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Aleutian disease (AD) brings tremendous financial losses to the mink industry. Selecting AD-resilient mink has been conducted to control AD. Such selections could have altered the patterns of genetic variation responding to selection pressures. This study aimed to identify selection signatures for immune response (IRE) and resilience to AD. A total of 1,411 mink froman AD-positive facilitywere used. For IRE, 264 animals were categorized according to the combined results of enzyme-linked immunosorbent assay (ELISA) and counterimmunoelectrophoresis (CIEP). For resilience, two grouping methods were used: 1) general resilience performance (GRP, n = 30) was evaluated based on the feed conversion ratio, Kleiber ratio, and pelt quality; and 2) female reproductive performance (FRP, n = 36) wasmeasured based on the number of kits alive 24 h after birth. Detectionmethods were the pairwise fixation index, nucleotide diversity, and cross-population extended haplotype homozygosity. A total of 619, 569, and 526 SNPs were identified as candidates for IRE, GRP, and FRP, respectively. The annotated geneswere involved in immune system process, growth, reproduction, and pigmentation. Two olfactoryrelated Gene Ontology (GO) terms were significant (q < 0.05) for all traits, suggesting the impact of AD on the sense of smell of infected mink. Differences in detected genes and GO terms among different color types for IRE indicated variations in immune response to AD among color types. The mitogen-activated protein kinase (MAPK) signaling pathway was significant (q < 0.05) for FRP, suggesting that AD may disrupt MAPK signaling and affect FRP. The findings of this research contribute to our knowledge of the genomic architecture and biological mechanisms underlying AD resilience in mink. [ABSTRACT FROM AUTHOR]

Zoonotic transmission of H5N1 highly pathogenic avian influenza virus (HPAIV) into the human population is an increasing global threat. The recent 2022 HPAIV outbreak significantly highlighted this possibility, increasing concern in the general population. The clinical outcomes of H5N1 influenza virus exposure can be determined by an individual’s primary influenza virus infection (imprinting) or vaccination status. Immunological imprinting with Group 1 - (H1N1, H2N2, and H2N3) increases survival rates following H5N1 viral infection compared to Group 2 - (H3N2) imprinted individuals. Vaccination against H5N1 influenza viruses can offer protection to at-risk populations; however, stockpiled inactivated H5N1 influenza vaccines are not readily available to the public. We hypothesize that the immunological response to vaccination and subsequent clinical outcome following H5N1 influenza virus infection is correlated with the immunological imprinting status of an individual. To test this hypothesis, our lab established a ferret pre-immune model of disease. Naïve ferrets were intranasally inoculated with seasonal influenza viruses and allowed to recover for 84  days prior to H5N1 virus infection. Ferrets imprinted following H1N1 and H2N3 virus infections were completely protected against lethal H5N1 influenza virus challenge (100% survival), with few to no clinical symptoms. In comparison, H3N2 influenza virus)imprinted ferrets had severe clinical symptoms, delayed disease progression, and a sublethal phenotype (40% mortality). Consecutive infections with H1N1 influenza viruses followed by an H3N2 influenza virus infection did not abrogate the immune protection induced by the original H1N1 influenza virus infection. In addition, ferrets consecutively infected with H1N1 and H2N3 viruses had no clinical symptoms or weight loss. H3N2 pre-immune ferrets were vaccinated with a broadly reactive H5 HA-based or H1 NA-based vaccine (Hu-CO 2). These ferrets were protected against H5N1 influenza virus challenge, whereas ferrets vaccinated with the H1N1 wild-type CA/09 rHA vaccine had similar phenotypes as non-vaccinated H3N2-imprinted ferrets with 40% survival. Overall, Group 2 imprinted ferrets, which were vaccinated with heterologous Group 1 HA vaccines, had redirected immune responses to Group 1 influenza viral antigens and rescued a sublethal phenotype to complete protection. [ABSTRACT FROM AUTHOR]

