scholarly journals Determination of Genetic Effects of LIPK and LIPJ Genes on Milk Fatty Acids in Dairy Cattle

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 86 ◽  
Author(s):  
Lijun Shi ◽  
Bo Han ◽  
Lin Liu ◽  
Xiaoqing Lv ◽  
Zhu Ma ◽  
...  

In our previous genome-wide association study (GWAS) on milk fatty acids (FAs) in Chinese Holstein, we discovered 83 genome-wide significant single nucleotide polymorphisms (SNPs) associated with milk FAs. Two of them were close to lipase family member K (LIPK) and lipase family member J (LIPJ), respectively. Hence, this study is a follow-up to verify whether the LIPK and LIPJ have significant genetic effects on milk FAs in dairy cattle. By re-sequencing the entire exons, and 3 kb of 5′ and 3′ flanking regions, two and seven SNPs were identified in LIPK and LIPJ, respectively, including a novel SNP, ss158213049726. With the Haploview 4.1 software, we found that five of the SNPs in LIPJ formed a haplotype block (D′ = 0.96 ~ 1.00). Single-locus association analyses revealed that each SNP in LIPK and LIPJ was significantly associated with at least one milk FA (p = < 1.00×10-4 ~ 4.88×10-2), and the haplotype-based association analyses showed significant genetic effects on nine milk FAs (p = < 1.00×10-4 ~ 3.98×10-2). Out of these SNPs, the missense mutation in LIPK gene, rs42774527, could change the protein secondary structure and function predicted by SOPMA, SIFT, and PROVEAN softwares. With the Genomatix software, we predicted that two SNPs, rs110322221 in LIPK and rs211373799 in LIPJ, altered the transcription factors binding sites (TFBSs), indicating their potential regulation on promoter activity of the genes. Furthermore, we found that both LIPK and LIPJ had relatively high expressions in the mammary gland. In conclusion, our research is the first to demonstrate that LIPK and LIPJ genes have significant associations with milk FAs, and the identified SNPs might be served as genetic markers to optimize breeding programs for milk FAs in dairy cattle. This research deserves in-depth verification.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lijun Shi ◽  
Xin Wu ◽  
Yuze Yang ◽  
Zhu Ma ◽  
Xiaoqing Lv ◽  
...  

Abstract Background People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids (FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study (GWAS) on milk FAs in dairy cattle, 83 genome-wide significant single nucleotide polymorphisms (SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle. Results Through re-sequencing the complete coding region, and 3000 bp of 5′ and 3′ regulatory regions of the AGPAT3 gene, a total of 17 SNPs were identified, including four in 5′ regulatory region, one in 5′ untranslated region (UTR), three in introns, one in 3′ UTR, and eight in 3′ regulatory region. By the linkage disequilibrium (LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs, respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0 (P < 0.0001–0.0384). Further, with Genomatix, we predicted that four SNPs in 5′ regulatory region (g.146702957G > A, g.146704373A > G, g.146704618A > G and g.146704699G > A) changed the transcription factor binding sites (TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373A > G and g.146704618A > G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G (P = 0.0004). Conclusions In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk FAs in dairy cattle, and two potential causal mutations were detected.


2020 ◽  
Author(s):  
Lijun Shi ◽  
Xin Wu ◽  
Zhu Ma ◽  
Xiaoqing Lv ◽  
Lin Liu ◽  
...  

Abstract Background: People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids (FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study (GWAS) on milk FAs in dairy cattle, 83 genome-wide significant single nucleotide polymorphisms (SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.Results: Through re-sequencing the complete coding region, and 3,000bp of 5' and 3' regulatory regions of the AGPAT3 gene, a total of 17 SNPs were identified, including four in 5' regulatory region, one in 5' untranslated region (UTR), three in introns, one in 3' UTR, and eight in 3' regulatory region. By the linkage disequilibrium (LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs, respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1,065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0 (P < 0.0001~ 0.0384). Further, with Genomatix, we predicted that four SNPs in 5' regulatory region (g.146702957G>A, g.146704373A>G g.146704618A>G and g.146704699G>A) changed the transcription factor binding sites (TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373A>G and g.146704618A>G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G (P = 0.0004).Conclusions: In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk FAs in dairy cattle, and two potential causal mutations were detected.


2020 ◽  
Author(s):  
Mingyue Cao ◽  
Lijun Shi ◽  
Peng Peng ◽  
Bo Han ◽  
Lin Liu ◽  
...  

