Polymorphic Major Histocompatibility Complex Research Articles

Cape Feather Coloration Signals Different Genotypes of the Most Polymorphic MHC Locus in Male Golden Pheasants (Chrysolophus pictus).

Simple SummaryOrnamental feather coloration in birds is deemed an honest signal of male quality, but is seldom embodied at the functional genetic level. The major histocompatibility complex is involved in the immune response, thereby affecting an organism’s fitness. Here, we tested the hypothesis that the coloration of the cape feather signals genetic quality in the male golden pheasant. We measured brightness, chroma, and hue as the main parameters to quantify color differences. Then, we investigated the genotypes of all major histocompatibility complex loci associated with adaptive immunity. The results showed that heterozygosity of the most polymorphic major histocompatibility complex locus was positively related with the brightness and chroma of cape feathers. Our study suggested that cape feather coloration might signal different genotypes of the most polymorphic major histocompatibility complex locus in male golden pheasants.Ornamental feather coloration is usually a reflection of male quality and plays an important role during courtship, whereas the essence of male quality at the genetic level is not well understood. Major histocompatibility complex (MHC)-based mate choice has been observed in various vertebrates. Here, we investigated the relationship between the coloration of cape feathers and the MHC genotypes in golden pheasants (Chrysolophus pictus). We found that feather coloration differed sharply among different individuals (brightness: 1827.20 ± 759.43, chroma: 1241.90 ± 468.21, hue: 0.46 ± 0.06). Heterozygous individuals at the most polymorphic MHC locus (IA2) had brighter feathers than homozygous individuals (Z = −2.853, p = 0.004) and were more saturated in color (Z = −2.853, p = 0.004). However, feather coloration was not related to other MHC loci or to overall genetic heterozygosity (p > 0.050). Our study suggested that coloration of cape feathers might signal IA2 genotypes in golden pheasants.

The Bovine Major Histocompatibility Complex and Its Role in Tick and Tick-borne Disease Resistance and Immune Responsiveness in Bos Indicus and their Crosses with Bos Taurus in Sub-Saharan Africa: A Review

Ticks present a major challenge in livestock production given the increased demand for animal protein worldwide. Ticks cause worry, blood loss, damage hides and most importantly they are vectors of pathogens that cause severe diseases in livestock. Economic losses caused by ticks amounts to billions of dollars annually. The primary tick control method relies heavily on the use of acaricides. The increasing prices of these chemicals, environmental pollution, chemical residues in animal products and most importantly evolution of resistance of ticks to almost all available acaricides, has frustrated efforts of farmers to control ticks and tick-borne diseases. This has motivated researchers to search for alternative methods of tick control. The Major Histocompatibility complex (MHC) which is called Bovine Leuckocyte Antigen (BoLA) in cattle is an important component of the immune system which plays a major role in immune responses. The BoLA-DRB3 gene is the most polymorphic MHC class II gene locus where numerous associations have been found between the MHC polymorphism and disease resistance making it a good gene candidate for tick resistance. The Bos indicus breed is known to be more resistant to ticks and tick-borne diseases than the Bos Taurus. The use of tick and tick-borne disease resistant cattle breeds is a promising choice for tick and tick-borne disease control given the downsides of acaricides, vaccines and other tick control methods. This review summarizes available information on ticks and tick-borne diseases and the role of the Major Histocompatibility Complex in tick and tick-borne disease resistance.

Marriage does not relate to major histocompatibility complex: a genetic analysis based on 3691 couples.

Optimization of chances for healthy offspring is thought to be one of the factors driving mate choice and compatibility of the major histocompatibility complex (MHC) is assumed to determine the offspring's fitness. While humans have been claimed to be able to perceive information of MHC compatibility via the olfactory channel, it remains unknown whether humans use such information for mate choice. By investigation of 3691 married couples, we observed that the high polymorphism of MHC leads to a low chance for homozygous offspring. MHC similarity between couples did not differ from chance, we hence observed no MHC effect in married couples. Hormonal contraception at the time of relationship initiation had no significant effect towards enhanced similarity. A low variety of alleles within a postcode area led to a higher likelihood of homozygous offspring. Based on this data, we conclude that there is no pattern of MHC dis-assortative mating in a genetically diverse Western society. We discuss the question of olfactory mate preference, in-group mating bias and the high polymorphism as potential explanations.

