The goal of this project was to identify and characterize polymorphic markers spanning regions of the bovine major histocompatibility complex (BoLA) to analyze patterns of genetic variation and haplotype structure across diverse cattle breeds with various breed histories and selection pressures. Genetic markers that demonstrated sufficient levels of polymorphism, locus specificity, Mendelian inheritance, and the accurate typing of alleles across diverse haplotypes were chosen to define separate haplotype structures for the BoLA IIb and BoLA IIa-III-I regions and to evaluate breakpoints in linkage disequilibrium within the regions surrounding BoLA IIa-III-I. A total of 23 microsatellites, two SNPSTRs, 62 SNPs, and the alleles of three class IIa genes were selected for use in this study. These markers revealed eleven recombination events, low levels of recombination in BoLA IIa-III-I, a sharp break in haplotype structure in the region centromeric to class IIa, prolonged linkage disequilibrium in the extended class I region, strong conservation of BoLA IIa-III-I haplotype structure, BoLA IIa-III-I homozygous haplotype identity across seven different breeds of cattle, and a small number of common BoLA IIa-III-I haplotypes within the Angus and Holstein breeds. This work demonstrated that 52 SNPs from the Illumina 50K SNPchip could accurately predict BoLA IIa-III-I haplotypes. These 52 SNPs represent tagSNPs that can predict BoLA IIa-III-I genetic variation and could offer a cost-effective means for screening large sample sizes for haplotype/disease association studies in the future.

Thesis (M.S.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains vi, 48 p. : ill. Vita. Includes abstract. Includes bibliographical references (p. 25-47).

Thesis (M.S.)--Rochester Institute of Technology, 2005. / Typescript. Includes bibliographical references (leaf 45).

This work examines the ecological, social and genetic factors that predispose amphibians to infection. In the last 30 years many amphibian populations have declined due to infectious disease, although few researchers have studied the factors involved in mediating amphibian infection. My research is designed to explore some of these factors. I first examined the effects of crowding, kin composition (the relatedness of individuals in a group), and habitat complexity on the growth and survival of Xenopus laevis tadpoles exposed to the bacterial pathogen Aeromonas hydrophila. In tadpoles, stress, and in particular corticosterone, a hormone associated with stress, is known to inhibit growth. Crowding, kin composition, and habitat complexity have all been linked to tadpole growth. As corticosterone exposure is also linked to reduced immune function, I examined how these ecological factors influence tadpoles' disease resistance. Tadpoles exposed to the bacterium were significantly smaller and more likely to die than control tadpoles. Tadpoles reared only with siblings (pure sibship groups) were larger, less variable in size, and had lower mortality rates than tadpoles reared in mixed sibship groups. The size difference between pure and mixed sibship groups was greatest when they were exposed to the pathogen. Habitat complexity reduced size variation within tanks but did not affect mean tadpole size. Mixed kinship composition and high tadpole density can increase competition, reduce growth, and increase disease susceptibility. These results indicate that growth was inhibited by pathogen exposure but kin association may ameliorate this effect. The Major Histocompatibility Complex (MHC) is an integral part of the vertebrate adaptive immune system. To determine the importance of the MHC in conferring disease resistance in amphibians, I challenged X. laevis tadpoles, bearing different combinations of four MHC haplotypes (f, g, j, and r), with A. hydrophila in two experiments. Exposure to A. hydrophila affected the growth and survival of these tadpoles and that the MHC moderated these effects. Tadpoles with two MHC haplotypes (r and g) were susceptible to this pathogen and tadpoles with the other two haplotypes (f and j) were resistant. Heterozygous tadpoles with both susceptible and resistant haplotypes were always intermediate to either homozygotes in size and survival. These results demonstrate that MHC genotype plays a major role in determining the impact of bacterial pathogens on the growth and survival of X. laevis tadpoles. To test whether the effect of exposure to pathogens differs according to the similarity of the hosts I challenged tadpoles with natural levels of the microorganisms associated with different MHC genotypes by exposing the tadpoles to water preconditioned by adults of different MHC genotypes. If the pathogens are adapted to the MHC genotype of their hosts, tadpoles exposed to water from adults with which they shared MHC haplotypes would be more susceptible than those exposed to water from MHC-dissimilar adults. Alternatively, if the hosts are adapted to their pathogens tadpoles may be more resistant to pathogens from MHC-similar frogs than those from MHC-dissimilar frogs. I found that tadpoles exposed to water from MHC-dissimilar animals developed faster, but without increased growth, and were more likely to die than those exposed to water from MHC-similar animals. Furthermore, there was an optimal difference between the tadpoles’ and the donors’ MHC where tadpoles were sufficiently different to the donor to defend against its locally adapted pathogens, and sufficiently similar to not be exposed to especially virulent foreign pathogens. Finally, I present an inventory of bacteria found in the gut and skin (nonsystemic sites) and heart, muscle, and abdominal cavity (systemic sites) of captive frogs. I found several species of bacteria previously identified as amphibian pathogens and many bacteria in systemic sites that have not been considered pathogenic to amphibians. None of the frogs tested positive for the amphibian chytrid fungus, Batrachochytrium dendrobatidis. I discuss the potential importance of these species of bacteria as amphibian pathogens and as protective probiotics, using New Zealand frogs as a case study. In its sum, this work describes some of the factors that can affect amphibians’ ability to resist disease. I show that the genetic constitution of an individual, specifically in terms of the MHC, affects the impact of a disease, and so too does its social and ecological conditions, including the level of crowding, the kinship of its groupmates and the specific microbial challenges of its immediate environment. I also show that many of the factors linked to tadpole growth and development that are well described in other amphibians also affect Xenopus tadpoles.

