Global assessment of effective population sizes: Consistent taxonomic differences in meeting the 50/500 rule.

Effective population size (Ne) is a particularly useful metric for conservation as it affects genetic drift, inbreeding and adaptive potential within populations. Current guidelines recommend a minimum Ne of 50 and 500 to avoid short-term inbreeding and to preserve long-term adaptive potential respectively. However, the extent to which wild populations reach these thresholds globally has not been investigated, nor has the relationship between Ne and human activities. Through a quantitative review, we generated a dataset with 4610 georeferenced Ne estimates from 3829 populations, extracted from 723 articles. These data show that certain taxonomic groups are less likely to meet 50/500 thresholds and are disproportionately impacted by human activities; plant, mammal and amphibian populations had a <54% probability of reaching N ̂ e = 50 and a <9% probability of reaching N ̂ e = 500. Populations listed as being of conservation concern according to the IUCN Red List had a smaller median N ̂ e than unlisted populations, and this was consistent across all taxonomic groups. N ̂ e was reduced in areas with a greater Global Human Footprint, especially for amphibians, birds and mammals, however relationships varied between taxa. We also highlight several considerations for future works, including the role that gene flow and subpopulation structure plays in the estimation of N ̂ e in wild populations, and the need for finer-scale taxonomic analyses. Our findings provide guidance for more specific thresholds based on Ne and help prioritise assessment of populations from taxa most at risk of failing to meet conservation thresholds.

Deep learning for automated detection of generalized paroxysmal fast activity in Lennox-Gastaut syndrome.

OBJECTIVES: Generalized paroxysmal fast activity (GPFA) is a key electroencephalographic (EEG) feature of Lennox-Gastaut Syndrome (LGS). Automated analysis of scalp EEG has been successful in detecting more typical abnormalities. Automatic detection of GPFA has been more challenging, due to its variability from patient to patient and similarity to normal brain rhythms. In this work, a deep learning model is investigated for detection of GPFA events and estimating their overall burden from scalp EEG. METHODS: Data from 10 patients recorded during four ambulatory EEG monitoring sessions are used to generate and validate the model. All patients had confirmed LGS and were recruited into a trial for thalamic deep-brain stimulation therapy (ESTEL Trial). RESULTS: The correlation coefficient between manual and model estimates of event counts was r2 = 0.87, and for total burden was r2 = 0.91. The average GPFA detection sensitivity was 0.876, with an average false-positive rate of 3.35 per minute. There was no significant difference found between patients with early or delayed deep brain stimulation (DBS) treatment, or those with active vagal nerve stimulation (VNS). CONCLUSIONS: Overall, the deep learning model was able to accurately detect GPFA and provide accurate estimates of the overall GPFA burden and electrographic event counts, albeit with a high false-positive rate. SIGNIFICANCE: Automated GPFA detection may enable automated calculation of EEG biomarkers of burden of disease in LGS.

DNA methylation networks underlying mammalian traits.

Using DNA methylation profiles (n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels in HOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.

Demographic resilience of brook trout populations subjected to experimental size-selective harvesting.

Sustainable management of exploited populations benefits from integrating demographic and genetic considerations into assessments, as both play a role in determining harvest yields and population persistence. This is especially important in populations subject to size-selective harvest, because size selective harvesting has the potential to result in significant demographic, life-history, and genetic changes. We investigated harvest-induced changes in the effective number of breeders ( N ^ b ) for introduced brook trout populations (Salvelinus fontinalis) in alpine lakes from western Canada. Three populations were subject to 3 years of size-selective harvesting, while three control populations experienced no harvest. The N ^ c decreased consistently across all harvested populations (on average 60.8%) but fluctuated in control populations. There were no consistent changes in N ^ b between control or harvest populations, but one harvest population experienced a decrease in N ^ b of 63.2%. The N ^ b / N ^ c ratio increased consistently across harvest lakes; however we found no evidence of genetic compensation (where variance in reproductive success decreases at lower abundance) based on changes in family evenness ( FE ^ ) and the number of full-sibling families ( N ^ fam ). We found no relationship between FE ^ and N ^ c or between N ^ fam / N ^ c and FE ^ . We posit that change in N ^ b was buffered by constraints on breeding habitat prior to harvest, such that the same number of breeding sites were occupied before and after harvest. These results suggest that effective size in harvested populations may be resilient to considerable changes in Nc in the short-term, but it is still important to monitor exploited populations to assess the risk of inbreeding and ensure their long-term survival.

