Limits...
Molecular Effects of Polymorphism in the 3'UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins.

Sugimoto M, Gotoh Y, Kawahara T, Sugimoto Y - PLoS ONE (2015)

Bottom Line: To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3' untranslated region (UTR) of unc-5 homolog C (UNC5C).G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased.This study provides novel insights into the role of UNC5C during embryonic development.

View Article: PubMed Central - PubMed

Affiliation: National Livestock Breeding Center, Nishigo, Fukushima, Japan.

ABSTRACT
Conception rates among dairy cows in Japan have declined in recent decades. To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3' untranslated region (UTR) of unc-5 homolog C (UNC5C). Cows with higher conception rates carried the A polymorphism in the UNC5C 3'UTR. Luciferase assays and quantitative analysis of allele ratios revealed that UNC5C transcripts with the A polymorphism were expressed at higher levels than those carrying the G polymorphism. UNC5C transmits either pro- or anti-apoptotic signals depending on the availability of its ligand, Netrin-1. UNC5C expression is negatively regulated by reproductive homeobox X-linked 5 (Rhox5), and the Rhox5 locus is methylated by G9a methyltransferase. G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased. Repression of UNC5C, G9a, or Netrin-1 or forced expression of Rhox5 in the anterior nucleus stage inhibited development to the blastocyst stage, suggesting that cows carrying the G polymorphism in UNC5C might have lower conception rates because of the poor development of preimplantation embryos. This study provides novel insights into the role of UNC5C during embryonic development.

No MeSH data available.


Related in: MedlinePlus

The UNC5C 3’UTR SNP is associated with conception rate.A. A pairwise linkage disequilibrium diagram showing a schematic representation of the genes (black arrow) located in the associated region on chromosome 6. The red, black, and blue dots represent the genome-wide significant SNPs, the original SNPs, and the newly developed SNPs, respectively. B. The average conception rate ± SE values for the sires and cows in terms of dEBV. The p-value was calculated using Student’s t-test.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493121&req=5

pone.0131283.g002: The UNC5C 3’UTR SNP is associated with conception rate.A. A pairwise linkage disequilibrium diagram showing a schematic representation of the genes (black arrow) located in the associated region on chromosome 6. The red, black, and blue dots represent the genome-wide significant SNPs, the original SNPs, and the newly developed SNPs, respectively. B. The average conception rate ± SE values for the sires and cows in terms of dEBV. The p-value was calculated using Student’s t-test.

Mentions: The associated region on chromosome 6 harboring the significant SNP, BFGL-NGS-117147, included UNC5C and bone morphogenetic protein receptor type IB (BMPR1B; Fig 2A). To detect possible causative polymorphisms in this region, we sequenced all exons and the 5’ and 3’UTRs of these genes and found 8 novel SNPs (Fig 2A). Reanalysis of the newly developed SNPs demonstrated that UNC5C (A+169G) was the most significant (Table J in S1 File). We also confirmed that the association signal for BFGL-NGS-117147 disappeared when the UNC5C (A+169G) genotype was included as a covariate in logistic regression analysis (p = 0.02). Moreover, we genotyped UNC5C (A+169G) in an additional 2,030 cows and total 2,529 sires and found that cattle harboring the A/A genotype exhibited higher conception rates than those harboring the G/G genotype (Fig 2B). Thus, UNC5C (A+169G) was the most promising causative SNP on chromosome 6.


Molecular Effects of Polymorphism in the 3'UTR of Unc-5 homolog C Associated with Conception Rate in Holsteins.

Sugimoto M, Gotoh Y, Kawahara T, Sugimoto Y - PLoS ONE (2015)

The UNC5C 3’UTR SNP is associated with conception rate.A. A pairwise linkage disequilibrium diagram showing a schematic representation of the genes (black arrow) located in the associated region on chromosome 6. The red, black, and blue dots represent the genome-wide significant SNPs, the original SNPs, and the newly developed SNPs, respectively. B. The average conception rate ± SE values for the sires and cows in terms of dEBV. The p-value was calculated using Student’s t-test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493121&req=5

pone.0131283.g002: The UNC5C 3’UTR SNP is associated with conception rate.A. A pairwise linkage disequilibrium diagram showing a schematic representation of the genes (black arrow) located in the associated region on chromosome 6. The red, black, and blue dots represent the genome-wide significant SNPs, the original SNPs, and the newly developed SNPs, respectively. B. The average conception rate ± SE values for the sires and cows in terms of dEBV. The p-value was calculated using Student’s t-test.
Mentions: The associated region on chromosome 6 harboring the significant SNP, BFGL-NGS-117147, included UNC5C and bone morphogenetic protein receptor type IB (BMPR1B; Fig 2A). To detect possible causative polymorphisms in this region, we sequenced all exons and the 5’ and 3’UTRs of these genes and found 8 novel SNPs (Fig 2A). Reanalysis of the newly developed SNPs demonstrated that UNC5C (A+169G) was the most significant (Table J in S1 File). We also confirmed that the association signal for BFGL-NGS-117147 disappeared when the UNC5C (A+169G) genotype was included as a covariate in logistic regression analysis (p = 0.02). Moreover, we genotyped UNC5C (A+169G) in an additional 2,030 cows and total 2,529 sires and found that cattle harboring the A/A genotype exhibited higher conception rates than those harboring the G/G genotype (Fig 2B). Thus, UNC5C (A+169G) was the most promising causative SNP on chromosome 6.

Bottom Line: To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3' untranslated region (UTR) of unc-5 homolog C (UNC5C).G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased.This study provides novel insights into the role of UNC5C during embryonic development.

View Article: PubMed Central - PubMed

Affiliation: National Livestock Breeding Center, Nishigo, Fukushima, Japan.

ABSTRACT
Conception rates among dairy cows in Japan have declined in recent decades. To enhance our understanding of the genes involved in conception rates, we conducted a genome-wide association study (GWAS) using 822 Holsteins and identified a single-nucleotide polymorphism (SNP) associated with conception rate: A+169G in the 3' untranslated region (UTR) of unc-5 homolog C (UNC5C). Cows with higher conception rates carried the A polymorphism in the UNC5C 3'UTR. Luciferase assays and quantitative analysis of allele ratios revealed that UNC5C transcripts with the A polymorphism were expressed at higher levels than those carrying the G polymorphism. UNC5C transmits either pro- or anti-apoptotic signals depending on the availability of its ligand, Netrin-1. UNC5C expression is negatively regulated by reproductive homeobox X-linked 5 (Rhox5), and the Rhox5 locus is methylated by G9a methyltransferase. G9a-knockout mice have previously been demonstrated to be subfertile, and we found that UNC5C, G9a, and Netrin-1 expression levels increased from the 4-cell stage to the blastocyst stage in fertilized murine embryos, whereas Rhox5 expression decreased. Repression of UNC5C, G9a, or Netrin-1 or forced expression of Rhox5 in the anterior nucleus stage inhibited development to the blastocyst stage, suggesting that cows carrying the G polymorphism in UNC5C might have lower conception rates because of the poor development of preimplantation embryos. This study provides novel insights into the role of UNC5C during embryonic development.

No MeSH data available.


Related in: MedlinePlus