Estimating the Binding of Sars-CoV-2 Peptides to HLA Class I in Human Subpopulations Using Artificial Neural Networks.

Epidemiological studies show that SARS-CoV-2 infection leads to severe symptoms only in a fraction of patients, but the determinants of individual susceptibility to the virus are still unknown. The major histocompatibility complex (MHC) class I exposes viral peptides in all nucleated cells and is involved in the susceptibility to many human diseases. Here, we use artificial neural networks to analyze the binding of SARS-CoV-2 peptides with polymorphic human MHC class I molecules. In this way, we identify two sets of haplotypes present in specific human populations: the first displays weak binding with SARS-CoV-2 peptides, while the second shows strong binding and T cell propensity. Our work offers a useful support to identify the individual susceptibility to COVID-19 and illustrates a mechanism underlying variations in the immune response to SARS-CoV-2. A record of this paper’s transparent peer review process is included in the Supplemental Information.

Characterization of two MHC II genes (DOB, DRB) in white-tailed deer (Odocoileus virginianus)

BackgroundThe major histocompatibility complex (MHC) is responsible for detecting and addressing foreign pathogens inside the body. While the general structure of MHC genes is relatively well conserved among mammalian species, it is notably different among ruminants due to a chromosomal inversion that splits MHC type II genes into two subregions (IIa, IIb). Recombination rates are reportedly high between these subregions, and a lack of linkage has been documented in domestic ruminants. However, no study has yet examined the degree of linkage between these subregions in a wild ruminant. The white-tailed deer (Odocoileus virginianus), a popular ruminant of the Cervidae family, is habitually plagued by pathogens in its natural environment (e.g. Haemonchus contortus, Elaeophora). Due to the association between MHC haplotypes and disease susceptibility, a deeper understanding of MHC polymorphism and linkage between MHC genes can further aid in this species’ successful management. We sequenced MHC-DRB exon 2 (IIa) and MHC-DOB exon 2 (IIb) on the MiSeq platform from an enclosed white-tailed deer population located in Alabama.ResultsWe identified 12 new MHC-DRB alleles, and resampled 7 alleles, which along with other published alleles brings the total number of documented alleles in white-tailed deer to 30 for MHC-DRB exon 2. The first examination of MHC-DOB in white-tailed deer found significantly less polymorphism (11 alleles), as was expected of a non-classical MHC gene. While MHC-DRB was found to be under positive, diversifying selection, MHC-DOB was found to be under purifying selection for white-tailed deer. We found no significant linkage disequilibrium between MHC-DRB and MHC-DOB, suggesting that these loci are unlikely to be closely linked.ConclusionsOverall, this study identified 12 new MHC-DRB exon 2 alleles and characterized a new, non-classical, MHC II gene (MHC-DOB) for white-tailed deer. We also found a lack of significant linkage between these two loci, which supports previous findings of a chromosomal inversion within the MHC type II gene region in ruminants, and suggests that white-tailed deer may have a recombination hotspot between these MHC regions similar to that found for Bos taurus.

Capturing Differential Allele-Level Expression and Genotypes of All Classical HLA Loci and Haplotypes by a New Capture RNA-Seq Method.

The highly polymorphic human major histocompatibility complex (MHC) also known as the human leukocyte antigen (HLA) encodes class I and II genes that are the cornerstone of the adaptive immune system. Their unique diversity (>25,000 alleles) might affect the outcome of any transplant, infection, and susceptibility to autoimmune diseases. The recent rapid development of new next-generation sequencing (NGS) methods provides the opportunity to study the influence/correlation of this high level of HLA diversity on allele expression levels in health and disease. Here, we describe the NGS capture RNA-Seq method that we developed for genotyping all 12 classical HLA loci (HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DRB4, and HLA-DRB5) and assessing their allelic imbalance by quantifying their allele RNA levels. This is a target enrichment method where total RNA is converted to a sequencing-ready complementary DNA (cDNA) library and hybridized to a complex pool of RNA-specific HLA biotinylated oligonucleotide capture probes, prior to NGS. This method was applied to 161 peripheral blood mononuclear cells and 48 umbilical cord blood cells of healthy donors. The differential allelic expression of 10 HLA loci (except for HLA-DRA and HLA-DPA1) showed strong significant differences (P < 2.1 × 10−15). The results were corroborated by independent methods. This newly developed NGS method could be applied to a wide range of biological and medical questions including graft rejections and HLA-related diseases.

