Dataset Information

Association of leptin, toll-like receptor 4, and chemokine receptor of interleukin 8 C-X-C motif single nucleotide polymorphisms with fertility traits in Czech Fleckvieh cattle.

ABSTRACT:

Objective

The use of genetic markers can help to enhance reproduction in cattle, which is a very important trait for profitability in dairy production systems. This study evaluated the association between genotypes of leptin (LEP), toll-like receptor 4 (TLR4), and chemokine receptor of interleukin 8 C-X-C motif (CXCR1) genes and fertility traits in Czech Fleckvieh cattle.

Methods

Phenotypic data from 786 Czech Fleckvieh cows raised on 5 farms in the Czech Republic were used, along with information from the 1st three parities. To determine genotype, the polymerase chain reaction- restriction fragment length polymorphism method was used.

Results

Except for LEP g.-963C>T, all studied genotype frequencies of single nucleotide polymorphisms (SNPs) were distributed according to the Hardy-Weinberg equilibrium. Two LEP SNPs (g.-963C>T and c.357C>T) were associated with the age at the 1st calving, days open (DO), pregnancy rate after 1st service (PR), and calving interval (CLI). In LEP g.-963C>T the TT genotype heifers firstly calved 24 days earlier than CC genotype and the CT genotype cow showed a tendency for shorter DO and higher PR. In LEP c.357C>T we observed longer CLI and DO period in TT cows. In general, we can propose the TT genotype of g.-963C>T as favorable and the TT genotype of c.357C>T as unfavorable for a cow´s fertility. Heterozygotes in TLR4 c.-226C>G were significantly associated with shorter CLI, and presented a nonsignificant tendency to be associated with higher PR. In CXCR1 c.777 C>G, we did not observe any relationship of this SNP with reproduction.

Conclusion

Overall, the results showed that LEP could be an effective marker for improving reproduction in Czech Fleckvieh cattle. This study also provides novel insights into the relationship between TLR4 and CXCR1 SNPs and reproduction in dual-purpose cattle.

SUBMITTER: Jecminkova K

PROVIDER: S-EPMC6212755 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Association of leptin, toll-like receptor 4, and chemokine receptor of interleukin 8 C-X-C motif single nucleotide polymorphisms with fertility traits in Czech Fleckvieh cattle.

Jecminkova Katerina K Müller Uwe U Kyselova Jitka J Sztankoova Zuzana Z Zavadilova Ludmila L Stipkova Miloslava M Majzlik Ivan I

Asian-Australasian journal of animal sciences 20180412 11

<h4>Objective</h4>The use of genetic markers can help to enhance reproduction in cattle, which is a very important trait for profitability in dairy production systems. This study evaluated the association between genotypes of leptin (LEP), toll-like receptor 4 (TLR4), and chemokine receptor of interleukin 8 C-X-C motif (CXCR1) genes and fertility traits in Czech Fleckvieh cattle.<h4>Methods</h4>Phenotypic data from 786 Czech Fleckvieh cows raised on 5 farms in the Czech Republic were used, along ...[more]

PMID: 29642663

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Project description:BackgroundCurrently, genome-wide evaluation of cattle populations is based on SNP-genotyping using ~ 54,000 SNP. Increasing the number of markers might improve genomic predictions and power of genome-wide association studies. Imputation of genotypes makes it possible to extrapolate genotypes from lower to higher density arrays based on a representative reference sample for which genotypes are obtained at higher density.MethodsGenotypes using 639 214 SNP were available for 797 bulls of the Fleckvieh cattle breed. The data set was divided into a reference and a validation population. Genotypes for all SNP except those included in the BovineSNP50 Bead chip were masked and subsequently imputed for animals of the validation population. Imputation of genotypes was performed with Beagle, findhap.f90, MaCH and Minimac. The accuracy of the imputed genotypes was assessed for four different scenarios including 50, 100, 200 and 400 animals as reference population. The reference animals were selected to account for 78.03%, 89.21%, 97.47% and > 99% of the gene pool of the genotyped population, respectively.ResultsImputation accuracy increased as the number of animals and relatives in the reference population increased. Population-based algorithms provided highly reliable imputation of genotypes, even for scenarios with 50 and 100 reference animals only. Using MaCH and Minimac, the correlation between true and imputed genotypes was > 0.975 with 100 reference animals only. Pre-phasing the genotypes of both the reference and validation populations not only provided highly accurate imputed genotypes but was also computationally efficient. Genome-wide analysis of imputation accuracy led to the identification of many misplaced SNP.ConclusionsGenotyping key animals at high density and subsequent population-based genotype imputation yield high imputation accuracy. Pre-phasing the genotypes of the reference and validation populations is computationally efficient and results in high imputation accuracy, even when the reference population is small.

