Dataset Information

Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows.

ABSTRACT: The objectives of this study were to identify loci, positional candidate genes, gene-sets, and pathways associated with spontaneous abortion (SA) in cattle and compare these results with previous human SA studies to determine if cattle are a good SA model for humans. Pregnancy was determined at gestation day 35 for Holstein heifers and cows. Genotypes from 43,984 SNPs of 499 pregnant heifers and 498 pregnant cows that calved at full term (FT) were compared to 62 heifers and 28 cows experiencing SA. A genome-wide association analysis, gene-set enrichment analysis-single nucleotide polymorphism, and ingenuity pathway analysis were used to identify regions, pathways, and master regulators associated with SA in heifers, cows, and a combined population. Twenty-three loci and 21 positional candidate genes were associated (p < 1 × 10-5) with SA and one of these (KIR3DS1) has been associated with SA in humans. Eight gene-sets (NES > 3.0) were enriched in SA and one was previously reported as enriched in human SA. Four master regulators (p < 0.01) were associated with SA within two populations. One locus associated with SA was validated and 39 positional candidate and leading-edge genes and 2 gene-sets were enriched in SA in cattle and in humans.

SUBMITTER: Oliver KF

PROVIDER: S-EPMC6969913 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows.

Oliver Kayleen F KF Wahl Alexandria M AM Dick Mataya M Toenges Jewel A JA Kiser Jennifer N JN Galliou Justine M JM Moraes Joao G N JGN Burns Gregory W GW Dalton Joseph J Spencer Thomas E TE Neibergs Holly L HL

Genes 20191121 12

<h4>Background</h4>The objectives of this study were to identify loci, positional candidate genes, gene-sets, and pathways associated with spontaneous abortion (SA) in cattle and compare these results with previous human SA studies to determine if cattle are a good SA model for humans. Pregnancy was determined at gestation day 35 for Holstein heifers and cows. Genotypes from 43,984 SNPs of 499 pregnant heifers and 498 pregnant cows that calved at full term (FT) were compared to 62 heifers and 28 ...[more]

PMID: 31766405

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Project description:BACKGROUND:Subfertility is a major issue facing the dairy industry as the average US Holstein cow conception rate (CCR) is approximately 35%. The genetics underlying the physiological processes responsible for CCR, the proportion of cows able to conceive and maintain a pregnancy at each breeding, are not well characterized. The objectives of this study were to identify loci, positional candidate genes, and transcription factor binding sites (TFBS) associated with CCR and determine if there was a genetic correlation between CCR and milk production in primiparous Holstein cows. Cows were bred via artificial insemination (AI) at either observed estrus or timed AI and pregnancy status was determined at day 35 post-insemination. Additive, dominant, and recessive efficient mixed model association expedited (EMMAX) models were used in two genome-wide association analyses (GWAA). One GWAA focused on CCR at first service (CCR1) comparing cows that conceived and maintained pregnancy to day 35 after the first AI (n = 494) to those that were open after the first AI (n = 538). The second GWAA investigated loci associated with the number of times bred (TBRD) required for conception in cows that either conceived after the first AI (n = 494) or repeated services (n = 472). RESULTS:The CCR1 GWAA identified 123, 198, and 76 loci associated (P < 5 × 10- 08) in additive, dominant, and recessive models, respectively. The TBRD GWAA identified 66, 95, and 33 loci associated (P < 5 × 10- 08) in additive, dominant, and recessive models, respectively. Four of the top five loci were shared in CCR1 and TBRD for each GWAA model. Many of the associated loci harbored positional candidate genes and TFBS with putative functional relevance to fertility. Thirty-six of the loci were validated in previous GWAA studies across multiple breeds. None of the CCR1 or TBRD associated loci were associated with milk production, nor was their significance with phenotypic and genetic correlations to 305-day milk production. CONCLUSIONS:The identification and validation of loci, positional candidate genes, and TFBS associated with CCR1 and TBRD can be utilized to improve, and further characterize the processes involved in cattle fertility.

