Model definition for genetic evaluation of purebred and crossbred lambs including heterosis

Crossbreeding is a common practice among commercial sheep producers to improve animal performance. However, genetic evaluation of U.S. sheep is performed within breed type (terminal sire, semi-prolific, and western range). While incorporating crossbred records may improve assessment of purebreds, it requires accounting for heterotic and breed effects in the evaluation. The objectives of this study were to: 1) describe the development of a paternal composite (PC) line, 2) determine the effect of direct and maternal heterosis on growth traits of crossbred lambs, 3) estimate (co)variance components for direct and maternal additive, and uncorrelated maternal environmental, effects, and 4) provide an interpretation of the estimates of random effects of genetic groups, and to use those solutions to compare the genetic merit of founding breed subpopulations. Data included purebred and crossbred records on birth weight (BN; n = 14,536), pre-weaning weight measured at 39 or 84 d (WN; n = 9,362) depending on year, weaning weight measured at 123 d (WW; n = 9,297), and post-weaning weight measured at 252 d (PW; n = 1,614). Mean (SD) body weights were 5.3 (1.1), 16.8 (3.9) and 28.0 (7.6), 39.1 (7.2), and 54.2 (8.7) kg for BN, WN (at the two ages), WW, and PW, respectively. In designed experiments, the Siremax, Suffolk, Texel, Polypay, Columbia, Rambouillet, and Targhee breeds were compared within the same environment. Estimates of heterotic effects and covariance components were obtained using a multiple trait animal model. Genetic effects based on founders’ breeds were significant and included in the model. Percent estimates of direct heterosis were 2.89 ± 0.61, 2.60 ± 0.65, 4.24 ± 0.56, and 6.09 ± 0.86, and estimates of maternal heterosis were 1.92 ± 0.87, 4.64 ± 0.80, 3.95 ± 0.66, and 4.04 ± 0.91, for BN, WN, WW, and PW, respectively. Correspondingly, direct heritability estimates were 0.17 ± 0.02, 0.13 ± 0.02, 0.17 ± 0.02, and 0.46 ± 0.04 for BN, WN, WW, and PW. Additive maternal effects accounted for trivial variation in PW. For BN, WN, and WW, respectively, maternal heritability estimates were 0.16 ± 0.02, 0.10 ± 0.02, and 0.07 ± 0.01. Uncorrelated maternal environmental effects accounted for little variation in any trait. Direct and maternal heterosis had considerable impact on growth traits, emphasizing the value of crossbreeding and the need to account for heterosis, in addition to breed effects, if crossbred lamb information is included in genetic evaluation. Lay Summary Crossbreeding is common in commercial sheep enterprises. It allows breeds with different attributes to be combined to generate crossbred progeny tailored to production environments and customer preferences. Additionally, crossbreds often benefit from heterosis, performing at levels above the average of their parental breeds. Over two decades, body weights were collected at birth and at pre-weaning, weaning, and post-weaning ages on purebred and crossbred lambs from semi-prolific (Polypay), western range (Columbia, Rambouillet, Targhee), and terminal sire (Siremax, Suffolk, Texel) breeds at the U.S. Sheep Experiment Station. When combined, the value of direct heterosis—that due to a lamb being crossbred—and maternal heterosis—that due to the lamb’s dam being crossbred—increased birth (5%) and post-natal (up to 10%) weights in crossbred lambs. This highlights the value of crossbreeding to the U.S. sheep industry, especially in western range production systems. Genetic variation between and within breeds also was detected for the purebred parental breeds. Such heterotic and breed effects must be accounted for if crossbred performance is to be incorporated in genetic evaluation of purebreds. Therefore, these results provide the foundation for utilizing crossbred information in the evaluation and selection of purebred sheep in the United States

Increased Risk of Chronic Wasting Disease in Rocky Mountain Elk Associated With Decreased Magnesium and Increased Manganese in Brain Tissue

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of Rocky Mountain elk in North America. Recent studies suggest that tissue and blood mineral levels may be valuable in assessing TSE infection in sheep and cattle. The objectives of this study were to examine baseline levels of copper, manganese, magnesium, zinc, selenium, and molybdenum in the brains of Rocky Mountain elk with differing prion genotypes and to assess the association of mineral levels with CWD infection. Elk with leucine at prion position 132 had significantly lower magnesium levels than elk with 2 copies of methionine. Chronic wasting disease-positive elk had significantly lower magnesium than control elk. The incorporation of manganese levels in addition to magnesium significantly refined explanatory ability, even though manganese alone was not significantly associated with CWD. This study demonstrated that mineral analysis may provide an additional disease correlate for assessing CWD risk, particularly in conjunction with genotype

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

Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations

Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10−9). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5–1,100). In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36–3.43). Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection

Genome-Wide Association Identifies <i>SLC2A9</i> and <i>NLN</i> Gene Regions as Associated with Entropion in Domestic Sheep