Understanding the genetic structure of the target population is critically important to develop an efficient genomic selection program in domestic animals. In this study, 2,973 American mink of six color types from two farms (Canadian Centre for Fur Animal Research (CCFAR), Truro, NS and Millbank Fur Farm (MFF), Rockwood, ON) were genotyped with the Affymetrix Mink 70K panel to compute their linkage disequilibrium (LD) patterns, effective population size (Ne), genetic diversity, genetic distances, and population differentiation and structure. The LD pattern represented by average r², decreased to <0.2 when the inter-marker interval reached larger than 350 kb and 650 kb for CCFAR and MFF, respectively, and suggested at least 7,700 and 4,200 single nucleotide polymorphisms (SNPs) be used to obtain adequate accuracy for genomic selection programs in CCFAR and MFF respectively. The Ne for five generations ago was estimated to be 76 and 91 respectively. Our results from genetic distance and diversity analyses showed that American mink of the various color types had a close genetic relationship and low genetic diversity, with most of the genetic variation occurring within rather than between color types. Three ancestral genetic groups was considered the most appropriate number to delineate the genetic structure of these populations. Black (in both CCFAR and MFF) and pastel color types had their own ancestral clusters, while demi, mahogany, and stardust color types were admixed with the three ancestral genetic groups. This study provided essential information to utilize the first medium-density SNP panel for American mink in their genomic studies. [ABSTRACT FROM AUTHOR]

Aleutian disease (AD) is a severe health issue for the mink industry, causing increased mortality and adversely impacting several economically important traits, resulting in substantial economic losses. AD has been characterized as an immune complex disease, which indicates that the greater concentrations of antiAMDV antibodies produced more harmful to the host. Resilience is defined as the ability the animals have to maintain their performance under exposure to diseasecausing agents and disruptions. The phenotypic selection of AD-resilient mink based on immune response and/or indicator traits is practiced by some mink farms, but the genetic architecture of immune response and resilience to AD has not been widely explored. In this study, mink (n = 1,411) from the Canadian Centre for Fur Animal Research (Truro, Nova Scotia, Canada), which is an AD-positive facility, were used to detect potential genomic regions and genes related to immune response and feed-intake-related resilience of mink to AD through genome-wide association studies (GWAS) analyses. The studied individuals were genotyped using the Axiom Affymetrix Mink 70K single nucleotide polymorphism (SNP) panel. The studied phenotypes included two immune response traits measured by antigen-based enzyme-linked immunosorbent assay (ELISA-G) and iodine agglutination test (IAT) and two feed-intake-related resilience traits measured by the daily variation in feed intake (Varf) and proportion of off-feed d (DOF). The de-regressed breeding values were derived from the estimated breeding values for each trait and utilized as pseudo-phenotypes to perform GWAS analyses using a single SNP univariate mixed linear animal model in SNP1101 software. A total of 17 significant [false-discovery-rate-adjusted-pvalue (q) < 0.01] SNPs were detected to be associated with ELISA-G, and 141 genes were annotated from the detected SNPs. Among all the annotated genes, three genes, MPIG6B, RUNX2, and C4A, were found to have important roles in immune-mediated responses to AD. Eight SNPs were detected to be significantly associated with IAT, and 44 genes were annotated from these eight SNPs. Two (TNFRSF11A and C4A) of the 44 genes were involved in the immune system process. For DOF, seven significant associated SNPs were detected, and 42 genes were annotated from these SNPs. Two annotated genes, ADCY7 and CNDP2, were related to feed intake or appetite. Five significant (q < 0.05) overrepresented gene ontology enrichment terms, including TAP complex, Classical-complementpathway C3/C5 convertase complex, MHC class I peptide loading complex, extracellular region, and ABC-type peptide transporter activity, were detected for ELISA-G, and they have important roles in the adaptive immune response or complement system. The newly detected significant SNPs and identified candidate genes in this study would provide a better understanding of the genetic architecture and biological mechanisms underlying AD resilience in mink, which offers an opportunity for increasing the resilience of mink to AD using marker-assisted/genomic selection in mink. [ABSTRACT FROM AUTHOR]