Population Genomics of New Zealand Pouched Lamprey (kanakana; piharau; Geotria australis).

Pouched lamprey (Geotria australis) or kanakana/piharau is a culturally and ecologically significant jawless fish that is distributed throughout Aotearoa New Zealand. Despite its importance, much remains unknown about historical relationships and gene flow between populations of this enigmatic species within New Zealand. To help inform management, we assembled a draft G. australis genome and completed the first comprehensive population genomics analysis of pouched lamprey within New Zealand using targeted gene sequencing (Cyt-b and COI) and restriction site-associated DNA sequencing (RADSeq) methods. Employing 16 000 genome-wide single nucleotide polymorphisms (SNPs) derived from RADSeq (n = 186) and sequence data from Cyt-b (766 bp, n = 94) and COI (589 bp, n = 20), we reveal low levels of structure across 10 sampling locations spanning the species range within New Zealand. F-statistics, outlier analyses, and STRUCTURE suggest a single panmictic population, and Mantel and EEMS tests reveal no significant isolation by distance. This implies either ongoing gene flow among populations or recent shared ancestry among New Zealand pouched lamprey. We can now use the information gained from these genetic tools to assist managers with monitoring effective population size, managing potential diseases, and conservation measures such as artificial propagation programs. We further demonstrate the general utility of these genetic tools for acquiring information about elusive species.

Genetic variation in skin traits in New Zealand lambs.

BACKGROUND: This study explored the genetic variability in the New Zealand sheep population for economically important skin traits. Skins were collected at slaughter from two progeny test flocks, resulting in 725 skins evaluated for grain strain, flatness, crust leather strength and overall suitability for shoe leather. DNA profiles collected from skins post-slaughter were matched to individual animals using previously collected high-density genotypes. RESULTS: Considerable phenotypic variation for skin traits was observed, with around 40% of the skins being identified as suitable for high-value shoe leather production. Several key traits associated with leather production, including flatness, tear strength, grain strength and grain strain were found to be moderate to highly heritable (h2 = 0.28-0.82). There were no major significant genome-wide association study (GWAS) peaks associated with many of the traits examined, however, one single-nucleotide polymorphism (SNP) reached significance for the flatness of the skin over the hindquarters. CONCLUSION: This research confirms that suitable lamb skins can be bred for use as high-value shoe leather. While moderately to highly heritable, skin traits in New Zealand lambs appear to be polygenic with no genes of major effect underlaying the traits of interest. Given the complex nature of these traits, the identification and selection of animals with higher-value skins may be enabled by geomic selection. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Across-country genomic predictions in Norwegian and New Zealand Composite sheep populations with similar development history.

The goal of this study was to assess the feasibility of across-country genomic predictions in Norwegian White Sheep (NWS) and New Zealand Composite (NZC) sheep populations with similar development history. Different training populations were evaluated (i.e., including only NWS or NZC, or combining both populations). Predictions were performed using the actual phenotypes (normalized) and the single-step GBLUP via Bayesian inference. Genotyped NWS animals born in 2016 (N = 267) were used to assess the accuracy and bias of genomic estimated breeding values (GEBVs) predicted for birth weight (BW), weaning weight (WW), carcass weight (CW), EUROP carcass classification (EUC), and EUROP fat grading (EUF). The accuracy and bias of GEBVs differed across traits and training population used. For instance, the GEBV accuracies ranged from 0.13 (BW) to 0.44 (EUC) for GEBVs predicted including only NWS, from 0.06 (BW) to 0.15 (CW) when including only NZC, and from 0.10 (BW) to 0.41 (EUC) when including both NWS and NZC animals in the training population. The regression coefficients used to assess the spread of GEBVs (bias) ranged from 0.26 (BW) to 0.64 (EUF) for only NWS, 0.10 (EUC) to 0.52 (CW) for only NZC, and from 0.42 (WW) to 2.23 (EUC) for both NWS and NZC in the training population. Our findings suggest that across-country genomic predictions based on ssGBLUP might be possible for NWS and NZC, especially for novel traits.

Genomic Tools for the Identification of Loci Associated with Facial Eczema in New Zealand Sheep.

