Immunogenetic analysis of the population structure of Duroc breed swine during acclimatization

The American Duroc pigs characterized by the specific immunogenetic structure and especially by the high level of B and Hp loci polymorphism, and by the amylase locus monomorphism as well. Immunogenetic analysis allows revealing changes in the genetic structure of the population induced by breeding and during adaptation.     

Immunogenetic aspects of a canine breeding colony

A colony of dogs was expanded by selective breeding to study the immunogenetic determinants coded for by the major histocompatibility complex (DLA). Polymorphic determinants were identified by alloantisera specific for DLA-A and B loci antigens and by the mixed lymphocyte culture (MLC) which defined alleles at the D locus. Thirteen families totaling 58 offspring were produced and typed for allelic determinants coded for by each of the three gene loci. Allelic segregation in a codominant manner occurred as expected and a recombinant between the A and B loci was detected. A number of animals were homozygous at one or more loci, thus providing genetically standardized animals as a source of typing cells, antigens, and sera to further study the immunogenetic details of DLA and for in vivo studies in transplantation biology.     

21个野生,培育及地方猪种免疫及生化遗传标记基因位点的遗传分化研究

分析了亚,欧,美,非２１个野生,培育及地方猪种４个免疫遗传标记基因位点（Ｅ,Ｆ,Ｇ,Ｌ系统）和３人生化遗传标记基因位点（Ｃｐ,Ａｍ和Ｔｆ）的遗传多态性,认为Ｅ＾ａｅｇ,Ｆ＾ａ,Ｔｆ＾ｃ基因在亚洲猪种与欧美猪种间存在显著差异,是亚洲猪种３个重要的遗传标记基因,根据Ｆ＾ａ基因频率在亚,欧,美,非猪种的变化规律分析了其基因流向特点,证明欧美猪的育种过程中利用了中国地方猪种的血缘,计算了所测猪种间的Ｎｅｉ     

Immunogenetic structure of the Ukrainian White Steppe species pig herd by frequency of complex genotypes in connection with some parameters of productivity

Studying of the structural organization of the gene pool considering frequencies of occurrence of complex genotypes in animals simultaneously by many loci of blood groups allows to better characterize immunogenetic parameters of populations and peculiarities of selection acting upon animals of different genetic classes. The data on presence of the optimum level of gene diversity and peculiarities of selection acting upon polymorphic systems of blood groups in the pig herd of Ukrainian Steppe White breed have been obtained. The results can be used for increasing efficiency of breeding.     

Genetic profile of alloxan-induced diabetes-susceptible mice (ALS) and-resistant mice (ALR)

Two inbred strains from a foundation stock derived from Crj: CD-1 (ICR) mice were established after more than 20 generations of full-sib mating, and by simultaneous selective breeding for developing and not developing diabetes after alloxan administration (45 mg/kg in males, 47 mg/kg in females). To elucidate the genetic background of the two inbred strains, i. e., alloxan-induced diabetes-susceptible (ALS) strain and alloxan-induced diabetes-resistant (ALR) strain, their biochemical genetic markers and immunogenetic markers were examined. 1) For both strains, investigation of biochemical genetic markers at 19 loci and immunogenetic markers at 11 loci revealed no variation in any gene within the same strain, showing to be homogeneous, thus indicating establishment of the inbred strains. 2) The two strains differed from each other at 2 loci of biochemical genetic markers and at 5 loci of immunogenetic markers. 3) The ALS and ALR strains can be regarded as new inbred strains derived from ICR mice. 4) The results show that the marker genes of the two strains are different at 7 loci, but it remains unclear whether or not these genes are involved in the difference between the two strains in susceptibility to alloxan.     

MiDAS—Meaningful Immunogenetic Data at Scale

Human immunogenetic variation in the form of HLA and KIR types has been shown to be strongly associated with a multitude of immune-related phenotypes. However, association studies involving immunogenetic loci most commonly involve simple analyses of classical HLA allelic diversity, resulting in limitations regarding the interpretability and reproducibility of results. We here present MiDAS, a comprehensive R package for immunogenetic data transformation and statistical analysis. MiDAS recodes input data in the form of HLA alleles and KIR types into biologically meaningful variables, allowing HLA amino acid fine mapping, analyses of HLA evolutionary divergence as well as experimentally validated HLA-KIR interactions. Further, MiDAS enables comprehensive statistical association analysis workflows with phenotypes of diverse measurement scales. MiDAS thus closes the gap between the inference of immunogenetic variation and its efficient utilization to make relevant discoveries related to immune and disease biology. It is freely available under a MIT license.     

