Polymorphism of the major histocompatibility complex (MHC), DAB1 gene was characterized for the first time in the European bitterling (Rhodeus amarus), a freshwater fish employed in studies of host-parasite coevolution and mate choice, taking advantage of newly designed primers coupled with high-throughput amplicon sequencing. Across 221 genotyped individuals, we detected 1-4 variants per fish, with 28% individuals possessing 3-4 variants. We identified 36 DAB1 variants, and they showed high sequence diversity mostly located within predicted antigen-binding sites, and both global and codon-specific excess of non-synonymous mutations. Despite deep divergence between two major allelic lineages, functional diversity was surprisingly low (3 supertypes). Overall, these findings suggest the role of positive and balancing selection in promotion and long-time maintenance of DAB1 polymorphism. Further investigations will clarify the role of pathogen-mediated selection to drive the evolution of DAB1 variation.

• Klíčová slova
• Gene duplication, MHC class IIB, MHC supertypes, Positive selection, Positively selected sites, Rhodeus amarus,
• MeSH
• alely MeSH
• Cyprinidae * genetika   parazitologie   MeSH
• fylogeneze MeSH
• genetická variace MeSH
• geny MHC třídy II MeSH
• hlavní histokompatibilní komplex MeSH
• molekulární evoluce MeSH
• selekce (genetika) MeSH
• variabilita počtu kopií segmentů DNA * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The CD94 receptor, expressed on natural killer (NK) and CD8+ T cells, is known as a relatively non-polymorphic receptor with orthologues in humans, other primates, cattle, and rodents. In the house mouse (Mus musculus), a single allele is highly conserved among laboratory strains, and reports of allelic variation in lab- or wild-living mice are lacking, except for deficiency in one lab strain (DBA/2J). The non-classical MHC-I molecule Qa-1b is the ligand for mouse CD94/NKG2A, presenting alternative non-americ fragment of leader peptides (Qa-1 determinant modifier (Qdm)) from classical MHC-I molecules. Here, we report a novel allele identified in free-living house mice captured in Norway, living among individuals carrying the canonical Cd94 allele. The novel Cd94LocA allele encodes 12 amino acid substitutions in the extracellular lectin-like domain. Flow cytometric analysis of primary NK cells and transfected cells indicates that the substitutions prevent binding of CD94 mAb and Qa-1b/Qdm tetramers. Our data further indicate correlation of Cd94 polymorphism with the two major subspecies of house mice in Europe. Together, these findings suggest that the Cd94LocA/NKG2A heterodimeric receptor is widely expressed among M. musculus subspecies musculus, with ligand-binding properties different from mice of subspecies domesticus, such as the C57BL/6 strain.

• Klíčová slova
• Comparative immunology/evolution, Genomics, Inhibitory/activating receptors, MHC, NK cell,
• MeSH
• alely MeSH
• buňky NK metabolismus   MeSH
• CD8-pozitivní T-lymfocyty metabolismus   MeSH
• CHO buňky MeSH
• Cricetulus MeSH
• druhová specificita MeSH
• HEK293 buňky MeSH
• křečci praví MeSH
• lektinové receptory NK-buněk - podrodina C chemie   genetika   metabolismus   MeSH
• lektinové receptory NK-buněk - podrodina D chemie   genetika   metabolismus   MeSH
• lidé MeSH
• MHC antigeny I. třídy chemie   genetika   metabolismus   MeSH
• multimerizace proteinu MeSH
• myši inbrední C57BL MeSH
• myši inbrední DBA MeSH
• peptidy chemie   genetika   metabolismus   MeSH
• polymorfismus genetický * MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• křečci praví MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Norsko MeSH
• Názvy látek
• lektinové receptory NK-buněk - podrodina C MeSH
• lektinové receptory NK-buněk - podrodina D MeSH
• MHC antigeny I. třídy MeSH
• peptidy MeSH
• Q surface antigens MeSH Prohlížeč
• Qdm protein, mouse MeSH Prohlížeč

Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence identity across the family. Single nucleotide polymorphisms (SNPs) were found in the coding and noncoding regions of the gene. Seven codon sites were identified to be under strong purifying selection. Codons located in three regions, including the glycosylated extracellular loop, were shown to be under diversifying selection. A 3-bp indel resulting in a deletion of the amino acid 321 in the predicted protein was observed in all horses, while it has been maintained in all other equid species. This codon comprised in an N-glycosylation site was found to be under positive selection. Interspecific variation in the presence of predicted N-glycosylation sites was observed.