Facial eczema (FE) is a significant metabolic disease that affects New Zealand ruminants. Ingestion of the mycotoxin sporidesmin leads to liver and bile duct damage, which can result in photosensitisation, reduced productivity and death. Strategies used to manage the incidence and severity of the disease include breeding. In sheep, there is considerable genetic variation in the response to FE. A commercial testing program is available for ram breeders who aim to increase tolerance, determined by the concentration of the serum enzyme, gamma-glutamyltransferase 21 days after a measured sporidesmin challenge (GGT21). Genome-wide association studies were carried out to determine regions of the genome associated with GGT21. Two regions on chromosomes 15 and 24 are reported, which explain 5% and 1% of the phenotypic variance in the response to FE, respectively. The region on chromosome 15 contains the ß-globin locus. Of the significant SNPs in the region, one is a missense variant within the haemoglobin subunit ß (HBB) gene. Mass spectrometry of haemoglobin from animals with differing genotypes at this locus indicated that genotypes are associated with different forms of adult ß-globin. Haemoglobin haplotypes have previously been associated with variation in several health-related traits in sheep and warrant further investigation regarding their role in tolerance to FE in sheep. We show a strategic approach to the identification of regions of importance for commercial breeding programs with a combination of discovery, statistical and biological validation. This study highlights the power of using increased density genotyping for the identification of influential genomic regions, combined with subsequent inclusion on lower density genotyping platforms.

Computer-assisted EEG diagnostic review for idiopathic generalized epilepsy.

Epilepsy diagnosis can be costly, time-consuming, and not uncommonly inaccurate. The reference standard diagnostic monitoring is continuous video-electroencephalography (EEG) monitoring, ideally capturing all events or concordant interictal discharges. Automating EEG data review would save time and resources, thus enabling more people to receive reference standard monitoring and also potentially heralding a more quantitative approach to therapeutic outcomes. There is substantial research into the automated detection of seizures and epileptic activity from EEG. However, automated detection software is not widely used in the clinic, and despite numerous published algorithms, few methods have regulatory approval for detecting epileptic activity from EEG. This study reports on a deep learning algorithm for computer-assisted EEG review. Deep convolutional neural networks were trained to detect epileptic discharges using a preexisting dataset of over 6000 labelled events in a cohort of 103 patients with idiopathic generalized epilepsy (IGE). Patients underwent 24-hour ambulatory outpatient EEG, and all data were curated and confirmed independently by two epilepsy specialists (Seneviratne et al., 2016). The resulting automated detection algorithm was then used to review diagnostic scalp EEG for seven patients (four with IGE and three with events mimicking seizures) to validate performance in a clinical setting. The automated detection algorithm showed state-of-the-art performance for detecting epileptic activity from clinical EEG, with mean sensitivity of >95% and corresponding mean false positive rate of 1 detection per minute. Importantly, diagnostic case studies showed that the automated detection algorithm reduced human review time by 80%-99%, without compromising event detection or diagnostic accuracy. The presented results demonstrate that computer-assisted review can increase the speed and accuracy of EEG assessment and has the potential to greatly improve therapeutic outcomes. This article is part of the Special Issue "NEWroscience 2018".

Development of Epigenetic Clocks for Key Ruminant Species.

Robust biomarkers of chronological age have been developed in humans and model mammalian species such as rats and mice using DNA methylation data. The concept of these so-called "epigenetic clocks" has emerged from a large body of literature describing the relationship between genome-wide methylation levels and age. Epigenetic clocks exploit this phenomenon and use small panels of differentially methylated cytosine (CpG) sites to make robust predictions of chronological age, independent of tissue type. Here, we present highly accurate livestock epigenetic clocks for which we have used the custom mammalian methylation array "HorvathMammalMethyl40" to construct the first epigenetic clock for domesticated goat (Capra hircus), cattle (Bos taurus), Red (Cervus elaphus) and Wapiti deer (Cervus canadensis) and composite-breed sheep (Ovis aries). Additionally, we have constructed a 'farm animal clock' for all species included in the study, which will allow for robust predictions to be extended to various breeds/strains. The farm animal clock shows similarly high accuracy to the individual species' clocks (r > 0.97), utilizing only 217 CpG sites to estimate age (relative to the maximum lifespan of the species) with a single mathematical model. We hypothesise that the applications of this livestock clock could extend well beyond the scope of chronological age estimates. Many independent studies have demonstrated that a deviation between true age and clock derived molecular age is indicative of past and/or present health (including stress) status. There is, therefore, untapped potential to utilize livestock clocks in breeding programs as a predictor for age-related production traits.