Sequence-structure-function relationships in class I MHC: A local frustration perspective.

Class I Major Histocompatibility Complex (MHC) binds short antigenic peptides with the help of Peptide Loading Complex (PLC), and presents them to T-cell Receptors (TCRs) of cytotoxic T-cells and Killer-cell Immunglobulin-like Receptors (KIRs) of Natural Killer (NK) cells. With more than 10000 alleles, human MHC (Human Leukocyte Antigen, HLA) is the most polymorphic protein in humans. This allelic diversity provides a wide coverage of peptide sequence space, yet does not affect the three-dimensional structure of the complex. Moreover, TCRs mostly interact with HLA in a common diagonal binding mode, and KIR-HLA interaction is allele-dependent. With the aim of establishing a framework for understanding the relationships between polymorphism (sequence), structure (conserved fold) and function (protein interactions) of the human MHC, we performed here a local frustration analysis on pMHC homology models covering 1436 HLA I alleles. An analysis of local frustration profiles indicated that (1) variations in MHC fold are unlikely due to minimally-frustrated and relatively conserved residues within the HLA peptide-binding groove, (2) high frustration patches on HLA helices are either involved in or near interaction sites of MHC with the TCR, KIR, or tapasin of the PLC, and (3) peptide ligands mainly stabilize the F-pocket of HLA binding groove.

MHC-DRB1 exon 2 polymorphism and its association with mycoplasma ovipneumonia resistance or susceptibility genotypes in sheep

Major histocompatibility complex (MHC) polymorphisms are associated with animal and human diseases. However, only a few studies have reported an association between MHC polymorphisms and mycoplasma ovipneumonia (MO). In the present study, three resistance/susceptibility genotypes associated with MO were identified by polymerase chain reaction-restriction fragment length polymorphism genotyping, assessing the clinical and pathological features, and examining the immune factors. The current results showed that MvaI bb and HaeIII ee were dominant genotypes in the susceptible Hu population, while MO-resistant populations, Dorper and D 9 H hybrids, were dominated by the MvaI cc and HaeIII dd genotypes, suggesting that MvaI cc and HaeIII dd genotypes might be associated with the trait of MO resistance. Further, the clinical symptoms and pathological morphology in the susceptibility group infected with MO were more severe than those in the resistant groups infected similarly. The data on the changes in the immune factor responses were utilized to deduce the molecular mechanism underlying the MO resistance/susceptibility. The results showed that the susceptible genotypes promote the inflammatory responses by inducing a high expression of TNFa, IFNc, IL-4, IL-6, and IL-1b, while the resistant genotypes inhibit the inflammatory response by increasing the expression of IL-2 and IL-10 significantly. This finding would provide the theoretical guidance for propagating sheep breeds that are highly resistant to MO.

Determinants governing T cell receptor α/β-chain pairing in repertoire formation of identical twins

The T cell repertoire in each individual includes T cell receptors (TCRs) of enormous sequence diversity through the pairing of diverse TCR α- and β-chains, each generated by somatic recombination of paralogous gene segments. Whether the TCR repertoire contributes to susceptibility to infectious or autoimmune diseases in concert with disease-associated major histocompatibility complex (MHC) polymorphisms is unknown. Due to a lack in high-throughput technologies to sequence TCR α-β pairs, current studies on whether the TCR repertoire is shaped by host genetics have so far relied only on single-chain analysis. Using a high-throughput single T cell sequencing technology, we obtained the largest paired TCRαβ dataset so far, comprising 965,523 clonotypes from 15 healthy individuals including 6 monozygotic twin pairs. Public TCR α- and, to a lesser extent, TCR β-chain sequences were common in all individuals. In contrast, sharing of entirely identical TCRαβ amino acid sequences was very infrequent in unrelated individuals, but highly increased in twins, in particular in CD4 memory T cells. Based on nucleotide sequence identity, a subset of these shared clonotypes appeared to be the progeny of T cells that had been generated during fetal development and had persisted for more than 50 y. Additional shared TCRαβ in twins were encoded by different nucleotide sequences, implying that genetic determinants impose structural constraints on thymic selection that favor the selection of TCR α-β pairs with entire sequence identities.