• Klíčová slova
• Equidae, Polymorphism, SLC11A1 gene,
• MeSH
• Equidae genetika   MeSH
• fylogeneze MeSH
• genomika MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kodon genetika   MeSH
• molekulární evoluce * MeSH
• proteiny přenášející kationty genetika   MeSH
• selekce (genetika) genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kodon MeSH
• natural resistance-associated macrophage protein 1 MeSH Prohlížeč
• proteiny přenášející kationty MeSH

The polymorphism of exon 2 of the DAB genes (major histocompatibility complex [MHC] class IIB) was investigated for the first time in the freshwater cyprinid fish species, Squalius cephalus, in the wide range of its distribution in Europe. We identified 111 different MHC class IIB variants in 15 chub populations distributed from Finland to Spain. The sequence analysis showed that many structurally important amino acid sites that were conserved among tetrapods were also conserved in chub. The analysis of recombination indicated that it does not play an important role in producing and maintaining the variation of DAB genes analyzed in the present study. The exon 2 was shown to be subjected to intense positive selection. Phylogenetic analysis and sequence identities suggest the presence of two class IIB loci (DAB1-like and DAB3-like) in chub. Nevertheless, the presence of three DAB3-like sequence variants in several individuals indicates the duplication of the DAB3 gene. A contrasting selection pattern was found in DAB1-like and DAB3-like genes, which suggests the potential functional differences between these genes. Some DAB sequence variants were shared among the populations of different mtDNA lineages. The phylogenetic analyses did not confirm any biogeographical pattern of the genetic structure of MHC IIB in chub, which is in line with balancing selection and trans-species polymorphism in MHC genes. Nevertheless, cluster analysis based on the presence/absence of DAB sequence variants in the populations showed the phylogeophraphical pattern corresponding to the mtDNA lineages, which indicates that neutral selection can partially explain the MHC IIB evolution in chub.

• MeSH
• Cyprinidae genetika   imunologie   MeSH
• exony MeSH
• geny MHC třídy II * MeSH
• molekulární evoluce * MeSH
• polymorfismus genetický MeSH
• selekce (genetika) MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

Elimination of pathogens is the basis of host resistance to infections; however, relationship between persisting pathogens and disease has not been clarified. Leishmania major infection in mice is an important model of host-pathogen relationship. Infected BALB/c mice exhibit high parasite numbers in lymph nodes and spleens, and a chronic disease with skin lesions, splenomegaly, and hepatomegaly, increased serum IgE levels and cytokine imbalance. Although numerous gene loci affecting these disease symptoms have been reported, genes controlling parasites' elimination or dissemination have never been mapped. We therefore compared genetics of the clinical and immunologic symptomatology with parasite load in (BALB/c x CcS-11) F2 hybrids and mapped five loci, two of which control parasite elimination or dissemination. Lmr5 influences parasite loads in spleens (and skin lesions, splenomegaly, and serum IgE, IL-4, and IFNgamma levels), and Lmr20 determines parasite numbers in draining lymph nodes (and serum levels of IgE and IFNgamma), but no skin or visceral pathology. Three additional loci do not affect parasite numbers but influence significantly the disease phenotype-Lmr21: skin lesions and IFNgamma levels, Lmr22: IL-4 levels, Lmr23: IFNgamma levels, indicating that development of L. major-caused disease includes critical regulations additional to control of parasite spread.

• MeSH
• interferon gama krev   MeSH
• kůže patologie   MeSH
• Leishmania major imunologie   MeSH
• leishmanióza kožní genetika   imunologie   parazitologie   patologie   MeSH
• lymfatické uzliny parazitologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• pohlavní dimorfismus MeSH
• slezina parazitologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• interferon gama MeSH

The major histocompatibility complex genes coding for antigen binding and presenting molecules are the most polymorphic genes in the vertebrate genome. We studied the DRA and DQA gene polymorphism of the family Equidae. In addition to 11 previously reported DRA and 24 DQA alleles, six new DRA sequences and 13 new DQA alleles were identified in the genus Equus. Phylogenetic analysis of both DRA and DQA sequences provided evidence for trans-species polymorphism in the family Equidae. The phylogenetic trees differed from species relationships defined by standard taxonomy of Equidae and from trees based on mitochondrial or neutral gene sequence data. Analysis of selection showed differences between the less variable DRA and more variable DQA genes. DRA alleles were more often shared by more species. The DQA sequences analysed showed strong amongst-species positive selection; the selected amino acid positions mostly corresponded to selected positions in rodent and human DQA genes.