Habitat split as a driver of disease in amphibians

Anthropogenic habitat disturbance is fundamentally altering patterns of disease transmission and immunity across the vertebrate tree of life. Most studies linking anthropogenic habitat change and disease focus on habitat loss and fragmentation, but these processes often lead to a third process that is equally important: habitat split. Defined as spatial separation between the multiple classes of natural habitat that many vertebrate species require to complete their life cycles, habitat split has been linked to population declines in vertebrates, e.g. amphibians breeding in lowland aquatic habitats and overwintering in fragments of upland terrestrial vegetation. Here, we link habitat split to enhanced disease risk in amphibians (i) by reviewing the biotic and abiotic forces shaping elements of immunity and (ii) through a spatially oriented field study focused on tropical frogs. We propose a framework to investigate mechanisms by which habitat split influences disease risk in amphibians, focusing on three broad host factors linked to immunity: (i) composition of symbiotic microbial communities, (ii) immunogenetic variation, and (iii) stress hormone levels. Our review highlights the potential for habitat split to contribute to host-associated microbiome dysbiosis, reductions in immunogenetic repertoire, and chronic stress, that often facilitate pathogenic infections and disease in amphibians and other classes of vertebrates. We highlight that targeted habitat-restoration strategies aiming to connect multiple classes of natural habitats (e.g. terrestrial–freshwater, terrestrial–marine, marine–freshwater) could enhance priming of the vertebrate immune system through repeated low-load exposure to enzootic pathogens and reduced stress-induced immunosuppression.     

Mamu-DQA1 allele and genotype frequencies in a randomly sampled breeding colony of rhesus macaques (Macaca mulatta)

We studied the allelic and genotypic distribution of the major histocompatibility class-II locus DQA1 observed in a random sample of Indian rhesus macaques (Macaca mulatta) from a major breeding facility in the United States. The DNA was isolated from whole blood samples collected between 1991 and 1994 from 65 Indian rhesus monkeys. Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP), which involves use of specific amplification of DQA1 exon 2 and subsequent restriction digestion of the 242-base pair fragment, was used to genotype the animals for the 20 known macaque (Mamu)-DQA1 alleles. Frequencies for four alleles (DQA1*240x, *2502, *2503 and *0102) differed significantly from those reported in a smaller sample of rhesus macaques from the German Primate Center. The modest genetic survey of Mamu-DQA1 genotypes presented here will be particularly useful in designing epidemiologic studies that investigate associations between immunogenetic background and disease susceptibility in macaque models of human disease.     

Clinical and immunopathological significance of chimerism in bone marrow and organ transplantations

Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisites to induce chimerism are immunosuppression, myeloablation or severe immunodeficiency of the recipients on one side and donor originated immuno-hematopoietic cells in the graft on the other. Special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion and various kinds of solid organ grafting. There are various methods to detect the type of chimera state depending on the immunogenetic differences between the donor and recipient. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of graft-versus-host disease (GVHD), and the rate of relapse. However, the most important contribution of the chimeric state is the development of graft versus leukemia (GVL) effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.     

Formation of a gene pool of miniature Siberian swine "Minisibs" and their use in medico-genetic research

The results of 35-year breeding of a new variety of laboratory animals for biological and medical studies, termed Minisibs (miniature Siberian swine), are summarized. Minisibs were obtained via hybridization between Swedish Landrace pigs, who have an epistatic white coat color, and black Vietnamese masked pigs of breed I, who have genes of dwarfism. Some genes of wild boars Sus scrofa scrofa and S. s. nigripes from Central Europe and Central Asia, respectively, were introduced to the Minisibs gene pool in order to strengthen the constitution, increase the general resistance, and improve the functions of the cardiac muscle and valves. The pigs were selected for a decrease in body weight and an increase in litter size over 15 generations. Immunogenetic and chromosomal polymorphisms were constantly monitored by Robertsonian translocations Rb 15/17 and Rb 16/17 introduced from boars. Long-term breeding produced a population of laboratory pigs with an average adult weight of approximately 60 kg, a litter size of seven to eight piglets, and quiet behavior. Most of animals used in selection were white, which is essential for radiobiological experiments and studies on skin histocompatibility. Introduction of chromosomal polymorphism to the minipig gene pool and long-term immunogenetic and cytogenetic monitoring made it possible to perform subchromosomal mapping of the loci of some blood-group systems associated with the loci controlling coat color, litter size, stress resistance and meat quality (halothane sensitivity), and histocompatibility. Minisibs have been successfully used in numerous biomedical studies and in therapeutic and surgical cardiology (for production of diagnostic sera controlling lipid metabolism and of biological prostheses of cardiac valves). The anatomical and physiological similarity of Minisibs to humans indicate that these animals may serve as donors of xenografts for orthotopic heart transplants to humans.     