Abstract Background: Our 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.Results: We re-sequenced the entire coding region and 3,000 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 that 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.17305206T>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).Conclusions: In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.


2020 ◽  
Author(s):  
Lijun Shi ◽  
Zhu Ma ◽  
Xiaoqing Lv ◽  
Lin Liu ◽  
Yanhua Li ◽  
...  

Abstract Background: In our previous genome-wide association study (GWAS) on milk fatty acids (FAs) in dairy cattle, 83 genome-wide significant single nucleotide polymorphisms (SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.Results: Through re-sequencing the complete coding region, and 3,000bp of 5' and 3' regulatory regions of the AGPAT3 gene, a total of 17 SNPs were identified, including four in 5' regulatory region, one in 5' untranslated region (UTR), three in introns, one in 3' UTR, and eight in 3' regulatory region. By the linkage disequilibrium (LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs, respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1,065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with medium-chain saturated fatty acids (C6:0, C8:0 and C10:0; P < 0.0001~ 0.0384). Further, with Genomatix, we predicted that four SNPs in 5' regulatory region (g.146702957G>A, g.146704373A>G g.146704618A>G and g.146704699G>A) changed the transcription factor binding sites (TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373A>G and g.146704618A>G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G (P = 0.0004).Conclusions: In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk medium-chain saturated FAs in dairy cattle, and two potential causal mutations were detected.


2020 ◽  
Author(s):  
Lijun Shi ◽  
Xin Wu ◽  
Zhu Ma ◽  
Xiaoqing Lv ◽  
Lin Liu ◽  
...  

Abstract Background: People are paying more attention to the healthy and balanced diet with the improvement of their living standards. Milk fatty acids (FAs) have been reported that they were related to some atherosclerosis and coronary heart diseases in human. In our previous genome-wide association study (GWAS) on milk FAs in dairy cattle, 83 genome-wide significant single nucleotide polymorphisms (SNPs) were detected. Among them, two SNPs, ARS-BFGL-NGS-109493 and BTA-56389-no-rs associated with C18index (P = 0.0459), were located in the upstream of 1-acylglycerol-3-phosphate O-acyltransferase 3 (AGPAT3) gene. AGPAT3 is involved in glycerol-lipid, glycerol-phospholipid metabolism and phospholipase D signaling pathways. Hence, it was inferred as a candidate gene for milk FAs. The aim of this study was to further confirm the genetic effects of the AGPAT3 gene on milk FA traits in dairy cattle.Results: Through re-sequencing the complete coding region, and 3,000bp of 5' and 3' regulatory regions of the AGPAT3 gene, a total of 17 SNPs were identified, including four in 5' regulatory region, one in 5' untranslated region (UTR), three in introns, one in 3' UTR, and eight in 3' regulatory region. By the linkage disequilibrium (LD) analysis with Haploview4.1 software, two haplotype blocks were observed that were formed by four and 12 identified SNPs, respectively. Using SAS9.2, we performed single locus-based and haplotype-based association analysis on 24 milk FAs in 1,065 Chinese Holstein cows, and discovered that all the SNPs and the haplotype blocks were significantly associated with C6:0, C8:0 and C10:0 (P < 0.0001~ 0.0384). Further, with Genomatix, we predicted that four SNPs in 5' regulatory region (g.146702957G>A, g.146704373A>G g.146704618A>G and g.146704699G>A) changed the transcription factor binding sites (TFBSs) for transcription factors SMARCA3, REX1, VMYB, BRACH, NKX26, ZBED4, SP1, USF1, ARNT and FOXA1. Out of them, two SNPs were validated to impact transcriptional activity by performing luciferase assay that the alleles A of both SNPs, g.146704373A>G and g.146704618A>G, increased the transcriptional activities of AGPAT3 promoter compared with alleles G (P = 0.0004).Conclusions: In conclusion, our findings first demonstrated the significant genetic associations of the AGPAT3 gene with milk FAs in dairy cattle, and two potential causal mutations were detected.


BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mingyue Cao ◽  
Lijun Shi ◽  
Peng Peng ◽  
Bo Han ◽  
Lin Liu ◽  
...  

Abstract Background Our 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. Results We 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). Conclusions In conclusion, our findings provided first evidence that the HTR1B gene had significant genetic effects on milk fatty acids in dairy cattle.


2021 ◽  
Vol 1 (19) ◽  
pp. 352-354
Author(s):  
E.A. Gladyr ◽  
L.P. Ignatieva ◽  
I.A. Lashneva ◽  
A.A. Kositsin ◽  
O.A. Artemieva ◽  
...  