Project description:BackgroundThe objective was to characterize the colostrum proteome of primiparous Holstein cows in association with immunoglobulin G (IgG) content. Immediately after calving, colostrum samples were collected from 18 cows to measure IgG concentration. Based on colostrum IgG content, samples were classified through cluster analysis and were identified as poor, average, and excellent quality. The proteome was assessed with quantitative shotgun proteomics; abundance data were compared among the colostrum types; enrichment analysis of metabolic processes and proteins classes was performed as well. We also tested correlations between this proteome and blood globulin level of cows and passive immunity level of calves.ResultsOn average, 428 proteins were identified per sample, which belonged mainly to cellular process, biological regulation, response to stimulus, metabolic process, and immune system process. Most abundant proteins were complement C3 (Q2UVX4), alpha-S1-casein (P02662), Ig-like domain-containing protein (A0A3Q1M032), albumin (A0A140T897), polymeric immunoglobulin receptor (P81265), lactotransferrrin (P24627), and IGHG1*01 (X16701_4). Colostrum of excellent quality had greater (P < 0.05) abundance of serpin A3-7 (A2I7N3), complement factor I (A0A3Q1MIF4), lipocalin/cytosolic fatty-acid binding domain-containing protein (A0A3Q1MRQ2), complement C3 (E1B805), complement component 4 binding protein alpha (A0AAF6ZHP5), and complement component C6 (F1MM86). However, colostrum of excellent quality had lower (P < 0.05) abundance of HGF activator (E1BCW0), alpha-S1-casein (P02662), and xanthine dehydrogenase/oxidase (P80457). This resulted in enrichment of the biological processes predominantly for complement activation alternative pathway, complement activation, complement activation classical pathway, humoral immune response, leukocyte mediated immunity, and negative regulation of endopeptidase activity in excellent-quality colostrum. Additionally, some colostrum proteins were found to be correlated with the blood globulin level of cows and with the passive immunity level of calves (P < 0.05; r ≥ 0.57).ConclusionsThis study provides new insights into the bovine colostrum proteome, demonstrating associations between IgG levels and the abundance of other proteins, as well as the enrichment of metabolic processes related to innate immune response. Thus, results suggest that the colostrum proteomic profile is associated with the content of IgG. Future research should deeply explore the association of these findings with pre-calving nutrition status and blood composition of the cow, and with passive immunity transfer to the calf.

Project description:The main objective of this study was to analyze the effects of the inbreeding degree in high-producing primiparous dairy cows genotypically and phenotypically evaluated and its impacts on production and reproductive parameters. Eighty Holstein-Friesian primiparous cows (age: ~26 months; ~450 kg body weight) were previously genomically analyzed to determine the Inbreeding Index (II) and were divided into two groups: low inbreeding group (LI: <2.5; n = 40) and high inbreeding group (HI: ≥2.5 and ≤5.0; n = 40). Genomic determinations of production and reproductive parameters (14 in total), together with analyses of production (12) and reproductive (11) phenotypic parameters (23 in total) were carried out. Statistically significant differences were obtained between groups concerning the genomic parameters of Milk Production at 305 d and Protein Production at 305 d and the reproductive parameter Daughter Calving Ease, the first two being higher in cows of the HI group and the third lower in the LI group (p < 0.05). For the production phenotypic parameters, statistically significant differences were observed between both groups in the Total Fat, Total Protein, and Urea parameters, the first two being higher in the LI group (p < 0.05). Also, significant differences were observed in several reproductive phenotypic parameters, such as Number of Services per Conception, Calving to Conception Interval, Days Open Post Service, and Current Inter-Partum Period, all of which negatively influenced the HI group (p < 0.05). In addition, correlation analyses were performed between production and reproductive genomic parameters separately and in each consanguinity group. The results showed multiple positive and negative correlations between the production and reproductive parameters independently of the group analyzed, being these correlations more remarkable for the reproductive parameters in the LI group and the production parameters in the HI group (p < 0.05). In conclusion, the degree of inbreeding significantly influenced the results, affecting different genomic and phenotypic production and reproductive parameters in high-producing primiparous cows. The determination of the II in first-calf heifers is crucial to evaluate the negative effects associated with homozygosity avoiding an increase in inbreeding depression on production and reproductive traits.

