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Candidate gene approach for parasite resistance in sheep--variation in immune pathway genes and association with fecal egg count.

ABSTRACT: Sheep chromosome 3 (Oar3) has the largest number of QTLs reported to be significantly associated with resistance to gastro-intestinal nematodes. This study aimed to identify single nucleotide polymorphisms (SNPs) within candidate genes located in sheep chromosome 3 as well as genes involved in major immune pathways. A total of 41 SNPs were identified across 38 candidate genes in a panel of unrelated sheep and genotyped in 713 animals belonging to 22 breeds across Asia, Europe and South America. The variations and evolution of immune pathway genes were assessed in sheep populations across these macro-environmental regions that significantly differ in the diversity and load of pathogens. The mean minor allele frequency (MAF) did not vary between Asian and European sheep reflecting the absence of ascertainment bias. Phylogenetic analysis revealed two major clusters with most of South Asian, South East Asian and South West Asian breeds clustering together while European and South American sheep breeds clustered together distinctly. Analysis of molecular variance revealed strong phylogeographic structure at loci located in immune pathway genes, unlike microsatellite and genome wide SNP markers. To understand the influence of natural selection processes, SNP loci located in chromosome 3 were utilized to reconstruct haplotypes, the diversity of which showed significant deviations from selective neutrality. Reduced Median network of reconstructed haplotypes showed balancing selection in force at these loci. Preliminary association of SNP genotypes with phenotypes recorded 42 days post challenge revealed significant differences (P<0.05) in fecal egg count, body weight change and packed cell volume at two, four and six SNP loci respectively. In conclusion, the present study reports strong phylogeographic structure and balancing selection operating at SNP loci located within immune pathway genes. Further, SNP loci identified in the study were found to have potential for future large scale association studies in naturally exposed sheep populations.

SUBMITTER: Periasamy K

PROVIDER: S-EPMC3922807 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Candidate gene approach for parasite resistance in sheep--variation in immune pathway genes and association with fecal egg count.

Periasamy Kathiravan K Pichler Rudolf R Poli Mario M Cristel Silvina S Cetrá Bibiana B Medus Daniel D Basar Muladno M A K Thiruvenkadan T Ramasamy Saravanan S Ellahi Masroor Babbar MB Mohammed Faruque F Teneva Atanaska A Shamsuddin Mohammed M Podesta Mario Garcia MG Diallo Adama A

PloS one 20140212 2

Sheep chromosome 3 (Oar3) has the largest number of QTLs reported to be significantly associated with resistance to gastro-intestinal nematodes. This study aimed to identify single nucleotide polymorphisms (SNPs) within candidate genes located in sheep chromosome 3 as well as genes involved in major immune pathways. A total of 41 SNPs were identified across 38 candidate genes in a panel of unrelated sheep and genotyped in 713 animals belonging to 22 breeds across Asia, Europe and South America. ...[more]

PMID: 24533078

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Project description:Fecal egg count (FEC) is an indicative measurement for parasite infection in sheep. Different FEC methods may show inconsistent results. Not accounting for inconsistencies can be problematic when integrating measurements from different FEC methods for genetic evaluation. The objectives of this study were to evaluate the difference in means and variances between two fecal egg counting methods used in sheep-the Modified McMaster (LMMR) and the Triple Chamber McMaster (LTCM); to estimate variance components for the two FEC methods, treating them as two different traits; and to integrate FEC data from the two different methods and estimate genetic parameters for FEC and other gastrointestinal parasite resistance traits. Fecal samples were collected from a commercial Rideau-Arcott sheep farm in Ontario. Fecal egg counting was performed using both LMMR and the LTCM methods. Other parasite resistance trait records were collected from the same farm including eye score (FAMACHA), body condition score (BCS), and body weight (WT). The two FEC methods were highly genetically (0.94) and phenotypically (0.88) correlated. However, the mean and variance between the two FEC methods were significantly different (P < 0.0001). Therefore, re-scaling is required prior to integrating data from the different methods. For the multiple trait analysis, data from the two fecal egg counting methods were integrated (LFEC) by using records for the LMMR when available and replacing missing records with re-standardized LTCM records converted to the same mean and variance of LMMR. Heritability estimates were 0.12 ± 0.04, 0.07 ± 0.05, 0.17 ± 0.06, and 0.24 ± 0.07 for LFEC egg count, FAMACHA, BCS, and WT, respectively. The estimated genetic correlations between FEC and the other parasite resistance traits were low and not significant (P > 0.05) for FAMACHA (r = 0.24 ± 0.32) and WT (r = 0.22 ± 0.19), and essentially zero for BCS (r = -0.03 ± 0.25), suggesting little to no benefit of using such traits as indicators for LFEC.