Project description:We observed in PRESTO-Tango β-arrestin recruitment assays that the α1-adrenergic receptor (AR) antagonist prazosin activates chemokine (C-X-C motif) receptor (CXCR)4. This prompted us to further examine this unexpected pharmacological behavior. We screened a panel of 14 α1/2- and β1/2/3-AR antagonists for CXCR4 and atypical chemokine receptor (ACKR)3 agonist activity in PRESTO-Tango assays against the cognate agonist CXCL12. We observed that multiple α1-AR antagonists activate CXCR4 (CXCL12 = prazosin = cyclazosin > doxazosin) and ACKR3 (CXCL12 = prazosin = cyclazosin > alfuzosin = doxazosin = phentolamine > terazosin = silodosin = tamsulosin). The two strongest CXCR4/ACKR3 activators, prazosin and cyclazosin, were selected for a more detailed evaluation. We found that the drugs dose-dependently activate both receptors in β-arrestin recruitment assays, stimulate ERK1/2 phosphorylation in HEK293 cells overexpressing each receptor, and that their effects on CXCR4 could be inhibited with AMD3100. Both α1-AR antagonists induced significant chemical shift changes in the 1H-13C-heteronuclear single quantum correlation spectrum of CXCR4 and ACKR3 in membranes, suggesting receptor binding. Furthermore, prazosin and cyclazosin induced internalization of endogenous CXCR4/ACKR3 in human vascular smooth muscle cells (hVSMC). While these drugs did not in induce chemotaxis in hVSMC, they inhibited CXCL12-induced chemotaxis with high efficacy and potency (IC50: prazosin-4.5 nM, cyclazosin 11.6 pM). Our findings reveal unexpected pharmacological properties of prazosin, cyclazosin, and likely other α1-AR antagonists. The results of the present study imply that prazosin and cyclazosin are biased or partial CXCR4/ACKR3 agonists, which function as potent CXCL12 antagonists. Our findings could provide a mechanistic basis for previously observed anti-cancer properties of α1-AR antagonists and support the concept that prazosin could be re-purposed for the treatment of disease processes in which CXCR4 and ACKR3 are thought to play significant pathophysiological roles, such as cancer metastases or various autoimmune pathologies.

Project description:Low birth weight and postnatal growth restriction are the most evident symptoms of dwarfism. Accompanying skeletal aberrations may compromise the general condition and locomotion of affected individuals. Several paternal half-sibs with a low birth weight and a small size were born in 2013 in the Fleckvieh cattle population.Affected calves were strikingly underweight at birth in spite of a normal gestation length and had craniofacial abnormalities such as elongated narrow heads and brachygnathia inferior. In spite of a normal general condition, their growth remained restricted during rearing. We genotyped 27 affected and 10,454 unaffected animals at 44,672 single nucleotide polymorphisms and performed association tests followed by homozygosity mapping, which allowed us to map the locus responsible for growth failure to a 1.85-Mb segment on bovine chromosome 3. Analysis of whole-genome re-sequencing data from one affected and 289 unaffected animals revealed a 1-bp deletion (g.15079217delC, rs723240647) in the coding region of the GON4L gene that segregated with the dwarfism-associated haplotype. We showed that the deletion induces intron retention and premature termination of translation, which can lead to a severely truncated protein that lacks domains that are likely essential to normal protein function. The widespread use of an undetected carrier bull for artificial insemination has resulted in a tenfold increase in the frequency of the deleterious allele in the female population.A frameshift mutation in GON4L is associated with autosomal recessive proportionate dwarfism in Fleckvieh cattle. The mutation has segregated in the population for more than 50 years without being recognized as a genetic disorder. However, the widespread use of an undetected carrier bull for artificial insemination caused a sudden accumulation of homozygous calves with dwarfism. Our findings provide the basis for genome-based mating strategies to avoid the inadvertent mating of carrier animals and thereby prevent the birth of homozygous calves with impaired growth.

Dataset Information

Association of leptin, toll-like receptor 4, and chemokine receptor of interleukin 8 C-X-C motif single nucleotide polymorphisms with fertility traits in Czech Fleckvieh cattle.

Objective

Methods

Results

Conclusion

Publications

Association of leptin, toll-like receptor 4, and chemokine receptor of interleukin 8 C-X-C motif single nucleotide polymorphisms with fertility traits in Czech Fleckvieh cattle.

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