Molecular polymorphism and expression of MHC I α, II α, II β and II invariant chain in the critically endangered Dabry's sturgeon (Acipenser dabryanus)

The major histocompatibility complex (MHC) is a key player in the regulation of immune responses through presenting foreign antigens to T lymphocytes. In this study, three MHC genes, namely, MHC I α, II α, II β and the II invariant chain (Ii), were identified and characterized in the critically endangered Dabry's sturgeon (Acipenser dabryanus). A tissue distribution study showed that the MHC and Ii transcripts were widely expressed in various tissues. The highest expression levels of MHC I α, II α and Ii were found in the gill, while MHC II β was primarily expressed in the spleen. Challenge of A. dabryanus with a pathogenic bacterium in vivo resulted in significant upregulation of both MHC and Ii expression, indicating potential roles of these genes in immune response. Phylogenetic analysis showed that A. dabryanus MHC grouped with other teleost MHC genes and sequences from Polyodon spathula and A. dabryanus had an intermingling of alleles. According to the split time between paddlefishes and sturgeons, this result indicated that trans-species MHC lineages in Chondrostei were much older than those in tetrapods. The molecular polymorphisms of the complete open reading frame regions of the MHC genes were analysed in several A. dabryanus individuals. MHC II α and II β were highly polymorphic in different individuals, while MHC I α was more conserved. The ratio of non-synonymous substitution occurred at a significantly higher frequency than synonymous substitution in peptide-binding regions (PBR) of MHC II α and II β, demonstrating the existence of positive selection at peptide-binding sites. Our study suggested potential roles of the MHC chains in immune response to pathogen microbial infection, and the numerous alleles identified in this study will help further genetic management and molecular marker-assisted selective breeding programmes in A. dabryanus.

Germline-Encoded TCR-MHC Contacts Promote TCR V Gene Bias in Umbilical Cord Blood T Cell Repertoire.

T cells recognize antigens as peptides bound to major histocompatibility complex (MHC) proteins through T cell receptors (TCRs) on their surface. To recognize a wide range of pathogens, each individual possesses a substantial number of TCRs with an extremely high degree of variability. It remains controversial whether germline-encoded TCR repertoire is shaped by MHC polymorphism and, if so, what is the preference between MHC genetic variants and TCR V gene compatibility. To investigate the “net” genetic association between MHC variations and TRBV genes, we applied quantitative trait locus (QTL) mapping to test the associations between MHC polymorphism and TCR β chain V (TRBV) genes usage using umbilical cord blood (UCB) samples of 201 Chinese newborns. We found TRBV gene and MHC loci that are predisposed to interact with one another differ from previous conclusions. The majority of MHC amino acid residues associated with the TRBV gene usage show spatial proximities in known structures of TCR-pMHC complexes. These results show for the first time that MHC variants bias TRBV gene usage in UCB of Chinese ancestry and indicate that germline-encoded contacts influence TCR-MHC interactions in intact T cell repertoires.

MHC structuring and divergent allele advantage in a urodele amphibian: a hierarchical multi-scale approach.

Proteins encoded by extraordinarily polymorphic major histocompatibility complex (MHC) genes are involved in the adaptive immune response. Balancing selection is believed to maintain MHC polymorphism in the long term, although neutral processes also play a role in shaping MHC diversity. However, the relative contribution of these processes is poorly understood. Here we characterized MHC class II variation of a low-dispersal, pond-breeding newt (Triturus carnifex) over a restricted, geographically structured area. We aimed to (1) evaluate the contribution of selection and neutral processes to shaping MHC diversity at two geographic scales, and (2) test for signatures of divergent allele advantage (DAA), which is a potentially important mechanism of balancing selection. The dominant role of selection in shaping MHC variation was suggested by the lack of correlation between MHC and neutral (microsatellite) variation. Although most variation occurred within populations for both types of markers, they differed in the extent of structuring at the two spatial scales. MHC structuring was more pronounced at local scales, suggesting the role of local selection, while structuring was not detectable at a larger scale, possibly due to the effect of balancing selection. Microsatellites showed the opposite pattern. As expected under DAA, the observed genotypes combined more sequence diversity than expected under a random association of alleles. Thus, DAA may contribute to maintaining MHC polymorphism, which is ancient, as supported by signatures of historical positive selection and trans-species polymorphism. Our results point to the importance of a multi-scale approach in studying MHC variation, especially in low-dispersal taxa, which are genetically structured at fine spatial scales.

