Genome-wide associations with longevity and reproductive traits in U.S. rangeland ewes.

Introduction: Improving ewe longevity is an important breeding and management goal, as death loss and early culling of mature ewes are economic burdens in the sheep industry. Ewe longevity can be improved by selecting for positive reproductive outcomes. However, the breeding approaches for accomplishing this come with the challenge of recording a lifetime trait. Characterizing genetic factors underpinning ewe longevity and related traits could result in the development of genomic selection strategies to improve the stayability of sheep through early, informed selection of replacement ewes. Methods: Towards this aim, a genome-wide association study (GWAS) was performed to identify genetic markers associated with ewe longevity, reproductive, and production traits. Traits evaluated included longevity (i.e., length of time in the flock), parity and the lifetime number of lambs born, lambs born alive, lambs weaned, and weight of lambs weaned. Ewe records from previous studies were used. Specifically, Rambouillet (n = 480), Polypay (n = 404), Suffolk (n = 182), and Columbia (n = 64) breed ewes (N = 1,130) were analyzed against 503,617 SNPs in across-breed and within-breed GWAS conducted with the Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model in R. Results: The across-breed GWAS identified 25 significant SNPs and the within-breed GWAS for Rambouillet, Polypay, and Suffolk ewes identified an additional 19 significant SNPs. The most significant markers were rs411309094 (13:22,467,143) associated with longevity in across-breed GWAS (p-value = 8.3E-13) and rs429525276 (2:148,398,336) associated with both longevity (p-value = 6.4E-15) and parity (p-value = 4.8E-15) in Rambouillet GWAS. Significant SNPs were identified within or in proximity (±50 kb) of genes with known or proposed roles in reproduction, dentition, and the immune system. These genes include ALPL, ANOS1, ARHGEF26, ASIC2, ASTN2, ATP8A2, CAMK2D, CEP89, DISC1, ITGB6, KCNH8, MBNL3, MINDY4, MTSS1, PLEKHA7, PRIM2, RNF43, ROBO2, SLCO1A2, TMEM266, TNFRSF21, and ZNF804B. Discussion: This study proposes multiple SNPs as candidates for use in selection indices and suggests genes for further research towards improving understanding of the genetic factors contributing to longevity, reproductive, and production traits of ewes.

Reducing fecal egg count through selective breeding alters dorper lamb response to Haemonchus contortus in an artificial challenge trial.

Infection by gastrointestinal nematodes (GIN), particularly Haemonchus contortus, can be detrimental to sheep health and performance. Genetic susceptibility to GIN varies between breeds, with those lacking high levels of natural resistance often requiring frequent anthelmintic treatment when facing parasitic challenge. Genetic technology can serve as a tool to decrease GIN susceptibility via selection for sheep with reduced fecal egg count (FEC) estimated breeding values (EBVs). However, the physiological changes that result from implementation of this strategy are not well described. Additionally, there is a need for comparison of animals from recent selective breeding against breeds with inherent GIN resistance. In this study we administered a challenge of H. contortus to Dorper x White Dorper (DWD; n = 92) lambs that have been genetically selected for either low (DWD-) or high (DWD+) FEC EBVs and Barbados Blackbelly x Mouflon (BBM; n = 19) lambs from a genetically resistant breed backgrounds. Lamb FEC, packed-cell volume (PCV) and serum IgG were measured at intermittent levels over 5 weeks. At day 21 and day 35, the selectively bred DWD- had a lower mean FEC compared to DWD+, but were higher than BBM. Reductions in both PCV and serum IgG from initial day 0 levels were observed in DWD lambs, but not in BBM. Furthermore, from a subset of lambs (n = 24) harvested at day 21, DWD- only tended (p = 0.056) to have lower mean worm counts than DWD+, with BBM having the lowest mean worm count. Differentially expressed genes (DEGs) identified via RNA-sequencing of abomasal tissue at day 21 indicate a more pronounced Th2 immune response and more rapid worm expulsion occurred in iBBM than iDWD- and iDWD+ lambs. However, gene expression in DWD- suggests an association between reduced FEC EBV and gastric acid secretion and the ability to limit worm fecundity. Ultimately, selection of Dorper sheep for low FEC EBV can reduce susceptibility to GIN, but it will likely require multiple generations with this trait as a breeding priority before presenting a similar resistance level to Caribbean breeds.

Genome-Wide Analysis of Sheep Artificially or Naturally Infected with Gastrointestinal Nematodes.

