Most cited article - PubMed ID 31005660
Genetic susceptibility to West Nile virus infection in Camargue horses
Although the Major Histocompatibility Complex (MHC) has been repeatedly associated with susceptibility to equine sarcoid, a disease associated with bovine papillomavirus infection, the role of the MHC in the mechanisms of the disease is not fully understood. The objectives of our work were to analyze associations between polymorphic markers of the MHC genomic subregions and of the Natural Killer Complex (NKC) genomic region and the presence of sarcoid in Arabian horses. Microsatellite loci located in the MHC class I, II and III subregions and two MHC class II genes (DRA, DQA1), along with a set of NKC (KLRA, CLEC subregions) microsatelllite markers were genotyped. Fifteen microsatellites of the standard parentage kit, located outside the MHC and NKC regions, were tested as controls. Standard chi-square and Fisher tests with Bonferroni corrections were used for association analyses. Significant associations of MHC class II and MHC class I_KLRA polymorphic markers with the presence of clinical sarcoid were observed. These findings are consistent with biological theory and indicate a role of MHC class I, class II and KLRA molecules in adaptive as well as in innate immune responses to equine sarcoid. Although limited to Arabian horses, these data point to an as yet unadressed hypothesis regarding the possible roles of NK cells in the pathogenesis of equine sarcoid.
- Keywords
- Association, Horse, KLRA, MHC, Sarcoid,
- MeSH
- Genetic Predisposition to Disease * MeSH
- Genotype MeSH
- Genes, MHC Class I * genetics MeSH
- Genes, MHC Class II * genetics MeSH
- Horses MeSH
- Histocompatibility Antigens Class II genetics MeSH
- Microsatellite Repeats genetics MeSH
- Horse Diseases * genetics immunology MeSH
- Sarcoidosis * veterinary genetics immunology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Histocompatibility Antigens Class II MeSH
Toll-like receptors (TLRs) play important roles in innate immunity and developmental processes. Due to their nature as molecular pattern recognition receptors, their genetic diversity may reflect the effects of various pathogen pressures. Here, the extent of variability in the TLR1-6-10 gene cluster in three geographically and historically distinct breeds of horses was analysed. A genetically diverse group of representatives of 14 other horse breeds provided additional information on the variability of this gene cluster in the domestic horse. Altogether, 25 SNPs were identified in the TLR6-1-10 gene cluster across the 4 equine breed groups studied, of which 7 were synonymous and 18 non-synonymous. Twenty-eight inferred SNPs and 22 in silico translated amino acid haplotypes were identified. A predominant major haplotype present in all breed groups along with several group-specific haplotypes were identified. Strong linkage disequilibrium was detected for several SNPs, as well as effects of pervasive, site-specific selection. The existence of a major haplotype suggests it may confer a selective advantage across breeds. Less frequent breed-specific haplotypes may represent variability required or beneficial for responses to local pathogen pressures. Purifying site-specific selection was detected in the TIR domain and its vicinity in TLR6, whereas AA sites under diversifying selection were located in LRR domains and/or their surroundings in TLR1. Population structure models based on immune-related TLR6-1-10 markers did not distinguish between breed groups, whereas in models based on neutral microsatellite markers, breed groups clustered separately. This supports the assumption that the diversity of the TLR6-1-10 cluster is of adaptive value. The TLR6-1-10 alleles and haplotypes identified represent potential candidate markers for disease association studies.
- Keywords
- equine, haplotype, innate immunity, toll‐like receptor,
- MeSH
- Genetic Variation * MeSH
- Haplotypes MeSH
- Polymorphism, Single Nucleotide MeSH
- Horses genetics immunology MeSH
- Multigene Family MeSH
- Immunity, Innate * genetics MeSH
- Toll-Like Receptor 6 * genetics MeSH
- Toll-Like Receptors * genetics metabolism MeSH
- Linkage Disequilibrium MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Toll-Like Receptor 6 * MeSH
- Toll-Like Receptors * MeSH
The Feline coronavirus (FCoV) can cause a fatal disease, the Feline Infectious Peritonitis. Persistent shedders represent the most important source of infection. The role of the host in FCoV fecal shedding is unknown. The objective of this study was to develop gene markers and to test their associations with FCoV shedding patterns. Fecal samples were taken from 57 cats of 12 breeds on the day 0 and after 2, 4 and 12 months. Variation from persistent and/or high-intensity shedding to no shedding was observed. Thirteen immunity-related genes were selected as functional and positional/functional candidates. Positional candidates were selected in a candidate region detected by a GWAS analysis. Tens to hundreds of single nucleotide polymorphisms (SNPs) per gene were identified using next generation sequencing. Associations with different phenotypes were assessed by chi-square and Fisher's exact tests. SNPs of one functional and one positional candidate (NCR1 and SLX4IP, respectively) and haplotypes of four genes (SNX5, NCR2, SLX4IP, NCR1) were associated with FCoV shedding at pcorected < 0.01. Highly significant associations were observed for extreme phenotypes (persistent/high-intensity shedders and non-shedders) suggesting that there are two major phenotypes associated with different genotypes, highly susceptible cats permanently shedding high amounts of viral particles and resistant non-shedders.
The West Nile virus (WNV) is a mosquito-borne flavivirus causing meningoencephalitis in humans and animals. Due to their particular susceptibility to WNV infection, horses serve as a sentinel species. In a population of Romanian semi-feral horses living in the Danube delta region, we have analyzed the distribution of candidate polymorphic genetic markers between anti WNV-IgG seropositive and seronegative horses. Thirty-six SNPs located in 28 immunity-related genes and 26 microsatellites located in the MHC and LY49 complex genomic regions were genotyped in 57 seropositive and 32 seronegative horses. The most significant association (pcorr < 0.0002) was found for genotypes composed of markers of the SLC11A1 and TLR4 genes. Markers of five other candidate genes (ADAM17, CXCR3, IL12A, MAVS, TNFA), along with 5 MHC class I and LY49-linked microsatellites were also associated with the WNV antibody status in this model horse population. The OAS1 gene, previously associated with WNV-induced clinical disease, was not associated with the presence of anti-WNV antibodies.
- Keywords
- Horse, MHC, Microsatellite, NKR, Polymorphism, Restriction fragment length polymorphism, SLC11A1, TLR4, West Nile virus,
- MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Polymorphism, Single Nucleotide genetics MeSH
- Horses blood genetics immunology MeSH
- Microsatellite Repeats genetics MeSH
- Polymorphism, Restriction Fragment Length MeSH
- Antibodies, Viral analysis blood MeSH
- Sentinel Species MeSH
- West Nile virus pathogenicity MeSH
- West Nile Fever genetics immunology veterinary MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Romania MeSH
- Names of Substances
- Antibodies, Viral MeSH