(Lack of) genetic diversity in immune genes predates glacial isolation in the North American mountain goat (Oreamnos americanus)

The major histocompatibility complex (MHC) plays an important role in an organism's ability to respond to pathogens. Immunogenetic diversity is advantageous as it permits the recognition of more external antigens. For this reason, MHC and immune gene variation are considered a barometer for the genetic health of wild populations. Mountain goats (Oreamnos americanus) were previously shown to have little variation at the MHC Class II Oram-DRB locus, which was attributed to population bottlenecks during the last glacial maximum (LGM). In this paper, we extended the analysis of immunogenetic variability in mountain goats to 5 genes representing the 3 classes of MHC gene (Class I OLA, Class II DRA and DRB, and Class III TNF-α) and the natural resistance-associated macrophage protein. We sequenced approximately 3000 bp from 31 individuals sampled across the range of mountain goats and found very low levels of diversity (1-3 polymorphic sites per gene) with the exception of the Class I Oram-OLA gene. Oram-OLA was nearly 30 times more diverse than the other immune genes and appears to represent a source of increased immunogenetic diversity. This diversity may be attributed to multiple loci, mediated by pathogen exposure, or potentially influenced by social factors. The distribution of SNPs was not associated with refugial history, suggesting that the current distribution of immunogenetic diversity was present prior to the LGM. These data suggest that although they have low levels of diversity at the 4 of 5 immune loci, mountain goats may be better equipped for future climate oscillations and pathogen exposure than previously thought.     

Adaptive tolerance to a pathogenic fungus drives major histocompatibility complex evolution in natural amphibian populations

Amphibians have been affected globally by the disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis (Bd), and we are just now beginning to understand how immunogenetic variability contributes to disease susceptibility. Lineages of an expressed major histocompatibility complex (MHC) class II locus involved in acquired immunity are associated with chytridiomycosis susceptibility in controlled laboratory challenge assays. Here, we extend these findings to natural populations that vary both in exposure and response to Bd. We find that MHC alleles and supertypes associated with Bd survival in the field show a molecular signal of positive selection, while those associated with susceptibility do not, supporting the hypothesis that heritable Bd tolerance is rapidly evolving. We compare MHC supertypes to neutral loci to demonstrate where selection versus demography is shaping MHC variability. One population with Bd tolerance in nature shows a significant signal of directional selection for the same allele (allele Q) that was significantly associated with survival in an earlier laboratory study. Our findings indicate that selective pressure for Bd survival drives rapid immunogenetic adaptation in some natural populations, despite differences in environment and demography. Our field-based analysis of immunogenetic variation confirms that natural amphibian populations have the evolutionary potential to adapt to chytridiomycosis.     

Biochemical genetics and fishery management: an historical perspective

This paper traces the development of applications of biochemical genetic methods to problems of fishery management over a period of four decades. In the 1950s, details of presumed genetic structuring offish species appeared destined for revelation through Mendelian characters identified by immunogenetic procedures. In the 1960s, immunogenetic methods were displaced by protein electrophoresis, with a proliferation of reports of genotypic and allelic data for protein-coding loci. In the 1970s, disagreement about the biological significance of protein polymorphisms delayed acceptance of management applications of this variation. In the 1980s, management applications included identification of relationships among populations, analyses of mixed stock fisheries, and uses in fish culture, conservation biology and forensics. The complementary relationship between protein electrophoresis and nucleic acid technologies is stressed, with a plea to recognize the unique attributes of properly applied protein electrophoresis in fishery management.     