Project description:BACKGROUND:In a beef cattle facility an outbreak of abortions occurred over a 36-day period and included samples from two aborted (non-viable) fetuses and 21 post-abortion clinical cases. There are numerous etiologies, including clinical listeriosis. At the species level, Listeria monocytogenes is ubiquitous in cattle production environments, including soil, feed, and occasionally water sources, and is a common enteric resident of cattle and other mammals. There are four genetically distinct lineages of L. monocytogenes (I-IV), with most lineage III and IV isolates obtained from ruminants. Definitive diagnosis of L. monocytogenes as a causative agent in disease outbreaks relies upon case identification, appropriate sample collection, and laboratory confirmation. Furthermore, clearly establishing a relationship between a pathogen source and clinical disease is difficult. RESULTS:Of the two fetal and 21 clinical case submissions, 19 were positive for L. monocytogenes. Subsequent culture for L. monocytogenes from water and silage sources identified both as potential origins of infection. Using whole-genome sequencing and phylogenetic analyses, clinical, water and silage L. monocytogenes strains grouped into two of four lineages. All water and silage strains, plus 11 clinical strains placed in lineage III, with identical or nearly identical genomic sequences. The remaining eight clinical strains placed in lineage I, with seven having nearly identical sequences and one distinctly different. CONCLUSION:Three genetically distinct strains within two lineages of L. monocytogenes caused the abortion outbreak. The etiology of abortion in 11 cases was directly linked to water and silage contamination from a lineage III L. monocytogenes strain. The source of infection for the remaining abortion cases with two different strains from lineage I is unknown. This is the first report of L. monocytogenes genomics being used as part of an outbreak investigation of cattle abortion.

Project description:BackgroundAt the current price, the use of high-density single nucleotide polymorphisms (SNP) genotyping assays in genomic selection of dairy cattle is limited to applications involving elite sires and dams. The objective of this study was to evaluate the use of low-density assays to predict direct genomic value (DGV) on five milk production traits, an overall conformation trait, a survival index, and two profit index traits (APR, ASI).MethodsDense SNP genotypes were available for 42,576 SNP for 2,114 Holstein bulls and 510 cows. A subset of 1,847 bulls born between 1955 and 2004 was used as a training set to fit models with various sets of pre-selected SNP. A group of 297 bulls born between 2001 and 2004 and all cows born between 1992 and 2004 were used to evaluate the accuracy of DGV prediction. Ridge regression (RR) and partial least squares regression (PLSR) were used to derive prediction equations and to rank SNP based on the absolute value of the regression coefficients. Four alternative strategies were applied to select subset of SNP, namely: subsets of the highest ranked SNP for each individual trait, or a single subset of evenly spaced SNP, where SNP were selected based on their rank for ASI, APR or minor allele frequency within intervals of approximately equal length.ResultsRR and PLSR performed very similarly to predict DGV, with PLSR performing better for low-density assays and RR for higher-density SNP sets. When using all SNP, DGV predictions for production traits, which have a higher heritability, were more accurate (0.52-0.64) than for survival (0.19-0.20), which has a low heritability. The gain in accuracy using subsets that included the highest ranked SNP for each trait was marginal (5-6%) over a common set of evenly spaced SNP when at least 3,000 SNP were used. Subsets containing 3,000 SNP provided more than 90% of the accuracy that could be achieved with a high-density assay for cows, and 80% of the high-density assay for young bulls.ConclusionsAccurate genomic evaluation of the broader bull and cow population can be achieved with a single genotyping assays containing ~ 3,000 to 5,000 evenly spaced SNP.

Dataset Information

Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows.

Publications

Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows.

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