The major histocompatibility complex (MHC) with its class I and II genes plays a crucial role in the immune response to pathogens by presenting oligopeptide antigens to various immune response effector cells. In order to counteract the vast variability of infectious agents, MHC class I and II genes usually retain high levels of SNPs mainly concentrated in the exons encoding the antigen binding sites. The aim of the study was to reveal new variability of selected MHC genes with a special focus on MHC class I physical haplotypes. Long-range NGS to was used to identify exon 2-exon 3 alleles in three genetically distinct horse breeds. A total of 116 allelic variants were found in the MHC class I genes Eqca-1, Eqca-2, Eqca-7 and Eqca-Ψ, 112 of which were novel. The MHC class II DRA locus was confirmed to comprise five exon 2 alleles, and no new sequences were observed. Additional variability in terms of 15 novel exon 2 alleles was identified in the DQA1 locus. Extensive overall variability across the entire MHC region was confirmed by an analysis of MHC-linked microsatellite loci. Both diversifying and purifying selection were detected within the MHC class I and II loci analyzed.

• Klíčová slova
• Eqca, Equus caballus, MHC, MHC class I, MHC class II, MSATs,
• MeSH
• alely MeSH
• exony genetika   MeSH
• geny MHC třídy II * MeSH
• hlavní histokompatibilní komplex MeSH
• koně genetika   MeSH
• MHC antigeny I. třídy * MeSH
• MHC antigeny II. třídy genetika   MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• MHC antigeny I. třídy * MeSH
• MHC antigeny II. třídy 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

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.

• MeSH
• celogenomová asociační studie metody   MeSH
• genetická heterogenita MeSH
• heterozygot MeSH
• lidé MeSH
• MHC antigeny I. třídy genetika   MeSH
• MHC antigeny II. třídy genetika   MeSH
• nehodgkinský lymfom genetika   MeSH
• prospektivní studie MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• MHC antigeny I. třídy MeSH
• MHC antigeny II. třídy MeSH

Among bird species, the most studied major histocompatibility complex (MHC) is the chicken MHC. Although the number of studies on MHC in free-ranging species is increasing, the knowledge on MHC variation in species closely related to chicken is required to understand the peculiarities of bird MHC evolution. Here we describe the variation of MHC class IIB (MHCIIB) exon 2 in a population of the Grey partridge (Perdix perdix), a species of high conservation concern throughout Europe and an emerging galliform model in studies of sexual selection. We found 12 alleles in 108 individuals, but in comparison to other birds surprisingly many sites show signatures of historical positive selection. Individuals displayed between two to four alleles both on genomic and complementary DNA, suggesting the presence of two functional MHCIIB loci. Recombination and gene conversion appear to be involved in generating MHCIIB diversity in the Grey partridge; two recombination breakpoints and several gene conversion events were detected. In phylogenetic analysis of galliform MHCIIB, the Grey partridge alleles do not cluster together, but are scattered through the tree instead. Thus, our results indicate that the Grey partridge MHCIIB is comparable to most other galliforms in terms of copy number and population polymorphism.

• MeSH
• alely MeSH
• druhová specificita MeSH
• exony genetika   MeSH
• fylogeneze MeSH
• Galliformes genetika   MeSH
• genová konverze * MeSH
• MHC antigeny II. třídy chemie   genetika   MeSH
• molekulární sekvence - údaje MeSH
• polymorfismus genetický * MeSH
• pravděpodobnostní funkce MeSH
• regulace genové exprese MeSH
• rekombinace genetická genetika   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• sekvenční seřazení MeSH
• selekce (genetika) * MeSH
• substituce aminokyselin genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• MHC antigeny II. třídy MeSH

BACKGROUND: The Major Histocompatibility Complex (MHC) is a genomic region containing genes with crucial roles in immune responses. MHC class I and class II genes encode antigen-presenting molecules expressed on the cell surface. To counteract the high variability of pathogens, the MHC evolved into a region of considerable heterogeneity in its organization, number and extent of polymorphism. Studies of MHCs in different model species contribute to our understanding of mechanisms of immunity, diseases and their evolution. Camels are economically important domestic animals and interesting biomodels. Three species of Old World camels have been recognized: the dromedary (Camelus dromedarius), Bactrian camel (Camelus bactrianus) and the wild camel (Camelus ferus). Despite their importance, little is known about the MHC genomic region, its organization and diversity in camels. The objectives of this study were to identify, map and characterize the MHC region of Old World camelids, with special attention to genetic variation at selected class MHC II loci. RESULTS: Physical mapping located the MHC region to the chromosome 20 in Camelus dromedarius. Cytogenetic and comparative analyses of whole genome sequences showed that the order of the three major sub-regions is "Centromere - Class II - Class III - Class I". DRA, DRB, DQA and DQB exon 2 sequences encoding the antigen binding site of the corresponding class II antigen presenting molecules showed high degree of sequence similarity and extensive allele sharing across the three species. Unexpectedly low extent of polymorphism with low numbers of alleles and haplotypes was observed in all species, despite different geographic origins of the camels analyzed. The DRA locus was found to be polymorphic, with three alleles shared by all three species. DRA and DQA sequences retrieved from ancient DNA samples of Camelus dromedarius suggested that additional polymorphism might exist. CONCLUSIONS: This study provided evidence that camels possess an MHC comparable to other mammalian species in terms of its genomic localization, organization and sequence similarity. We described ancient variation at the DRA locus, monomorphic in most species. The extent of molecular diversity of MHC class II genes seems to be substantially lower in Old World camels than in other mammalian species.