Gene pool of pig breeds in southern region of Ukraine as determined from immunogenetic parameters

On the basis of the long-term observations of 22 334 pedigree animals, the level of genetic polymorphism and basic breed-specific immunogenetic parameters were determined in eight major pig breeds from southern Ukraine. The high level of gene diversity was revealed and the degree of genetic similarity between the studied breeds was estimated.     

Gene Pool of Pig Breeds in Southern Region of Ukraine as Determined from Immunogenetic Parameters

On the basis of the long-term observations of 22 334 pedigree animals, the level of genetic polymorphism and basic breed-specific immunogenetic parameters were determined in eight major pig breeds from southern Ukraine. The high level of gene diversity was revealed and the degree of genetic similarity between the studied breeds was estimated.     

Preventing insulin dependent diabetes mellitus: the environmental challenge. Diabetes Epidemiology Research International.

The epidemiology of insulin dependent diabetes mellitus was evaluated to determine the degree to which the disease results from environmental agents and therefore might be prevented. The results of research indicate that insulin dependent diabetes can be produced in animal models by environmental factors, there are major geographical variations in diabetes, certain populations have shown rapid changes in incidence over time, migrants appear to take on the risk of diabetes in their new country, and certain viruses and chemicals cause insulin dependent diabetes in humans. The results of genetic and epidemiological studies also show that at least 60% of insulin dependent diabetes world wide, and perhaps over 95%, is environmentally determined and thus potentially avoidable. It is concluded that the primary worldwide determinants of diabetes are environmental not immunogenetic and that identifying and altering the diabetogenic environmental factor(s) are likely to be more effective and less risky in preventing insulin dependent diabetes than current immunogenetic approaches.     

Parasite-mediated selection drives an immunogenetic trade-off in plains zebras (Equus quagga)

Pathogen evasion of the host immune system is a key force driving extreme polymorphism in genes of the major histocompatibility complex (MHC). Although this gene family is well characterized in structure and function, there is still much debate surrounding the mechanisms by which MHC diversity is selectively maintained. Many studies have investigated relationships between MHC variation and specific pathogens, and have found mixed support for and against the hypotheses of heterozygote advantage, frequency-dependent or fluctuating selection. Few, however, have focused on the selective effects of multiple parasite types on host immunogenetic patterns. Here, we examined relationships between variation in the equine MHC gene, ELA-DRA, and both gastrointestinal (GI) and ectoparasitism in plains zebras (Equus quagga). Specific alleles present at opposing population frequencies had antagonistic effects, with rare alleles associated with increased GI parasitism and common alleles with increased tick burdens. These results support a frequency-dependent mechanism, but are also consistent with fluctuating selection. Maladaptive GI parasite ‘susceptibility alleles’ were reduced in frequency, suggesting that these parasites may play a greater selective role at this locus. Heterozygote advantage, in terms of allele mutational divergence, also predicted decreased GI parasite burden in genotypes with a common allele. We conclude that an immunogenetic trade-off affects resistance/susceptibility to parasites in this system. Because GI and ectoparasites do not directly interact within hosts, our results uniquely show that antagonistic parasite interactions can be indirectly modulated through the host immune system. This study highlights the importance of investigating the role of multiple parasites in shaping patterns of host immunogenetic variation.     

Cell surface antigens. IV. Immunological coorespondence between glycophorin and the a1 human cell surface antigen.

A stable human-Chinese hamster ovary cell hybrid has been produced which, in addition to the complement of Chinese hamster ovary (CHO-K1) chromosomes, contains only one human chromosome, No. 11. The human cell-surface antigens whose expression is controlled by human chromosome 11, and are expressed by this hybrid, have been defined as the AL immunogenetic complex. Although one component of this immunogenetic complex (a1) is also expressed by human red blood cells, a second component (a2) is not. Killing of an a1+ hybrid by anti-a1 serum and complement can be completely inhibited by glycophorin, the major glycoprotein component of the human erythrocyte membrane. In the presence of complement, antiserum prepared against glycophorin will kill only those cells which express a1. The anti-a1 killing activity of the anti-glycophorin can be absorbed out only by those cells which express a1. Therefore, it is concluded that the a1 cell-surface antigen has at least one antigenic component in common with glycophorin.