Global Analysis of Transcription Start Sites in the New Ovine Reference Genome (Oar rambouillet v1.0).

The overall aim of the Ovine FAANG project is to provide a comprehensive annotation of the new highly contiguous sheep reference genome sequence (Oar rambouillet v1.0). Mapping of transcription start sites (TSS) is a key first step in understanding transcript regulation and diversity. Using 56 tissue samples collected from the reference ewe Benz2616, we have performed a global analysis of TSS and TSS-Enhancer clusters using Cap Analysis Gene Expression (CAGE) sequencing. CAGE measures RNA expression by 5' cap-trapping and has been specifically designed to allow the characterization of TSS within promoters to single-nucleotide resolution. We have adapted an analysis pipeline that uses TagDust2 for clean-up and trimming, Bowtie2 for mapping, CAGEfightR for clustering, and the Integrative Genomics Viewer (IGV) for visualization. Mapping of CAGE tags indicated that the expression levels of CAGE tag clusters varied across tissues. Expression profiles across tissues were validated using corresponding polyA+ mRNA-Seq data from the same samples. After removal of CAGE tags with <10 read counts, 39.3% of TSS overlapped with 5' ends of 31,113 transcripts that had been previously annotated by NCBI (out of a total of 56,308 from the NCBI annotation). For 25,195 of the transcripts, previously annotated by NCBI, no TSS meeting stringent criteria were identified. A further 14.7% of TSS mapped to within 50 bp of annotated promoter regions. Intersecting these predicted TSS regions with annotated promoter regions (±50 bp) revealed 46% of the predicted TSS were "novel" and previously un-annotated. Using whole-genome bisulfite sequencing data from the same tissues, we were able to determine that a proportion of these "novel" TSS were hypo-methylated (32.2%) indicating that they are likely to be reproducible rather than "noise". This global analysis of TSS in sheep will significantly enhance the annotation of gene models in the new ovine reference assembly. Our analyses provide one of the highest resolution annotations of transcript regulation and diversity in a livestock species to date.

Genetic Connectedness Between Norwegian White Sheep and New Zealand Composite Sheep Populations With Similar Development History.

The Norwegian White sheep (NWS) and New Zealand Terminal Sire Composite (NZC) sheep breeds have been developed based on crossing of multiple breeds, mainly of Northern European origin. A close genetic relationship between these populations could enable across-country genomic evaluations. The main objectives of this study were to assess the genetic connectedness between Norwegian and New Zealand sheep populations and estimate numerous genetic diversity metrics for these two populations. A total of 792 NWS and 16,912 NZC animals were genotyped using a high-density Illumina SNP chip panel (∼606K SNPs). The NZC animals were grouped based on their breed composition as: Finn, Lamb Supreme, Primera, Texel, "Other Dual Purpose", and "Other Terminal Sire". The average level of linkage disequilibrium ranged from 0.156 (for Primera) to 0.231 (for Finn). The lowest consistency of gametic phase was estimated between NWS and Finn (0.397), and between NWS and Texel (0.443), respectively. Similar consistency of gametic phase was estimated between NWS and the other NZC populations (∼ 0.52). For all composite sheep populations analyzed in this study, the majority of runs of homozygosity (ROH) segments identified had short length (<2,500 kb), indicating ancient (instead of recent) inbreeding. The variation in the number of ROH segments observed in the NWS was similar to the variation observed in Primera and Lamb Supreme. There was no clear discrimination between NWS and NZC based on the first few principal components. In addition, based on admixture analyses, there seems to be a significant overlap of the ancestral populations that contributed to the development of both NWS and NZC. There were no evident signatures of selection in these populations, which might be due to recent crossbreeding. In conclusion, the NWS composite breed was shown to be moderately related to NZC populations, especially Primera and Lamb Supreme. The findings reported here indicate a promising opportunity for collaborative genomic analyses involving NWS and NZC sheep populations.

Application of Low Coverage Genotyping by Sequencing in Selectively Bred Arctic Charr (Salvelinus alpinus).