• MeSH
• alely MeSH
• exony MeSH
• fylogeneze MeSH
• fyzikální mapování chromozomů MeSH
• geny MHC třídy II * MeSH
• haplotypy MeSH
• molekulární sekvence - údaje MeSH
• polymorfismus genetický * MeSH
• sekvence nukleotidů MeSH
• velbloudi genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The D region of the HLA system is very complex. Three loci, HLA-DR, DQ and DP, are now very well established. However, the question of the independence of the first known locus of this region remains elusive--it is not yet known if HLA-D antigens are really independent or if they represent some epitopes on the molecules of HLA-DR/DQ antigens. The HLA-DP antigens represent an independent series in the HLA system recognized by the PLT technique. On the other hand, the HLA-PL antigens also detected by PLT correlate with both HLA-D and HLA-DR antigens, and it seems that they do not constitute an independent group of HLA antigens.

• MeSH
• geny MHC třídy II MeSH
• H-2 antigeny analýza   MeSH
• HLA antigeny analýza   MeSH
• HLA-D antigeny analýza   MeSH
• hlavní histokompatibilní komplex * MeSH
• homozygot MeSH
• lidé MeSH
• lymfocyty imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• H-2 antigeny MeSH
• HLA antigeny MeSH
• HLA-D antigeny MeSH

The genomic structure of the Major Histocompatibility Complex (MHC) region and variation in selected MHC class I related genes in Old World camels, Camelus bactrianus and Camelus dromedaries were studied. The overall genomic organization of the camel MHC region follows a general pattern observed in other mammalian species and individual MHC loci appear to be well conserved. Selected MHC class I genes B-67 and BL3-7 exhibited unexpectedly low variability, even when compared to other camel MHC class I related genes MR1 and MICA. Interspecific SNP and allele sharing are relatively common, and frequencies of heterozygotes are usually low. Such a low variation in a genomic region generally considered as one of the most polymorphic in vertebrate genomes is unusual. Evolutionary relationships between MHC class I related genes and their counterparts from other species seem to be rather complex. Often, they do not follow the general evolutionary history of the species concerned. Close evolutionary relationships of individual MHC class I loci between camels, humans and dogs were observed. Based on the results of this study and on our data on MHC class II genes, the extent and the pattern of polymorphism of the MHC region of Old World camelids differed from most mammalian groups studied so far. Camels thus seem to be an important model for our understanding of the role of genetic diversity in immune functions, especially in the context of unique features of their immunoglobulin and T-cell receptor genes.

• Klíčová slova
• MHC class I, MICA, MR1, SNP, camel, polymorphism,
• MeSH
• druhová specificita MeSH
• fylogeneze * MeSH
• jednonukleotidový polymorfismus * MeSH
• MHC antigeny I. třídy * genetika   imunologie   MeSH
• molekulární evoluce * MeSH
• velbloudi * genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• MHC antigeny I. třídy * MeSH

The major histocompatibility complex (MHC) genes coding for antigen presenting molecules are the most polymorphic genes in vertebrate genome. The MHC class II DRA gene shows only small variation in many mammalian species, but it exhibits relatively high level of polymorphism in Equidae, especially in donkeys. This extraordinary degree of polymorphism together with signatures of selection in specific amino acids sites makes the donkey DRA gene a suitable model for population diversity studies. The objective of this study was to investigate the DRA gene diversity in three different populations of donkeys under infectious pressure of protozoan parasites, Theileria equi and Babesia caballi. Three populations of domestic donkeys from Italy (N = 68), Jordan (N = 43), and Kenya (N = 78) were studied. A method of the donkey MHC DRA genotyping based on PCR-RFLP and sequencing was designed. In addition to the DRA gene, 12 polymorphic microsatellite loci were genotyped. The presence of Theileria equi and Babesia caballi parasites in peripheral blood was investigated by PCR. Allele and genotype frequencies, observed and expected heterozygosities and F(IS) values were computed as parameters of genetic diversity for all loci genotyped. Genetic distances between the three populations were estimated based on F(ST) values. Statistical associations between parasite infection and genetic polymorphisms were sought. Extensive DRA locus variation characteristic for Equids was found. The results showed differences between populations both in terms of numbers of alleles and their frequencies as well as variation in expected heterozygosity values. Based on comparisons with neutral microsatellite loci, population sub-structure characteristics and association analysis, convincing evidence of pathogen-driven selection at the population level was not provided. It seems that genetic diversity observed in the three populations reflects mostly effects of selective breeding and their different genetic origins.