No description available.

No description available.

The blue shark (Prionace glauca) is a highly migratory pelagic elasmobranch that inhabits ocean basins globally. As a result, this shark is exposed to intensive ocean exploitation by commercial target fisheries, by-catch and for recreational pursuits globally. This top predator is therefore at high risk of becoming overfished. Advances to current knowledge of genetic population structure and diversity of this species would provide vital information required to initiate co-operative management approaches. In this study, the major histocompatibility complex (MHC) class IIa and IIβ genes were successfully isolated and characterised from blue sharks. Phylogenetic trees of the class II genes showed three major clades; one of teleost fish, one of tetrapods and one of sharks. The MHC class IIβ gene exon 2 primers successfully amplified partial sequences in blue sharks from several global locations. Analysis of sequences using denaturing gradient gel electrophoresis (DGGE) suggested the assay resolved different sequences up to one basepair, making the assay potentially very useful with further development. The class II genes presented in this study show conflicting evidence for the presence of more than one class II locus. To explore inheritance patterns of MHC exon 2 diversity, a single blue shark litter (mother + 19 pups) was cloned and sequenced, revealing evidence to suggest the possibility of more than one locus for class IIβ. Statistical analysis of parasite loads and diversities from blue shark spiral valves revealed no definitive population structure, supporting global and North Atlantic mtDNA and microsatellites genetic analyses presented here. The size (fork length) of sharks was found to be potentially influential when modelled with individual microsatellite heterozygosity and fork length. International co-operation will be required to prevent this species becoming extinct from global marine ecosystems. Reductions in numbers could lead to reduced genetic diversity, decreased immunity and ultimately an 'unhealthy' population.

Being a dissertation presented in fulfilment of the requirements governing the degree of Masters of Science in the Faoulty of Medicine, University of the Witwatersrand / Recent investigations have shown enhanced or aberrant expression of major histocompatibility system (MHC) antigens on cells lines derived from human hepatocellular carcinoma (HCC) in vitro and HCC in vivo. ( Abbreviation abstract ) / AC2017

The major histocompatibility complex (MHC) is a chromosomal region encoding molecules controlling adaptive immune response in vertebrates. In farm animals, many associations between MHC loci and productivity traits including disease susceptibility have been described. However, current knowledge about the structure and function of the MHC in domestic animals, especially sheep, is very limited. Characterization of the sheep MHC may potentially facilitate breeding for enhanced disease-resistant animals through use of marker assisted selection. The main aim of this project has been to provide insights into the organization of the genomic content of the central region of the sheep MHC. The work described herein has utilized subcloning of a sheep BAC genomic library in conjunction with DNA sequencing to generate a map of the central region of the sheep MHC covering ≈700 kbp. Within this map the relative order and identity of twenty five recognized loci were established. For some loci the intergenic distances were also determined. The final map is the most accurate map of this region reported to date and shows a high degree of similarity to the analogous region of the human MHC. This work has been published and a copy of the paper is included in Appendix 1. During the course of this work detailed genomic sequences were obtained for several sheep central region loci. Complete nucleotide sequences were generated for the complement factor B locus (CFB) and the TNFα locus and a comparative analysis of these sequences confirmed their homology with other vertebrate orthologues. Extensive partial sequences for complement components C2 and C4 were also obtained and reported to GenBank. / In addition, a previously identified short tandem repeat locus designated BfMs believed to be in the CFB locus was mapped to an intron within the adjacent SKI2VL locus. Single nucleotide polymorphisms (SNPs) were identified by analysing homologous sequences from a minimum of five individual sheep. In total 33 SNPs were discovered distributed over eleven distinct loci. Allele frequencies for SNPs from ten of these loci were determined and reported for a panel of 71 sheep comprising 58 unrelated sheep from the Rylington Merino flock plus a further 13 unrelated parental animals from a three generation half sibling sheep pedigree. The availability of an independently confirmed pedigree constructed from a three generation half sibling sheep family permitted the identification by deduction of central region MHC haplotypes based on a panel of SNPs derived from 10 loci. This is the first reporting of haplotypes covering this region of the sheep MHC. Analysis of SNP panel genotypes in the cohort of 71 unrelated sheep using the expectation maximization algorithm permitted the prediction of a group of approximately 20 haplotypes, which accounted for more than 90% of the expected haplotype distribution. Four of these predicted haplotypes were also present in the known haplotype cohort deduced from the sheep pedigree. Analysis of pairwise linkage disequilibrium between SNP loci in the cohort of 71 unrelated sheep showed a centre-most region displaying relatively high levels of linkage disequilibrium which was bounded by two regions displaying more variable linkage disequilibrium. / It is hypothesised that this mid region of the central region of the sheep MHC may be a block like structure characterized by low recombination similar to those that have been widely described in the human and mouse genomes. The discoveries reported in this thesis provide a more accurate and detailed description of the central region of the sheep MHC together with a panel of SNPs, which reflect the diversity of this important genomic region which is known to be associated with immune responsiveness. The description, for the first time, of central region haplotypes provides a practical means of seeking candidate loci associated with disease resistance and productivity traits. The application of molecular techniques will enhance the rate at which the genomic composition of this region is elucidated and the work described in this thesis will contribute to final characterization of this important complex in health and disease.

Thesis (Ph. D.)--University of Chicago, Dept. of Biochemistry and Molecular Biology, 2002. / Includes bibliographical references. Also available on the Internet.