Major Histocompatibility Complex (MHC) Genes and Disease Resistance in Fish.

Fascinating about classical major histocompatibility complex (MHC) molecules is their polymorphism. The present study is a review and discussion of the fish MHC situation. The basic pattern of MHC variation in fish is similar to mammals, with MHC class I versus class II, and polymorphic classical versus nonpolymorphic nonclassical. However, in many or all teleost fishes, important differences with mammalian or human MHC were observed: (1) The allelic/haplotype diversification levels of classical MHC class I tend to be much higher than in mammals and involve structural positions within but also outside the peptide binding groove; (2) Teleost fish classical MHC class I and class II loci are not linked. The present article summarizes previous studies that performed quantitative trait loci (QTL) analysis for mapping differences in teleost fish disease resistance, and discusses them from MHC point of view. Overall, those QTL studies suggest the possible importance of genomic regions including classical MHC class II and nonclassical MHC class I genes, whereas similar observations were not made for the genomic regions with the highly diversified classical MHC class I alleles. It must be concluded that despite decades of knowing MHC polymorphism in jawed vertebrate species including fish, firm conclusions (as opposed to appealing hypotheses) on the reasons for MHC polymorphism cannot be made, and that the types of polymorphism observed in fish may not be explained by disease-resistance models alone.

HLA-E: exploiting pathogen-host interactions for vaccine development.

SummaryViruses, when used as vectors for vaccine antigen delivery, can induce strong cellular and humoral responses against target epitopes. Recent work by Hansen et al. describes the use of a cytomegalovirus‐vectored vaccine, which is able to generate a stable effector‐memory T cell population at the sites of vaccination in rhesus macaques. This vaccine, targeted towards multiple epitopes in simian immunodeficiency virus (SIV), did not induce classical CD8+ T cells. However, non‐canonical CD8+ T cell induction occurred via major histocompatibility complex (MHC) class II and MHC‐E. The MHC‐E‐restricted T cells could recognize broad epitopes across the SIV peptides, and conferred protection against viral challenge to 55% of vaccinated macaques. The human homologue, human leucocyte antigen (HLA)‐E, is now being targeted as a new avenue for vaccine development. In humans, HLA‐E is an unusually oligomorphic class Ib MHC molecule, in comparison to highly polymorphic MHC class Ia. Whereas MHC class Ia presents peptides derived from pathogens to T cells, HLA‐E classically binds defined leader peptides from class Ia MHC peptides and down‐regulates NK cell cytolytic activity when presented on the cell surface. HLA‐E can also restrict non‐canonical CD8+ T cells during natural infection with various pathogens, although the extent to which they are involved in pathogen control is mostly unknown. In this review, an overview is provided of HLA‐E and its ability to interact with NK cells and non‐canonical T cells. Also discussed are the unforeseen beneficial effects of vaccination, including trained immunity of NK cells from bacille Calmette–Guérin (BCG) vaccination, and the broad restriction of non‐canonical CD8+ T cells by cytomegalovirus (CMV)‐vectored vaccines in pre‐clinical trials.

Divergent Allele Advantage Provides a Quantitative Model for Maintaining Alleles with a Wide Range of Intrinsic Merits.