Project description:BackgroundGenetic selection has proven to be a successful strategy for the sustainable control of gastrointestinal parasitism in sheep. However, little is known on the relationship between resistance to parasites and production traits in dairy breeds. In this study, we estimated the heritabilities and genetic correlations for resistance to parasites and milk production traits in the blond-faced Manech breed. The resistance to parasites of 951 rams from the selection scheme was measured through fecal egg counts (FEC) at 30 days post-infection under experimental conditions. Six milk production traits [milk yield (MY), fat yield (FY), protein yield (PY), fat content (FC), protein content (PC) and somatic cell score (LSCS)], were used in this study and were collected on 140,127 dairy ewes in first lactation, as part of the official milk recording. These ewes were related to the 951 rams (65% of the ewes were daughters of the rams).ResultsFecal egg counts at the end of the first and second infections were moderately heritable (0.19 and 0.37, respectively) and highly correlated (0.93). Heritabilities were moderate for milk yields (ranging from 0.24 to 0.29 for MY, FY and PY) and high for FC (0.35) and PC (0.48). MY was negatively correlated with FC and PC (- 0.39 and - 0.45, respectively). FEC at the end of the second infection were positively correlated with MY, FY and PY (0.28, 0.29 and 0.24, respectively with standard errors of ~ 0.10). These slightly unfavorable correlations indicate that the animals with a high production potential are genetically more susceptible to gastrointestinal parasite infections. A low negative correlation (- 0.17) was also found between FEC after the second infection and LSCS, which suggests that there is a small genetic antagonism between resistance to gastrointestinal parasites and resistance to mastitis, which is another important health trait in dairy sheep.ConclusionsOur results indicate an unfavorable but low genetic relationship between resistance to gastrointestinal parasites and milk production traits in the blond-faced Manech breed. These results will help the breeders' association make decisions about how to include resistance to parasites in the selection objective.

Project description:This study estimated genetic parameters for ewe reproductive traits [number of lambs born (NLB) and weaned (NLW) per ewe lambing] and fecal egg counts (FEC) during the peri-parturient rise (PPR) for use in genetic evaluation of Katahdin sheep. Data included NLB and NLW for 23,060 lambings by 9,295 Katahdin ewes, 1,230 PPR at lambing (PPR0) for 750 ewes, 1,070 PPR at approximately 30 d postpartum (PPR30) for 611 ewes, BW at birth, weaning, and (or) post-weaning for 12,869 lambs, and FEC at weaning and (or) post-weaning for 4,676 lambs. Direct additive, permanent environmental, and residual (co)variances were estimated in univariate and bivariate animal models. Fixed effects included effects of ewe management group and ewe age for all traits, and, for PPR, a continuous effect of days between lambing and measurement. Effects of litter size on PPR0 and number of lambs suckled on PPR30 were included in univariate models but excluded from bivariate models for PPR and NLB or NLW. Heritability estimates in univariate models for NLB, NLW, PPR0, and PPR30 were 0.09 ± 0.01, 0.06 ± 0.01, 0.35 ± 0.06, and 0.24 ± 0.07, respectively. Estimates of permanent environmental variance as a proportion of total phenotypic variance were 0.02 ± 0.01 for NLB, 0.03 ± 0.01 for NLW, 0.05 ± 0.06 for PPR0, and 0.13 ± 0.07 for PPR30. Direct additive, phenotypic, permanent environmental, and residual correlations between NLB and NLW were 0.88 ± 0.03, 0.74 ± 0.004, 0.54 ± 0.15, 0.74 ± 0.003, respectively; corresponding correlations between PPR0 and PPR30 were 0.96 ± 0.07, 0.46 ± 0.03, 0.98 ± 0.50, 0.18 ± 0.05, respectively. The additive genetic correlation (rd) between ewe reproductive traits and PPR ranged from 0.12 to 0.18. Estimates of rd between lamb BW and subsequent ewe NLB and NLW ranged from 0.07 to 0.20, and those between PPR and lamb BW ranged from -0.03 to 0.29. The rd between ewe reproductive traits and lamb FEC ranged from 0.27 to 0.40, and those between PPR and lamb FEC ranged from 0.56 to 0.77. Correlations between maternal additive effects on BW and direct additive effects on PPR were low (-0.08 to 0.10), and those between maternal additive effects on BW and direct additive effects on ewe reproductive traits were variable (-0.36 to 0.11). We conclude that FEC in growing lambs and peri-parturient ewes are controlled by similar genes and that modest, but manageable, genetic antagonisms may exist between FEC and ewe productivity.

