the livers of Holstein cows during the peak of lactation was significantly higher than that during the dry and early lactation periods. Notably, it plays an essential role in activating peroxisome proliferator-activated receptor α (PPARα) signaling pathways. The primary aim of this study was to further substantiate whether the KLF6 gene has significant genetic effects on milk traits in dairy cattle.ResultsThrough direct sequencing of PCR products with pooled DNA, we totally identified 12 single nucleotide polymorphisms (SNPs) within the KLF6 gene. The set of SNPs encompasses 7 located in 5' flanking region, 2 located in exon 2 and 3 located in 3' untranslated region (UTR). Of these, the g.44601035G > A is a missense mutation that resulting in the replacement of arginine (CGG) with glutamine (CAG), consequently leading to alterations in the secondary structure of the KLF6 protein, as predicted by SOPMA. The remaining 7 regulatory SNPs significantly impacted the transcriptional activity of KLF6 following mutation (P < 0.005), manifesting as changes in transcription factor binding sites. Additionally, 4 SNPs located in both the UTR and exons were predicted to influence the secondary structure of KLF6 mRNA using the RNAfold web server. Furthermore, we performed the genotype-phenotype association analysis using SAS 9.2 which found all the 12 SNPs were significantly correlated to milk yield, fat yield, fat percentage, protein yield and protein percentage within both the first and second lactations (P < 0.0001 ~ 0.0441). Also, with Haploview 4.2 software, we found the 12 SNPs linked closely and formed a haplotype block, which was strongly associated with five milk traits (P < 0.0001 ~ 0.0203).ConclusionsIn summary, our study represented the KLF6 gene has significant impacts on milk yield and composition traits in dairy cattle. Among the identified SNPs, 7 were implicated in modulating milk traits by impacting transcriptional activity, 4 by altering mRNA secondary structure, and 1 by affecting the protein secondary structure of KLF6. These findings provided valuable molecular insights for genomic selection program of dairy cattle.

Project description:BackgroundOur previous genome-wide association study (GWAS) on milk fatty acid traits in Chinese Holstein cows revealed, the SNP, BTB-01556197, was significantly associated with C10:0 at genome-wide level (P = 0.0239). It was located in the down-stream of 5-hydroxytryptamine receptor 1B (HTR1B) gene that has been shown to play an important role in the regulation of fatty acid oxidation. Hence, we considered it as a promising candidate gene for milk fatty acids in dairy cattle. In this study, we aimed to investigate whether the HTR1B gene had significant genetic effects on milk fatty acid traits.ResultsWe re-sequenced the entire coding region and 3000 bp of 5' and 3' flanking regions of HTR1B gene. A total of 13 SNPs was identified, containing one in 5' flanking region, two in 5' untranslated region (UTR), two in exon 1, five in 3' UTR, and three in 3' flanking region. By performing genotype-phenotype association analysis with SAS9.2 software, we observed that 13 SNPs were significantly associated with medium-chain saturated fatty acids such as C6:0, C8:0 and C10:0 (P < 0.0001 ~ 0.042). With Haploview 4.1 software, linkage disequilibrium (LD) analysis was performed. Two haplotype blocks formed by two and ten SNPs were observed. Haplotype-based association analysis indicated that both haplotype blocks were strongly associated with C6:0, C8:0 and C10:0 as well (P < 0.0001 ~ 0.0071). With regards to the missense mutation in exon 1 (g.17303383G > T) that reduced amino acid change from alanine to serine, we predicted that it altered the secondary structure of HTR1B protein with SOPMA. In addition, we predicted that three SNPs in promoter region, g.17307103A > T, g.17305206 T > G and g.17303761C > T, altered the binding sites of transcription factors (TFs) HMX2, PAX2, FOXP1ES, MIZ1, CUX2, DREAM, and PPAR-RXR by Genomatix. Of them, luciferase assay experiment further confirmed that the allele T of g.17307103A > T significantly increased the transcriptional activity of HTR1B gene than allele A (P = 0.0007).ConclusionsIn conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.

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Associations of SNPs located at candidate genes to bovine growth traits, prioritized with an interaction networks construction approach.

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Associations of SNPs located at candidate genes to bovine growth traits, prioritized with an interaction networks construction approach.

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