The Major Histocompatibility Complex (MHC) is the most genetically diverse region of the genome in most vertebrates. Some form of balancing selection is necessary to account for the extreme diversity, but the precise mechanism of balancing selection is unknown. Due to the way MHC molecules determine immune recognition, overdominance (also referred to as heterozygote advantage) has been suggested as the main driving force behind this unrivalled diversity. However, both theoretical results and simulation models have shown that overdominance in its classical form cannot maintain large numbers of alleles unless all alleles confer unrealistically similar levels of fitness. There is increasing evidence that heterozygotes containing genetically divergent alleles allow for broader antigen presentation to immune cells, providing a selective mechanism for MHC polymorphism. By framing competing models of overdominance within a general framework, we show that a model based on Divergent Allele Advantage (DAA) provides a superior mechanism for maintaining alleles with a wide range of intrinsic merits, as intrinsically less-fit MHC alleles that are more divergent can survive under DAA. Specifically, our results demonstrate that a quantitative mechanism built from the DAA hypothesis is able to maintain polymorphism in the MHC. Applying such a model to both livestock breeding and conservation could provide a better way of identifying superior heterozygotes, and quantifying the advantages of genetic diversity at the MHC.

Two to Tango: Co-evolution of Hominid Natural Killer Cell Receptors and MHC.

Natural killer (NK) cells have diverse roles in hominid immunity and reproduction. Modulating these functions are the interactions between major histocompatibility complex (MHC) class I molecules that are ligands for two NK cell surface receptor types. Diverse killer cell immunoglobulin-like receptors (KIR) bind specific motifs encoded within the polymorphic MHC class I cell surface glycoproteins, while, in more conserved interactions, CD94:NKG2A receptors recognize MHC-E with bound peptides derived from MHC class I leader sequences. The hominid lineage presents a choreographed co-evolution of KIR with their MHC class I ligands. MHC-A, -B, and -C are present in all great apes with species-specific haplotypic variation in gene content. The Bw4 epitope recognized by lineage II KIR is restricted to MHC-B but also present on some gorilla and human MHC-A. Common to great apes, but rare in humans, are MHC-B possessing a C1 epitope recognized by lineage III KIR. MHC-C arose from duplication of MHC-B and is fixed in all great apes except orangutan, where it exists on approximately 50% of haplotypes and all allotypes are C1-bearing. Recent study showed that gorillas possess yet another intermediate MHC organization compared to humans. Like orangutans, but unlike the Pan-Homo species, duplication of MHC-B occurred. However, MHC-C is fixed, and the MHC-C C2 epitope (absent in orangutans) emerges. The evolution of MHC-C drove expansion of its cognate lineage III KIR. Recently, position −21 of the MHC-B leader sequence has been shown to be critical in determining NK cell educational outcome. In humans, methionine (−21M) results in CD94:NKG2A-focused education whereas threonine (−21T) produces KIR-focused education. This is another dynamic position among hominids. Orangutans have exclusively −21M, consistent with their intermediate stage in lineage III KIR-focused evolution. Gorillas have both −21M and −21T, like humans, but they are unequally encoded by their duplicated B genes. Chimpanzees have near-fixed −21T, indicative of KIR-focused NK education. Harmonious with this observation, chimpanzee KIR exhibit strong binding and, compared to humans, smaller differences between binding levels of activating and inhibitory KIR. Consistent between these MHC-NK cell receptor systems over the course of hominid evolution is the evolution of polymorphism favoring the more novel and dynamic KIR system.

Principi di immunobiologia del trapianto ed attivazione della risposta immune

To achieve an effective immune response it is important that T cells can recognize a wide variety of non-self antigens; this allows for restrained immune activation and subsequent antigen-specific killing. This task is accomplished through the generation of a repertoire of T cells in a single individual with specificity for an enormous number of potential foreign antigens presented as peptides on the surface of major histocompatibility complex (MHC) molecules. Variations in MHC structure among individuals increase the variety of peptides that can be presented to T cells; this mechanism protects the species as a whole by ensuring adequate T-cell responses to a given foreign organism. Although slightly different, these MHC polymorphisms expressed in the donor kidney are recognized after kidney transplantation between non genetically-identical humans, and induce alloresponses that in the absence of immunosuppression result in rejection of the allograft. In this chapter, we review basic immunological principles important to the field of kidney transplantation.