Arctic charr (Salvelinus alpinus) is a species of high economic value for the aquaculture industry, and of high ecological value due to its Holarctic distribution in both marine and freshwater environments. Novel genome sequencing approaches enable the study of population and quantitative genetic parameters even on species with limited or no prior genomic resources. Low coverage genotyping by sequencing (GBS) was applied in a selected strain of Arctic charr in Sweden originating from a landlocked freshwater population. For the needs of the current study, animals from year classes 2013 (171 animals, parental population) and 2017 (759 animals; 13 full sib families) were used as a template for identifying genome wide single nucleotide polymorphisms (SNPs). GBS libraries were constructed using the PstI and MspI restriction enzymes. Approximately 14.5K SNPs passed quality control and were used for estimating a genomic relationship matrix. Thereafter a wide range of analyses were conducted in order to gain insights regarding genetic diversity and investigate the efficiency of the genomic information for parentage assignment and breeding value estimation. Heterozygosity estimates for both year classes suggested a slight excess of heterozygotes. Furthermore, FST estimates among the families of year class 2017 ranged between 0.009 - 0.066. Principal components analysis (PCA) and discriminant analysis of principal components (DAPC) were applied aiming to identify the existence of genetic clusters among the studied population. Results obtained were in accordance with pedigree records allowing the identification of individual families. Additionally, DNA parentage verification was performed, with results in accordance with the pedigree records with the exception of a putative dam where full sib genotypes suggested a potential recording error. Breeding value estimation for juvenile growth through the usage of the estimated genomic relationship matrix clearly outperformed the pedigree equivalent in terms of prediction accuracy (0.51 opposed to 0.31). Overall, low coverage GBS has proven to be a cost-effective genotyping platform that is expected to boost the selection efficiency of the Arctic charr breeding program.

Exclusion and Genomic Relatedness Methods for Assignment of Parentage Using Genotyping-by-Sequencing Data.

Genotypes are often used to assign parentage in agricultural and ecological settings. Sequencing can be used to obtain genotypes but does not provide unambiguous genotype calls, especially when sequencing depth is low in order to reduce costs. In that case, standard parentage analysis methods no longer apply. A strategy for using low-depth sequencing data for parentage assignment is developed here. It entails the use of relatedness estimates along with a metric termed excess mismatch rate which, for parent-offspring pairs or trios, is the difference between the observed mismatch rate and the rate expected under a model of inheritance and allele reads without error. When more than one putative parent has similar statistics, bootstrapping can provide a measure of the relatedness similarity. Putative parent-offspring trios can be further checked for consistency by comparing the offspring's estimated inbreeding to half the parent relatedness. Suitable thresholds are required for each metric. These methods were applied to a deer breeding operation consisting of two herds of different breeds. Relatedness estimates were more in line with expectation when the herds were analyzed separately than when combined, although this did not alter which parents were the best matches with each offspring. Parentage results were largely consistent with those based on a microsatellite parentage panel with three discordant parent assignments out of 1561. Two models are investigated to allow the parentage metrics to be calculated with non-random selection of alleles. The tools and strategies given here allow parentage to be assigned from low-depth sequencing data.

Applications of the Soil, Plant and Rumen Microbiomes in Pastoral Agriculture.

The production of dairy, meat, and fiber by ruminant animals relies on the biological processes occurring in soils, forage plants, and the animals' rumens. Each of these components has an associated microbiome, and these have traditionally been viewed as distinct ecosystems. However, these microbiomes operate under similar ecological principles and are connected via water, energy flows, and the carbon and nitrogen nutrient cycles. Here, we summarize the microbiome research that has been done in each of these three environments (soils, forage plants, animals' rumen) and investigate what additional benefits may be possible through understanding the interactions between the various microbiomes. The challenge for future research is to enhance microbiome function by appropriate matching of plant and animal genotypes with the environment to improve the output and environmental sustainability of pastoral agriculture.

Developing Successful Breeding Programs for New Zealand Aquaculture: A Perspective on Progress and Future Genomic Opportunities.