<div><p>Entropion is an inward rolling of the eyelid allowing contact between the eyelashes and cornea that may lead to blindness if not corrected. Although many mammalian species, including humans and dogs, are afflicted by congenital entropion, no specific genes or gene regions related to development of entropion have been reported in any mammalian species to date. Entropion in domestic sheep is known to have a genetic component therefore, we used domestic sheep as a model system to identify genomic regions containing genes associated with entropion. A genome-wide association was conducted with congenital entropion in 998 Columbia, Polypay, and Rambouillet sheep genotyped with 50,000 SNP markers. Prevalence of entropion was 6.01%, with all breeds represented. Logistic regression was performed in PLINK with additive allelic, recessive, dominant, and genotypic inheritance models. Two genome-wide significant (empirical P<0.05) SNP were identified, specifically markers in <i>SLC2A9</i> (empirical P = 0.007; genotypic model) and near <i>NLN</i> (empirical P = 0.026; dominance model). Six additional genome-wide suggestive SNP (nominal P<1x10^-5) were identified including markers in or near <i>PIK3CB</i> (P = 2.22x10^-6; additive model), <i>KCNB1</i> (P = 2.93x10^-6; dominance model), ZC3H12C (P = 3.25x10^-6; genotypic model), JPH1 (P = 4.68x20^-6; genotypic model), and <i>MYO3B</i> (P = 5.74x10^-6; recessive model). This is the first report of specific gene regions associated with congenital entropion in any mammalian species, to our knowledge. Further, none of these genes have previously been associated with any eyelid traits. These results represent the first genome-wide analysis of gene regions associated with entropion and provide target regions for the development of sheep genetic markers for marker-assisted selection.</p></div

Quantile-quantile plots with all SNP from the genotypic analysis.

<p>Quantile-quantile plots from association with entropion, where the expected distribution is the red line.</p

Genomic regions associated with entropion.

<p>^§: P>0.15</p><p>**: SNP located within gene</p><p>*: SNP located within 35 Kb of gene</p><p>Genomic regions associated with entropion.</p

Association of <i>TMEM8B</i> and <i>SPAG8</i> with Mature Weight in Sheep.

Simple Summar

Development and Validation of an Ovine Progressive Pneumonia Virus Quantitative PCR

Ovine progressive pneumonia virus (OPPV) infects at least one sheep in 81% of U.S. sheep flocks, as determined by serology, and can cause viral mastitis, arthritis, dyspnea, and cachexia. Diagnostic tests that quantify OPPV proviral load in peripheral blood leukocytes (PBL) provide an additional method for identification of infected sheep and may help to further understanding of the pathogenesis of OPPV-induced disease. In this study, we compared a new OPPV real-time quantitative PCR (qPCR) assay specific for the transmembrane region of the envelope gene ( tm ) with a competitive inhibition enzyme-linked immunosorbent assay (cELISA) using 396 PBL samples and sera from Idaho sheep. The OPPV qPCR had a positive concordance of 96.2% ± 2.3% and a negative concordance of 97.7% ± 2.5% compared to the cELISA, with a kappa value of 0.93, indicating excellent agreement between the two tests. In addition, the presence of tm in the three OPPV qPCR-positive and cELISA-negative sheep and in 15 sheep with different OPPV proviral loads was confirmed by cloning and sequencing. These data indicate that the OPPV qPCR may be used as a supplemental diagnostic tool for OPPV infection and for measurement of viral load in PBLs of infected sheep

Ovar-DRB1 haplotypes*2001 and*0301 are associated with sheep growth and ewe lifetime prolificacy

Background: The major histocompatibility complex (MHC) is an organized cluster of tightly linked vertebrate genes with immunological and non-immunological functions. While the important MHC gene DRB1 has been examined in regard to many sheep infectious disease traits, only one study, based on microsatellite markers, has previously examined DRB1 and sheep production traits. Furthermore, to our knowledge no studies have examined DRB1 relationship with lifetime ewe prolificacy traits. Therefore, we analyzed association between the presence of DRB1 SNP haplotypes with internationally recognized standard names and production traits including growth and lifetime prolificacy in 370 Rambouillet, Columbia, and Polypay sheep.BackgroundThe major histocompatibility complex (MHC) is an organized cluster of tightly linked vertebrate genes with immunological and non-immunological functions. While the important MHC gene&nbsp;DRB1&nbsp;has been examined in regard to many sheep infectious disease traits, only one study, based on microsatellite markers, has previously examinedDRB1&nbsp;and sheep production traits. Furthermore, to our knowledge no studies have examined&nbsp;DRB1&nbsp;relationship with lifetime ewe prolificacy traits. Therefore, we analyzed association between the presence of&nbsp;DRB1&nbsp;SNP haplotypes with internationally recognized standard names and production traits including growth and lifetime prolificacy in 370 Rambouillet, Columbia, and Polypay sheep.ResultsThe&nbsp;DRB1&nbsp;*0404 haplotype was associated with increased weaning and mature weights, as well as average daily gain (&Scaron;id&aacute;k&nbsp;P&nbsp;&lt;&nbsp;0.05; corrected for the number of haplotypes tested). Interestingly, the *0404 haplotype also showed a trend toward association with increased total number of lifetime lambs born (&Scaron;id&aacute;k&nbsp;P&nbsp;=&nbsp;0.084) and number of lambs born alive (&Scaron;id&aacute;k&nbsp;P&nbsp;=&nbsp;0.084). In contrast, the&nbsp;DRB1&nbsp;*0141 haplotype was associated with decreased mature weight (&Scaron;id&aacute;k&nbsp;P&nbsp;=&nbsp;0.01).ConclusionsSince the *0404 haplotype was present in all three breeds, these results suggest there is at least one functional mutation in the region that influences growth and prolificacy traits that may be broadly present across several breeds. Furthermore, combined use of the similar *0404 and *0141 multi-marker haplotypes that nonetheless have opposing directions of production trait associations will enhance mutation discovery in this region. If undesirable alleles for underlying mutations can be identified, selective pressure against one or a small number of undesirable alleles may improve production with limited impact on MHC genetic diversity and infectious disease susceptibility.</p