• MeSH
• alely MeSH
• DNA primery genetika   MeSH
• DNA genetika   MeSH
• druhová specificita MeSH
• Equidae klasifikace   genetika   imunologie   MeSH
• fylogeneze MeSH
• genetická variace MeSH
• hlavní histokompatibilní komplex * MeSH
• imunogenetické jevy MeSH
• koně genetika   imunologie   MeSH
• molekulární evoluce MeSH
• molekulární sekvence - údaje MeSH
• polymorfismus genetický * MeSH
• polymorfismus konformace jednovláknové DNA MeSH
• sekvence nukleotidů MeSH
• sekvenční homologie nukleových kyselin MeSH
• selekce (genetika) * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• DNA primery MeSH
• DNA MeSH

Although the number of studies focusing on the major histocompatibility complex (MHC) in non-model vertebrates is increasing, results are often contradictory, and the structure of MHC is still poorly understood in wild species. Here, we describe the structure and diversity of exon 3 of MHC class I in a passerine bird, the Scarlet Rosefinch (Carpodacus erythrinus). Using capillary electrophoresis single-strand conformation polymorphism, we identified 82 different MHC class I variants in one Rosefinch population nesting at one site in the Czech Republic. Thus far, this is the highest intra-populational MHC class I variation observed in birds. We have not found support for 'minimal essential' MHC in this species since individuals exhibited between three and nine different exon 3 sequences, indicating that there may be at least five amplified MHC class I genes. By cloning, we obtained and analysed 29 exon sequences and found that all of them could be translated into potentially functional proteins. We also show that strong positive selection appears to be acting mainly, but not only, on previously described antigen-binding sites in MHC class I genes. Furthermore, our results indicate that recombination has played an important role in generating genetic diversity of these genes in the Scarlet Rosefinch; we discuss the significance of this extremely high genetic diversity in light of the life history traits of this species, such as long-distance migration.

• MeSH
• genetická variace * MeSH
• MHC antigeny I. třídy genetika   MeSH
• migrace zvířat MeSH
• molekulární evoluce MeSH
• molekulární sekvence - údaje MeSH
• Passeriformes klasifikace   genetika   imunologie   MeSH
• polymorfismus konformace jednovláknové DNA MeSH
• populační genetika MeSH
• rekombinace genetická MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční homologie nukleových kyselin MeSH
• vazebná nerovnováha MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• MHC antigeny I. třídy MeSH

Atopy is a predisposition to hyperproduction of immunoglobulin E (IgE) against common environmental allergens. It is often associated with development of allergic diseases such as asthma, rhinitis, and dermatitis. Production of IgE is influenced by genetic and environmental factors. In spite of progress in the study of heredity of atopy, the genetic mechanisms of IgE regulation have not yet been completely elucidated. The analysis of complex traits can benefit considerably from integration of human and mouse genetics. Previously, we mapped a mouse IgE-controlling locus Lmr9 on chromosome 4 to a segment of <9 Mb. In this study, we tested levels of total IgE and 25 specific IgEs against inhalant and food allergens in 67 Czech atopic families. In the position homologous to Lmr9 on chromosome 8q12 marked by D8S285, we demonstrated a novel human IgE-controlling locus exhibiting suggestive linkage to composite inhalant allergic sensitization (limit of detection, LOD = 2.11, P = 0.0009) and to nine specific IgEs, with maximum LOD (LOD = 2.42, P = 0.0004) to plantain. We also tested 16 markers at previously reported chromosomal regions of atopy. Linkage to plant allergens exceeding the LOD > 2.0 was detected at 5q33 (D5S1507, LOD = 2.11, P = 0.0009) and 13q14 (D13S165, LOD = 2.74, P = 0.0002). The significant association with plant allergens (quantitative and discrete traits) was found at 7p14 (D7S2250, corrected P = 0.026) and 12q13 (D12S1298, corrected P = 0.043). Thus, the finding of linkage on chromosome 8q12 shows precision and predictive power of mouse models in the investigation of complex traits in humans. Our results also confirm the role of loci at 5q33, 7p14, 12q14, and 13q13 in control of IgE.

