Background: Gastrointestinal nematode infection (GNI) is the most important disease affecting the small ruminant industry in U.S. The environmental conditions in the southern United States are ideal for the survival of the most pathogenic gastrointestinal nematode,Haemonchus contortus. Host genetic variation for resistance toH. contortusallows selective breeding for increased resistance of animals. This selection process increases the prevalence of particular alleles in sheep and goats and creates unique genetic patterns in the genome of these species. The aim of this study was to identify loci with divergent allelic frequencies in a candidate gene panel of 100 genes using two different approaches (frequentist and Bayesian) to estimateFst outliers in three different breeds of sheep and goats exposed toH. contortus.Results: Our results for sheep populations showed SNPs under selection inC3AR1,CSF3,SOCS2,NOS2,STAT5B,TGFB2andIL2RAgenes using frequentist and Bayesian approaches. For goats, SNPs inCD1D,ITGA9,IL12A,IL13RA1, CD86andTGFB2genes were under selection. Common signatures of selection in both species were observed inNOS2,TGFB2andTLR4genes. Directional selection was present in all SNPs evaluated in the present study.Conclusions: A total of 13 SNPs within 7 genes of our candidate gene panel related toH. contortusexposure were identified under selection in sheep populations. For goats, 11 SNPs within 7 genes were identified under selection. Results from this study support the hypothesis that resistance toH. contortusis likely to be controlled by many loci. Shared signatures of selection related to mechanisms of immune protection againstH. contortusinfection in sheep and goats could be useful targets in breeding programs aimed to produce resistant animals with low FEC.
Internal parasitism has been the leading cause of morbidity and mortality in small ruminants in many areas such as the southcentral USA. Among the different approaches and management practices to cope with internal parasitism, genetic selection for internal parasite resistance is recognized as one with considerable potential long-term impact. A central performance test with artificial infection of Haemonchus contortus for selection of growing meat goats and hair sheep for breeding to increase resistance to internal parasitism and on-farm selection of females was conducted for 3 years. The results varied considerably among breeds of goats and flocks of sheep. Spanish goats and St. Croix sheep maintained relatively low fecal egg count (FEC) each year, whereas for goats categorized as being of high resistance and Dorper sheep FEC decreased with advancing year. Packed call volume (PCV) and total serum immunoglobulin (Ig) levels were not strongly related to FEC. Genetic parameters varied between the two species, which might be related to previous selection pressure exerted for parasite resistance. Heritability of FEC was higher in goats than sheep. The genetic correlation between FEC and IgM and IgG was negative for both species, which suggests possible genetic association. Genetic and phenotypic correlations between ADG and FEC were nonsignificant for both species. In conclusion, different relationships of FEC and PCV between species require careful attention during selection and the lack of relationship between ADG and FEC suggests that selection of growing male meat goats and hair sheep for resistance to internal parasitism will not adversely affect growth performance.
1 January 2001 in Biological and Pharmaceutical Bulletin
We have estimated the pharmacokinetic and pharmacodynamic interactions of verapamil (VP) enantiomers and also the interaction between VP and its metabolite, norverapamil (NVP). ECGs of conscious rabbits were studied to determine the pharmacokinetics of VP enantiomers and racemic NVP in relation to their prolongation effect on PR intervals, which were used as an index of VP's antiarrhythmic effect. Plasma free fractions of VP enantiomers showed constant values at concentrations ranging from 0.022 to 1.10 microm. There were no interactions between enantiomers or between VP and NVP. The pharmacological effect of the S-enantiomer (S-VP), which was determined by linear regression analysis, showed it was about 20 times more potent than that of the R-enantiomer (R-VP). The effect of racemic VP was the simple sum of those elicited by both enantiomers. These relationships were not significantly different between intravenous infusion and bolus injection. Simultaneous intravenous infusion of NVP had no influence on the PR intervals. In conclusion, we demonstrated that the relationship between plasma unbound concentration of VP enantiomers and their pharmacological effect was the simple sum of two enantiomers.
This publication discusses a research project designed to explore the genetics of resistance to gastrointestinal parasites in sheep and goats. Written by Zaira M. Estrada Reyes, Yoko Tsukahara, Arthur L. Goetsch, Terry A. Gipson, Tilahun Sahlu, Richard Puchala, and Raluca G. Mateescu, and published by the UF/IFAS Department of Animal Sciences, January 2022.
Animal nutrition models can be useful to gain an understanding of factors responsible for and predict biological responses. However, specific models developed can vary among statistical methods employed, especially with relatively small datasets. In this meta-analysis study, independent variables selected by regression tree, stepwise regression, and Least Absolute Shrinkage and Selection Operator (LASSO) analyses were compared. The database consisted of 135 treatment means (weighted by the number observations) from 25 publications in which goats consumed forage ad libitum with or without supplementation and was divided into three subsets of forage with a crude protein (CP) concentration < 6% (Low; n = 46), 6–10% (Moderate; n = 50), and > 10% (High; n = 39). Regression tree analysis was conducted with rpart of the R statistical programming language and stepwise regression (proc stepwise) and LASSO (proc glmselect) were conducted with SAS. The target variable was forage metabolizable energy (ME) intake relative to metabolic body weight (BW0.75) and potential predictor variables were supplement ME intake also scaled to BW0.75, forage organic matter (OM) digestibility and neutral detergent fiber (NDF) concentration, and supplement concentrations of ME and CP. As shown in Table 1, supplement ME intake was selected with each method. Based on the order of selection, forage NDF concentration had larger impact than supplement ME intake with the Low dataset, whereas supplement ME intake was most important with Moderate and High datasets. Among the statistical methods evaluated, selected variables varied most with the Low dataset, were similar for the Moderate dataset, and were the same for Stepwise and LASSO approaches with the High dataset. In conclusion, model development to predict feedstuff associative effects in goats requires careful attention to variable selection that is impacted by statistical method and varies with forage composition.