• MeSH
• babezióza epidemiologie   veterinární   MeSH
• demografie MeSH
• Equidae genetika   metabolismus   MeSH
• genetická variace * MeSH
• genotyp MeSH
• geny MHC třídy II genetika   MeSH
• mikrosatelitní repetice MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Afrika epidemiologie   MeSH
• Asie epidemiologie   MeSH
• Evropa epidemiologie   MeSH

More than two nucleotide sequences of the second exon of the ELA-DQB region retrieved from a single animal and two different sequences isolated from horses homozygous in the major histocompatibility complex (MHC) region by descent indicated the existence of at least two ELA-DQB loci at the genomic level. New alleles detected by polymerase chain reaction single strand conformation polymorphism (SSCP) and defined by nucleotide sequencing of the second exon of the DQB gene(s) were described. Based on the level of nucleotide sharing, at least two groups of alleles were shown to exist. The newly defined alleles belonged preferentially to one of the groups. However, their specific locus assignment was not possible from the data collected. At least one of these alleles was shown to be transcribed. No frame-shift mutations were identified among the new alleles, although one pseudoallele containing a stop codon was identified at the genomic DNA level.

• MeSH
• alely * MeSH
• Equidae genetika   MeSH
• genom MeSH
• MHC antigeny II. třídy genetika   MeSH
• molekulární sekvence - údaje MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus konformace jednovláknové DNA 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
• MHC antigeny II. třídy MeSH

Histocompatibility antigens play a fundamental role in the immune functions by their polymorphic capture structure for binding exogenous and endogenous peptides and presenting them to the appropriate T and B cell receptors. The genetic background of the control of synthesis of the histocompatibility antigens is very complex including several loci controlling the wide polymorphic variation of class I and class II histocompatibility molecules and their regulation of expression. Most significant variability in the presence or absence of histocompatibility antigens could be observed during development, differentiation, and activation. The tissue-specific expression is influenced by pathological events such as malignant transformation, viral infection and genetic defectiveness as well. The research in the field of molecular genetics of the MHC in the last decade revealed, upstream of the coding genes of class I and class II molecules, a very complex regulatory machinery including a series of genes termed enhancer and promoter region. At the DNA level, various gene boxes and regulatory elements were discovered, which are activated by the binding of the appropriate histone proteins, cytokines or hormones responsible for the upregulation and downregulation of histocompatibility antigen expression. Regulation is mainly functioning at the transcriptional level, but other factors such as viral proteins, oncogenes, biomolecules, and physical effects take part, either indirectly or directly affecting the regulatory genes and DNA binding proteins. The increasing knowledge about the regulatory machinery may lead to the introduction of genetic manipulation, either experimental or clinical, with the aim of changing the expression of histocompatibility molecules on the cell surface in order to achieve normal or demanded immune functions.

• MeSH
• B-lymfocyty imunologie   MeSH
• buněčná membrána imunologie   MeSH
• genetické nemoci vrozené imunologie   MeSH
• geny MHC třídy I * MeSH
• geny MHC třídy II * MeSH
• HLA-D antigeny biosyntéza   genetika   MeSH
• hlavní histokompatibilní komplex * MeSH
• lidé MeSH
• MHC antigeny I. třídy biosyntéza   genetika   MeSH
• MHC antigeny II. třídy biosyntéza   genetika   MeSH
• nádorová transformace buněk imunologie   MeSH
• receptory antigenů B-buněk imunologie   MeSH
• receptory antigenů T-buněk imunologie   MeSH
• regulace genové exprese * MeSH
• T-lymfocyty imunologie   MeSH
• upregulace MeSH
• virové nemoci imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• HLA-D antigeny MeSH
• MHC antigeny I. třídy MeSH
• MHC antigeny II. třídy MeSH
• receptory antigenů B-buněk MeSH
• receptory antigenů T-buněk MeSH