• MeSH
• alergeny škodlivé účinky   imunologie   MeSH
• atopická dermatitida etnologie   genetika   imunologie   MeSH
• časná přecitlivělost etnologie   genetika   MeSH
• dítě MeSH
• dospělí MeSH
• druhová specificita MeSH
• epigeneze genetická genetika   MeSH
• etnicita genetika   MeSH
• genetická predispozice k nemoci MeSH
• imunoglobulin E biosyntéza   krev   imunologie   MeSH
• kvantitativní znak dědičný MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidské chromozomy, pár 8 genetika   MeSH
• Lod skóre MeSH
• mapování chromozomů * MeSH
• mladiství MeSH
• myši genetika   imunologie   MeSH
• potravinová alergie etnologie   genetika   imunologie   MeSH
• respirační alergie etnologie   genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• myši genetika   imunologie   MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• alergeny MeSH
• imunoglobulin E MeSH

Major histocompatibility complex (MHC) genes play important role in host-parasite interactions and parasites are crucial factors influencing the population dynamics of hosts. We described the structure and diversity of exon 2 of the MHC class II DQA gene in three species of voles (Arvicolinae) exhibiting regular multi-annual fluctuations of population density and analysed the processes leading to the observed MHC polymorphism. By using cloning-sequencing methodology and capillary electrophoresis-single strand conformation polymorphism, we described seven sequences in the water, eight in the common, and seven in the bank voles coming from an area of 70 km(2) around the Nozeroy canton in the Jura Mountains (Franche Comté, France). All exon 2 sequences translate to give unique amino acid sequences and positive selection was found to act very intensively on antigen binding sites. We documented the presence of recombination at vole DQA region but its importance in generating allelic polymorphism seems to be relatively limited. For the first time within rodents, we documented the duplication of the DQA gene in all three species with both copies being transcriptionally active. Phylogenetic analysis of allelic sequences revealed extensive trans-species polymorphism within the subfamily although no alleles were shared between species in our data set. We discuss possible role of parasites in forming the recent polymorphism pattern of the DQA locus in voles.

• MeSH
• alely MeSH
• Arvicolinae genetika   imunologie   MeSH
• duplikace genu * MeSH
• elektroforéza kapilární MeSH
• fylogeneze MeSH
• geny MHC třídy II genetika   MeSH
• HLA-DQ antigeny genetika   MeSH
• HLA-DQ beta řetězec MeSH
• klonování DNA MeSH
• molekulární evoluce MeSH
• molekulární sekvence - údaje MeSH
• polymorfismus konformace jednovláknové DNA * MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční analýza DNA MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• HLA-DQ antigeny MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DQbeta antigen MeSH Prohlížeč

Systematic assessment of the role of host genes in clinico-pathological and immunological manifestations of Leishmania major-induced disease in mice was performed using 20 recombinant congenic (RC) strains. As the RC strains are homozygous and each carries a different, random set of 12.5% genes from the resistant strain, STS/A, and 87.5% genes from the susceptible strain, BALB/cHeA, they allowed us to study the pathological and immunological characteristics of infected hosts in 20 fixed different random combinations of BALB/c and STS genes. The 20 RC strains differ widely in expression of different symptoms of disease and in immunological characteristics. Disease or healing in different strains occurred in association with different components of immune response -- with the exception of a frequently occurring correlation between the disease and IgE levels. Moreover, some parameters of the immune response were highly correlated in some strains but not at all in others. This shows that several patterns of the immune response may be associated with the same clinical outcome, depending on the host genotype. Our data also suggest that despite the complexity of regulation, when a sufficient number of controlling loci is known, the prediction of a phenotype is possible. Combining functional and clinical information with multilocus genotyping may improve our ability to predict the progression of the disease and to optimize the treatment.

• MeSH
• cytokiny krev   MeSH
• druhová specificita MeSH
• genetická predispozice k nemoci MeSH
• genetická variace MeSH
• imunoglobulin E krev   MeSH
• kinetika MeSH
• Leishmania major MeSH
• leishmanióza genetika   imunologie   patologie   MeSH
• modely genetické MeSH
• modely nemocí na zvířatech * MeSH
• myši inbrední BALB C MeSH
• myši kongenní genetika   imunologie   MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• imunoglobulin E MeSH