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.

• Klíčová slova
• Association, Horse, KLRA, MHC, Sarcoid,
• MeSH
• genetická predispozice k nemoci * MeSH
• genotyp MeSH
• geny MHC třídy I * genetika   MeSH
• geny MHC třídy II * genetika   MeSH
• koně MeSH
• MHC antigeny II. třídy genetika   MeSH
• mikrosatelitní repetice genetika   MeSH
• nemoci koní * genetika   imunologie   MeSH
• sarkoidóza * veterinární   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• MHC antigeny II. třídy MeSH

Toll-like receptors (TLRs) represent an important part of the innate immune system. While human and murine TLRs have been intensively studied, little is known about TLRs in non-model species. The order Perissodactyla comprises a variety of free-living and domesticated species exposed to different pathogens in different habitats and is therefore suitable for analyzing the diversity and evolution of immunity-related genes. We analyzed TLR genes in the order Perissodactyla with a focus on the family Equidae. Twelve TLRs were identified by bioinformatic analyses of online genomic resources; their sequences were confirmed in equids by genomic DNA re-sequencing of a panel of nine species. The expression of TLR11 and TLR12 was confirmed in the domestic horse by cDNA sequencing. Phylogenetic reconstruction of the TLR gene family in Perissodactyla identified six sub-families. TLR4 clustered together with TLR5; the TLR1-6-10 subfamily showed a high degree of sequence identity. The average estimated evolutionary divergence of all twelve TLRs studied was 0.3% among the Equidae; the most divergent CDS were those of Equus caballus and Equus hemionus kulan (1.34%) in the TLR3, and Equus africanus somaliensis and Equus quagga antiquorum (2.1%) in the TLR1 protein. In each TLR gene, there were haplotypes shared between equid species, most extensively in TLR3 and TLR9 CDS, and TLR6 amino acid sequence. All twelve TLR genes were under strong negative overall selection. Signatures of diversifying selection in specific codon sites were detected in all TLRs except TLR8. Differences in the selection patterns between virus-sensing and non-viral TLRs were observed.

• Klíčová slova
• Equid, Innate immunity, Odd-toe ungulates, Toll-like receptor, Transpecies haplotype sharing,
• MeSH
• Equidae MeSH
• fylogeneze MeSH
• genomika MeSH
• koně genetika   MeSH
• lidé MeSH
• myši MeSH
• Perissodactyla metabolismus   MeSH
• toll-like receptor 1 * genetika   MeSH
• toll-like receptor 3 * MeSH
• toll-like receptory genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• toll-like receptor 1 * MeSH
• toll-like receptor 3 * MeSH
• toll-like receptory MeSH

BACKGROUND: The mammalian Major Histocompatibility Complex (MHC) is a genetic region containing highly polymorphic genes with immunological functions. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. The MHC class II sub-region contains genes expressed in antigen presenting cells. The antigen binding site is encoded by the second exon of genes encoding antigen presenting molecules. The exon 2 sequences of these MHC genes have evolved under the selective pressure of pathogens. Interspecific differences can be observed in the class II sub-region. The family Equidae includes a variety of domesticated, and free-ranging species inhabiting a range of habitats exposed to different pathogens and represents a model for studying this important part of the immunogenome. While equine MHC class II DRA and DQA loci have received attention, the genetic diversity and effects of selection on DRB and DQB loci have been largely overlooked. This study aimed to provide the first in-depth analysis of the MHC class II DRB and DQB loci in the Equidae family. RESULTS: Three DRB and two DQB genes were identified in the genomes of all equids. The genes DRB2, DRB3 and DQB3 showed high sequence conservation, while polymorphisms were more frequent at DRB1 and DQB1 across all species analyzed. DQB2 was not found in the genome of the Asiatic asses Equus hemionus kulan and E. h. onager. The bioinformatic analysis of non-zero-coverage-bases of DRB and DQB genes in 14 equine individual genomes revealed differences among individual genes. Evidence for recombination was found for DRB1, DRB2, DQB1 and DQB2 genes. Trans-species allele sharing was identified in all genes except DRB1. Site-specific selection analysis predicted genes evolving under positive selection both at DRB and DQB loci. No selected amino acid sites were identified in DQB3. CONCLUSIONS: The organization of the MHC class II sub-region of equids is similar across all species of the family. Genomic sequences, along with phylogenetic trees suggesting effects of selection as well as trans-species polymorphism support the contention that pathogen-driven positive selection has shaped the MHC class II DRB/DQB sub-regions in the Equidae.