Over the past 40 years New Zealand (NZ) aquaculture has grown into a significant primary industry. Tonnage is small on a global scale, but the industry has built an international reputation for the supply of high quality seafood to many overseas markets. Since the early 1990s the industry has recognized the potential gains from selective breeding and the challenge has been to develop programs that can overcome biological obstacles (such as larval rearing and mortality) and operate cost-effectively on a relatively small scale while still providing significant gains in multiple traits of economic value. This paper provides an overview of the current status, and a perspective on genomic technology implementation, for the family based genetic improvement programs established for the two main species farmed in NZ: Chinook (king) salmon (Oncorhynchus tshawytscha) and GreenshellTM mussel (Perna canaliculus). These programs have provided significant benefit to the industry in which we are now developing genomic resources based on genotyping-by-sequencing to complement the breeding programs, enable evaluation of the genetic diversity and identify the potential benefits of genomic selection. This represents an opportunity to increase genetic gain and more effectively utilize the potential for within family selection.

Reduced representation sequencing detects only subtle regional structure in a heavily exploited and rapidly recolonizing marine mammal species.

Next-generation reduced representation sequencing (RRS) approaches show great potential for resolving the structure of wild populations. However, the population structure of species that have shown rapid demographic recovery following severe population bottlenecks may still prove difficult to resolve due to high gene flow between subpopulations. Here, we tested the effectiveness of the RRS method Genotyping-By-Sequencing (GBS) for describing the population structure of the New Zealand fur seal (NZFS, Arctocephalus forsteri), a species that was heavily exploited by the 19th century commercial sealing industry and has since rapidly recolonized most of its former range from a few isolated colonies. Using 26,026 neutral single nucleotide polymorphisms (SNPs), we assessed genetic variation within and between NZFS colonies. We identified low levels of population differentiation across the species range (<1% of variation explained by regional differences) suggesting a state of near panmixia. Nonetheless, we observed subtle population substructure between West Coast and Southern East Coast colonies and a weak, but significant (p = 0.01), isolation-by-distance pattern among the eight colonies studied. Furthermore, our demographic reconstructions supported severe bottlenecks with potential 10-fold and 250-fold declines in response to Polynesian and European hunting, respectively. Finally, we were able to assign individuals treated as unknowns to their regions of origin with high confidence (96%) using our SNP data. Our results indicate that while it may be difficult to detect population structure in species that have experienced rapid recovery, next-generation markers and methods are powerful tools for resolving fine-scale structure and informing conservation and management efforts.

Genome-wide association study of lung lesions and pleurisy in New Zealand lambs.

Pneumonia is an important issue for sheep production, leading to reduced growth rate and a predisposition to pleurisy. The objective of this study was to identify loci associated with pneumonic lesions and pleurisy in New Zealand progeny test lambs. The lungs from 3,572 progeny-test lambs were scored for presence and severity of pneumonic lesions and pleurisy at slaughter. Animals were genotyped using the Illumina Ovine Infinium HD SNP BeadChip (606,006 markers). The heritability of lung lesion score and pleurisy were calculated using the genomic relationship matrix, and genome-wide association analyses were conducted using EMMAX and haplotype trend regression. At slaughter, 35% of lambs had pneumonic lesions, with 9% showing lesions on more than half of any individual lobe. The number of lambs recorded as having pleurisy by the processing plants was 9%. Heritability estimates for pneumonic lesions and pleurisy scores adjusted for heteroscedasticity (CPSa and PLEURa) were 0.16 (± 0.03) and 0.05 (± 0.02), respectively. Five single-nucleotide polymorphisms (SNPs) were significantly associated with pneumonic lesions at the genome-wide level, and additional 37 SNPs were suggestively significant. Four SNPs were significantly associated with pleurisy, with an additional 11 SNPs reaching the suggestive level of significance. There were no regions that overlapped between the 2 traits. Multiple SNPs were in regions that contained genes involved in either the DNA damage response or the innate immune response, including several that had previously been reported to have associations with respiratory disease. Both EMMAX and HTR analyses of pleurisy data showed a significant peak on chromosome 2, located downstream from the transcription factor SP3. SP3 activates or suppresses the expression of numerous genes, including several genes with known functions in the immune system. This study identified several SNPs associated with genes involved in both the innate immune response and the response to DNA damage that are associated with pneumonic lesions and pleurisy in lambs at slaughter. Additionally, the identification in sheep of several SNPs within genes that have previously been associated with the respiratory system in cattle, pigs, rats, and mice indicates that there may be common pathways that underlie the response to invasion by respiratory pathogens in multiple species.