The first results of the genome-wide associations analysis for fatty acids composition in cow milk by Russian Holsteinized Black-and-White and Holstein breeds were obtained. Genomic regions (QTL) associated with milk fat percentage, fatty acids synthesis, functional parameters of linear type for udder and leg traits, fertility features have been detected.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 245-246
Author(s):  
Alexander A Sermyagin ◽  
Irina Lashneva ◽  
Larisa P Ignatieva ◽  
Alexander Kositsin ◽  
Elena Gladyr ◽  
...  

Abstract Milk fatty acids (FA) derived from infrared spectra are a new type of traits that allow fast and predictability use their in dairy breeding and herd cattle management. The Holstein animals feature are the high milk yield, but milk composition traits can be different according to population or country origin. The purpose of our study was to find out genetic variation for milk FA and detect QTLs associated with Holstein sires’ EBV in Russian cattle population. For this analysis, we used an experimental dataset for 36982 milk test records from 14 breeding herds in the Moscow region. Individual milk samples per animal analyzed routinely by MilkoScan7 for different FA types: C14:0, C16:0, C18:0, C18:1, saturated, mono- and polyunsaturated, short-, medium- and long-chain. Total number of bulls consisted 778 individuals including 222 animals with genotypes (39051 SNP, Illumina 50K). For calculating EBV by Sire Model, we applied BLUPF90. Plink 1.90 performed quality check control and GWAS procedure. Heritability coefficients were 0.071–0.155 for C14:0-C18:0 levels, 0.196 for C18:1, 0.083 for SFA, 0.018 for PUFA, 0.176 for MUFA, 0.114–0.155 for SCFA-LCFA levels. GWAS revealed most significant (P &lt; 0.001-0.00001) frequently QTLs associated with FA content that were cited in articles previously for BTA5 (CHST11,C18:1), BTA6 (KCNIP4,C18:1; PPRAGC1A,C18:0), BTA11 (NRXN1,LPIN1,C18:1; NBAS,C18:0), BTA26 (PCDH15,PUFA; PRKG1,C18:1). These genes were responsible for synthesis milk fat, fertility, udder conformation traits, lauric, myristic, myristoleic, palmatoleic, oleic and other types of FA. In addition, we identified several QTLs for C14:0, C16:0, SFA, MUFA, SCFA, LCFA on BTA1 (137.32 Mb), BTA10 (5.50 Mb, 9.79 Mb), BTA14 (44.35 Mb), BTA19 (17.57–17.89 Mb) and BTA22 (14.02–14.06 Mb, 20.29–20.45 Mb). Our results are the first steps toward to understanding genetic and genomic mechanisms for using FA in selection processes to improve milk quality for Holstein cattle in Russia. The study was funded by RSF (project No. 21-76-20046)


Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 997 ◽  
Author(s):  
Valdecy A. R. Cruz ◽  
Hinayah R. Oliveira ◽  
Luiz F. Brito ◽  
Allison Fleming ◽  
Steven Larmer ◽  
...  

The identification of genomic regions and candidate genes associated with milk fatty acids contributes to better understand the underlying biology of these traits and enables breeders to modify milk fat composition through genetic selection. The main objectives of this study were: (1) to perform genome-wide association analyses for five groups of milk fatty acids in Holstein cattle using a high-density (777K) SNP panel; and (2) to compare the results of GWAS accounting (or not) for the DGAT1 gene effect as a covariate in the statistical model. The five groups of milk fatty acids analyzed were: (1) saturated (SFA); (2) unsaturated (UFA); (3) short-chain (SCFA); (4) medium-chain (MCFA); and (5) long-chain (LCFA) fatty acids. When DGAT1 was not fitted as a covariate in the model, significant SNPs and candidate genes were identified on BTA5, BTA6, BTA14, BTA16, and BTA19. When fitting the DGAT1 gene in the model, only the MGST1 and PLBD1 genes were identified. Thus, this study suggests that the DGAT1 gene accounts for most of the variability in milk fatty acid composition and the PLBD1 and MGST1 genes are important additional candidate genes in Holstein cattle.


BMC Genetics ◽  
2011 ◽  
Vol 12 (1) ◽  
pp. 43 ◽  
Author(s):  
Aniek C Bouwman ◽  
Henk Bovenhuis ◽  
Marleen HPW Visker ◽  
Johan AM van Arendonk

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