• Klíčová slova
• Family Equidae, MHC class II loci, MHC exon 2, Major histocompatibility complex, Positive selection, Selected amino acid sites, Trans-species polymorphism,
• MeSH
• Equidae klasifikace   genetika   MeSH
• fylogeneze MeSH
• hlavní histokompatibilní komplex genetika   MeSH
• molekulární evoluce * MeSH
• polymorfismus genetický * MeSH
• rekombinace genetická MeSH
• selekce (genetika) * MeSH
• vznik druhů (genetika) MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Immunity exhibits extraordinarily high levels of variation. Evolution of the immune system in response to host-pathogen interactions in particular ecological contexts appears to be frequently associated with diversifying selection increasing the genetic variability. Many studies have documented that immunologically relevant polymorphism observed today may be tens of millions years old and may predate the emergence of present species. This pattern can be explained by the concept of trans-species polymorphism (TSP) predicting the maintenance and sharing of favourable functionally important alleles of immune-related genes between species due to ongoing balancing selection. Despite the generality of this concept explaining the long-lasting adaptive variation inherited from ancestors, current research in TSP has vastly focused only on major histocompatibility complex (MHC). In this review we summarise the evidence available on TSP in human and animal immune genes to reveal that TSP is not a MHC-specific evolutionary pattern. Further research should clearly pay more attention to the investigation of TSP in innate immune genes and especially pattern recognition receptors which are promising candidates for this type of evolution. More effort should also be made to distinguish TSP from convergent evolution and adaptive introgression. Identification of balanced TSP variants may represent an accurate approach in evolutionary medicine to recognise disease-resistance alleles.

• MeSH
• alely MeSH
• hlavní histokompatibilní komplex genetika   imunologie   MeSH
• interakce hostitele a patogenu genetika   imunologie   MeSH
• lidé MeSH
• molekulární evoluce MeSH
• polymorfismus genetický genetika   imunologie   MeSH
• přirozená imunita genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Natural killer (NK) cells have important functions in immunity. NK recognition in mammals can be mediated through killer cell immunoglobulin-like receptors (KIR) and/or killer cell lectin-like Ly49 receptors. Genes encoding highly variable NK cell receptors (NKR) represent rapidly evolving genomic regions. No single conservative model of NKR genes was observed in mammals. Single-copy low polymorphic NKR genes present in one mammalian species may expand into highly polymorphic multigene families in other species. In contrast to other non-rodent mammals, multiple Ly49-like genes appear to exist in the horse, while no functional KIR genes were observed in this species. In this study, Ly49 and KIR were sought and their evolution was characterized in the entire family Equidae. Genomic sequences retrieved showed the presence of at least five highly conserved polymorphic Ly49 genes in horses, asses and zebras. These findings confirmed that the expansion of Ly49 occurred in the entire family. Several KIR-like sequences were also identified in the genome of Equids. Besides a previously identified non-functional KIR-Immunoglobulin-like transcript fusion gene (KIR-ILTA) and two putative pseudogenes, a KIR3DL-like sequence was analyzed. In contrast to previous observations made in the horse, the KIR3DL sequence, genomic organization and mRNA expression suggest that all Equids might produce a functional KIR receptor protein molecule with a single non-mutated immune tyrosine-based inhibition motif (ITIM) domain. No evidence for positive selection in the KIR3DL gene was found. Phylogenetic analysis including rhinoceros and tapir genomic DNA and deduced amino acid KIR-related sequences showed differences between families and even between species within the order Perissodactyla. The results suggest that the order Perissodactyla and its family Equidae with expanded Ly49 genes and with a potentially functional KIR gene may represent an interesting model for evolutionary biology of NKR genes.

• MeSH
• frekvence genu genetika   MeSH
• fúze genů MeSH
• fylogeneze MeSH
• genom genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• koně genetika   MeSH
• lektinové receptory NK-buněk - podrodina A genetika   MeSH
• molekulární sekvence - údaje MeSH
• počítačová simulace MeSH
• receptory buněk NK chemie   genetika   metabolismus   MeSH
• savčí chromozomy genetika   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie aminokyselin MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lektinové receptory NK-buněk - podrodina A MeSH
• receptory buněk NK MeSH

Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses caused by bites of insects. IBH is a multifactorial disease with contribution of genetic and environmental factors. Candidate gene association analysis of IBH was performed in a group of 89 Icelandic horses all born in Iceland and imported to Europe. Horses were classified in IBH-affected and non-affected based on clinical signs and history of recurrent dermatitis, and on the results of an in vitro sulfidoleukotriene (sLT)-release assay with Culicoides nubeculosus and Simulium vittatum extract. Different genetic markers were tested for association with IBH by the Fisher's exact test. The effect of the major histocompatibility complex (MHC) gene region was studied by genotyping five microsatellites spanning the MHC region (COR112, COR113, COR114, UM011 and UMN-JH34-2), and exon 2 polymorphisms of the class II Eqca-DRA gene. Associations with Eqca-DRA and COR113 were identified (p < 0.05). In addition, a panel of 20 single nucleotide polymorphisms (SNPs) in 17 candidate allergy-related genes was tested. During the initial screen, no marker from the panel was significantly (p < 0.05) associated with IBH. Five SNPs associated with IBH at p < 0.10 were therefore used for analysis of combined genotypes. Out of them, SNPs located in the genes coding for the CD14 receptor (CD14), interleukin 23 receptor (IL23R), thymic stromal lymphopoietin (TSLP) and transforming growth factor beta 3 (TGFB3) molecules were associated with IBH as parts of complex genotypes. These results are supported by similar associations and by expression data from different horse populations and from human studies.

• MeSH
• alergie genetika   imunologie   veterinární   MeSH
• Ceratopogonidae imunologie   patogenita   MeSH
• dermatitida genetika   veterinární   MeSH
• hlavní histokompatibilní komplex genetika   MeSH
• koně genetika   imunologie   MeSH
• kousnutí a bodnutí hmyzem genetika   imunologie   MeSH
• Simuliidae imunologie   patogenita   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Island MeSH