The anthelmintic resistance of gastrointestinal nematodes (GINs) poses a significant threat to sheep worldwide, but genomic selection can serve as an alternative to the use of chemical treatment as a solution for parasitic infection. The objective of this study is to conduct genome-wide association studies (GWASs) to identify single nucleotide polymorphisms (SNPs) in Rambouillet (RA) and Dorper × White Dorper (DWD) lambs associated with the biological response to a GIN infection. All lambs were genotyped with a medium-density genomic panel with 40,598 markers used for analysis. Separate GWASs were conducted using fecal egg counts (FECs) from lambs (<1 year of age) that acquired their artificial infections via an oral inoculation of 10,000 Haemonchus contortus larvae (n = 145) or naturally while grazing on pasture (n = 184). A GWAS was also performed for packed cell volume (PCV) in artificially GIN-challenged lambs. A total of 26 SNPs exceeded significance and 21 SNPs were in or within 20 kb of genes such as SCUBE1, GALNT6, IGF1R, CAPZB and PTK2B. The ontology analysis of candidate genes signifies the importance of immune cell development, mucin production and cellular signaling for coagulation and wound healing following epithelial damage in the abomasal gastric pits via H. contortus during GIN infection in lambs. These results add to a growing body of the literature that promotes the use of genomic selection for increased sheep resistance to GINs.

Selecting goats for juniper consumption did not improve their liver Phase I detoxification.

A sodium pentobarbital-induced sleep time study was conducted on 15 adult intact male Boer × Spanish goats selected for high (J+, n = 7) or low (J-, n = 8) juniper consumption (estimated breeding values of 13.1 ± 1.0 and -14.3 ± 0.8, respectively; mean ± standard deviation). Pentobarbital sleep time is an in vivo assay of Phase I hepatic metabolism that can be induced by exposure to barbiturates and monoterpenes. Monoterpenes and pentobarbital are initially oxidized by this pathway; thus, we hypothesized that J+ goats would have shorter sleep times than J- goats. Time to the righting reflex after pentobarbital-induced sleep was measured in all goats following a minimum period of 21 d on three different diets: 1) grazing juniper-infested rangeland (JIR), 2) forage diet with no monoterpenes (M0), and 3) forage diet with 8 g/kg added monoterpenes from camphor, sabinene, and α-pinene in a w/w ratio of 5:4:1 (M+). Fecal samples from the JIR diet were analyzed with near-infrared spectroscopy for the percentage of juniper in the diet. Fecal samples from the JIR and M+ diets were analyzed for camphor and sabinene concentrations. The percentage of juniper in the diet of J+ goats grazing rangelands was greater (P = 0.001) than J- goats (31.1% and 18.6%, respectively). Sleep time did not differ between selection lines (P = 0.36). However, the sleep time of the goats fed M+ diet was 26 min shorter (P < 0.001) than JIR or M0 diets, which were equal. The concentration of camphor and sabinene in the feces was higher (P < 0.001) for goats on the M+ diet than on the JIR diet. There were no differences between selection lines in the serum enzymes indicative of liver disease (aspartate aminotransferase, bilirubin, gamma-glutamyl transferase, and glutamate dehydrogenase; P > 0.12), and all treatment means were within the reference interval. Selecting goats for juniper consumption did not affect the Phase I detoxification system, and several alternative hypotheses for differences in juniper consumption between J+ and J- goats are discussed.

Juniper is an encroaching woody plant with high levels of essential oils and condensed tannins that can limit its consumption by herbivores. Goats were divergently selected for 15 yr to increase or decrease their juniper consumption. This study was conducted to determine if a physiological pathway for metabolism of essential oils differed between high and low juniper-consuming goat lines. The metabolic pathway for the elimination of essential oils is similar to that of the barbiturate pentobarbital. A pentobarbital-induced sleep time was used to detect differences in detoxification rates between the divergent goat lines selectively bred for either a high or low percentage of juniper in their diet. We hypothesized that high juniper-consuming goats would have shorter sleep times, indicating their detoxification pathway was more active. However, there was no difference between these lines. Additionally, there were no differences between the selection lines in blood metabolites that indicate liver tissue damage or liver weights. Therefore, higher dietary juniper preference may be associated with other detoxification mechanisms, may not be limited by essential oils, or may be a socially facilitated learned behavior.

Response of Rambouillet Lambs to an Artificial Gastrointestinal Nematode Infection.

Gastrointestinal nematodes (GIN) threaten the productivity and health of sheep worldwide, prompting the need for genetic selection to reduce GIN susceptibility. Fecal egg count (FEC), packed-cell volume (PCV), and various production traits were examined in parasitized Rambouillet sheep and compared to sire FEC estimated breeding value (EBV). Rambouillet lambs (n = 77) were inoculated with 10,000 H. contortus L3 larvae. Subsequently, FEC, PCV, and body weight (BW) were captured at seven-day intervals for six weeks. Lambs were sired by one of two rams with post-weaning FEC EBV of −9% or +9%. Mean FEC differed (p = 0.0132) with lambs from the lower EBV sire ("Sire L") being reduced, versus those from the higher EBV sire ("Sire H"), being 2135 ± 211 vs. 2912 ± 207 eggs per gram, respectively. Males and females did not differ for FEC, but females exhibited a higher mean PCV than males, (33.74 vs. 29.65%, p < 0.0001). Lambs were shorn ~120 d post artificial infection and wool measurements were captured. A negative correlation between FEC and grease fleece weight was observed. Our results describe the response of Rambouillet lambs to artificial H. contortus infection and suggest FEC EBV can reduce susceptibility to GIN in this breed.