Project description:BackgroundOne of the greatest impediments to global small ruminant production is infection with the gastrointestinal parasite, Haemonchus contortus. In recent years there has been considerable interest in the gut microbiota and its impact on health. Relatively little is known about interactions between the gut microbiota and gastrointestinal tract pathogens in sheep. Thus, this study was undertaken to investigate the link between the faecal microbiota of sheep, as a sample representing the gastrointestinal microbiota, and infection with H. contortus.ResultsSheep (n = 28) were experimentally inoculated with 14,000 H. contortus infective larvae. Faecal samples were collected 4 weeks prior to and 4 weeks after infection. Microbial analyses were conducted using automated ribosomal intergenic spacer analysis (ARISA) and 16S rRNA gene sequencing. A comparison of pre-infection microbiota to post-infection microbiota was conducted. A high parasite burden associated with a relatively large change in community composition, including significant (p ≤ 0.001) differences in the relative abundances of Firmicutes and Bacteroidetes following infection. In comparison, low parasite burden associated with a smaller change in community composition, with the relative abundances of the most abundant phyla remaining stable. Interestingly, differences were observed in pre-infection faecal microbiota in sheep that went on to develop a high burden of H. contortus infection (n = 5) to sheep that developed a low burden of infection (n = 5). Differences observed at the community level and also at the taxa level, where significant (p ≤ 0.001) in relative abundance of Bacteroidetes (higher in high parasite burden sheep) and Firmicutes (lower in high parasite burden sheep).ConclusionsThis study reveals associations between faecal microbiota and high or low H. contortus infection in sheep. Further investigation is warranted to investigate causality and the impact of microbiome manipulation.

Project description:BackgroundThe fecal egg count reduction test (FECRT) is recommended to monitor drug efficacy against soil-transmitted helminths (STHs) in public health. However, the impact of factors inherent to study design (sample size and detection limit of the fecal egg count (FEC) method) and host-parasite interactions (mean baseline FEC and aggregation of FEC across host population) on the reliability of FECRT is poorly understood.Methodology/principal findingsA simulation study was performed in which FECRT was assessed under varying conditions of the aforementioned factors. Classification trees were built to explore critical values for these factors required to obtain conclusive FECRT results. The outcome of this analysis was subsequently validated on five efficacy trials across Africa, Asia, and Latin America. Unsatisfactory (<85.0%) sensitivity and specificity results to detect reduced efficacy were found if sample sizes were small (<10) or if sample sizes were moderate (10-49) combined with highly aggregated FEC (k<0.25). FECRT remained inconclusive under any evaluated condition for drug efficacies ranging from 87.5% to 92.5% for a reduced-efficacy-threshold of 90% and from 92.5% to 97.5% for a threshold of 95%. The most discriminatory study design required 200 subjects independent of STH status (including subjects who are not excreting eggs). For this sample size, the detection limit of the FEC method and the level of aggregation of the FEC did not affect the interpretation of the FECRT. Only for a threshold of 90%, mean baseline FEC <150 eggs per gram of stool led to a reduced discriminatory power.Conclusions/significanceThis study confirms that the interpretation of FECRT is affected by a complex interplay of factors inherent to both study design and host-parasite interactions. The results also highlight that revision of the current World Health Organization guidelines to monitor drug efficacy is indicated. We, therefore, propose novel guidelines to support future monitoring programs.

Dataset Information

Candidate gene approach for parasite resistance in sheep--variation in immune pathway genes and association with fecal egg count.

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Candidate gene approach for parasite resistance in sheep--variation in immune pathway genes and association with fecal egg count.

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