The new bovine reference genome assembly provides new insight into genomic organization of the bovine major histocompatibility complex

The reference genome sequence represents a key resource for genetic studies of the target species. In 2009, two reference assemblies of the cattle (Bos taurus) genome, were published (Btau 4.0 and UMD 2.0). Both assemblies were upgraded several times since then. Highly polymorphic major histocompatibility complex (MHC) encodes proteins crucial for immune recognition and regulation of immune response in vertebrates. It is characterised by extensive nucleotide diversity, copy number variation of paralogous genes, and long repetitive sequences. In cattle, MHC is designated as BoLA (bovine leucocyte antigen), located on the chromosome 23. Its organisation differs from typical mammalian MHCs. The structural complexity makes it difficult to assemble a reliable reference sequence of this genomic region. Therefore, this region represents a good genomic model region to compare the accuracy of different assembly strategies. Recent advances in long-read sequence technology, combined with new scaffolding technologies, enabled issuing of the new bovine reference genome assembly build ARS-UCD 1.2, which is significantly improved over previous bovine genome assembly releases. In the current study the software tool Mauve for multiple alignment of conserved genomic sequences with rearrangements was used to identify the differences of genomic organization in the BoLA region assembled in three bovine reference genomes, Btau 5.0.1, UMD 3.1.1, and ARS-UCD 1.2. Multiple alignment of the bovine chromosome 23 sequences extracted from three genome assemblies revealed differences in the structure of the BoLA region. Segments encoding genes BOLA-DMA and BOLA-DQB are rearranged and inverted in the new assembly relative to the previous builds.

An official nomenclature for the major histocompatibility complex allele sequences from the domestic goat (Capra hircus).

Official allelic nomenclature and corresponding databases of validated major histocompatibility complex (MHC) alleles from most of the major species of farmed livestock are now represented on the IPD-MHC Database. The major exception is the domestic goat (Capra hircus) which can lead to confusion in the research community. Here, we propose to start the process of developing such a resource which will support the research community's interests in livestock population genetics, infectious disease research, vaccine development and comparative studies. In this manuscript, we assign the official nomenclature for the major transcribed and highly polymorphic MHC class II DRB1 locus. Additional class II loci including DRA and DQ and MHC class I loci will be added in the future.

Association of bovine major histocompatibility complex (BoLA) gene polymorphism with colostrum and milk microbiota of dairy cows during the first week of lactation

BackgroundThe interplay between host genotype and commensal microbiota at different body sites can have important implications for health and disease. In dairy cows, polymorphism of bovine major histocompatibility complex (BoLA) gene has been associated with susceptibility to several infectious diseases, most importantly mastitis. However, mechanisms underlying this association are yet poorly understood. In the present study, we sought to explore the association of BoLA gene polymorphism with the dynamics of mammary microbiota during the first week of lactation.ResultsColostrum and milk samples were collected from multiparous Holstein dairy cows at the day of calving and days 1 and 6 after calving. Microbiota profiling was performed using high-throughput sequencing of the V1-V2 regions of the bacterial 16S rRNA genes and ITS2 region of the fungal ribosomal DNA. Polymorphism of BoLA genes was determined using PCR-RFLP of exon 2 of the BoLA-DRB3. In general, transition from colostrum to milk resulted in increased species richness and diversity of both bacterial and fungal communities. The most dominant members of intramammary microbiota included Staphylococcus, Ruminococcaceae, and Clostridiales within the bacterial community and Alternaria, Aspergillus, Candida, and Cryptococcus within the fungal community. Comparing the composition of intramammary microbiota between identified BoLA-DRB3.2 variants (n = 2) revealed distinct clustering pattern on day 0, whereas this effect was not significant on the microbiota of milk samples collected on subsequent days. On day 0, proportions of several non-aureus Staphylococcus (NAS) OTUs, including those aligned to Staphylococcus equorum, Staphylococcus gallinarum, Staphylococcus sciuri, and Staphylococcus haemolyticus, were enriched within the microbiota of one of the BoLA-DRB3.2 variants, whereas lactic acid bacteria (LAB) including Lactobacillus and Enterococcus were enriched within the colostrum microbiota of the other variant.ConclusionOur results suggest a potential role for BoLA-gene polymorphism in modulating the composition of colostrum microbiota in dairy cows. Determining whether BoLA-mediated shifts in the composition of colostrum microbiota are regulated directly by immune system or indirectly by microbiota-derived colonization resistant can have important implications for future development of preventive/therapeutic strategies for controlling mastitis.