Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2006. / On t.p. "+" is superscript. Includes bibliographical references (leaves 107-131). Also available in electronic version.

Thesis (M.S.)--Georgia State University, 2006. / Title from title screen. Susanna Greer, committee chair; Delon Barfus,Yuan Liu, committee members. Electronic text (72 p. : ill.) : digital, PDF file. Description based on contents viewed Aug. 20, 2007. Includes bibliographical references (p. 69-72).

Genome-wide association (GWA) studies confirmed that the HLA genes were strongly associated with schizophrenia but the HLA variants identified by GWA studies had a lower frequency in patients with schizophrenia than control subjects. The HLA molecules have function of presenting peptide antigens to T lymphocytes in order to initiate an immune response. Environmental factors such as infection and dietary proteins have been found to be associated with schizophrenia. This PhD program has thus focused on the following objectives: (1) identification of genetic variants for schizophrenia in the HLA region and (2) investigation of circulating antibodies to linear peptide antigens derived from wheat gluten in schizophrenia. The major findings from this work are as follows: 1. The HLA-DQ2.5 variants were strongly associated with schizophrenia; this finding is consistent with that from GWA study. 2. The NOTCH4 association was replicated in our study samples, in which a CNV in exon 19 of the gene may be associated with risk of schizophrenia. 3. There was no HLA-II variant identified to be associated with a high risk of schizophrenia but a CNV present in the HLA-DQ/DR region might confer risk of the disease. 4. The levels of circulating antibodies to linear peptide antigens derived from wheat gluten were significantly lower in schizophrenia patients than controls. This finding is inconsistent with previous studies that showed elevated levels of circulating antibodies in schizophrenia across subpopulations. In conclusion, it is likely that not one but many HLA variants lead to risk of schizophrenia development. From this research it is likely that anti-gluten antibodies are not an environmental trigger for this disease. Further investigation is needed to clarify the role of the HLA region in bridging the gap between genetic make-up and environmental factors in developing schizophrenia.

No description available.

The major histocompatibility complex of the rat (RT1 complex) encodes two sets of class II molecules referred to as RT1 B and RT1 D. The RT1 Bα gene was isolated from a Sprague-Dawley (RT1b) rat genomic library using a rat RT1 Bα chain cDNA as a hybridization probe. The coding and the majority of the intron DNA sequence was determined. The structure of the RT1 Bα gene is equivalent to that of H-2 and HLA a chain genes. Comparison of the nucleotide and predicted amino acid sequences of the RT1 Bα gene to those of the H-2 and HLA genes revealed a high degree of overall sequence conservation. However, two regions of the first external domain (a1), residues 19-23 and 45-78, exhibit marked sequence variation. Two blocks of conserved nucleotide sequence were identified in the 5' promoter region of the RT1 Bα gene that have been described in all MHC class II genes sequenced to date. These conserved sequences may be involved in the co-ordinate regulation of expression of class II genes. The cloned RT1 Bα gene was efficiently transcribed when transfected into mouse L cells. / Medicine, Faculty of / Medical Genetics, Department of / Graduate

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 144-157).

Development of techniques for observing variability at the major histocompatibility complex (MHC) of fishes could prove an important first step in understanding the genetic bases of disease resistance. In this study, using goldfish (Carassius auratus) as a model system, three approaches to generating antisera to putative MHC molecules and two methods for detecting antibody reactivities were evaluated. Seven full-sib families were produced, and red blood cells (RBCs) of goldfish family members were screened for reactivity with a panel of absorbed antisera. The antisera panel consisted of fish anti-fish, chicken anti-chicken, and chicken anti-fish antisera. The fish anti-fish antisera was produced by injecting RBCs from each parent into its mate, and the chicken anti-fish antisera was produced by injecting parental goldfish RBCs into chickens. The chicken anti-chicken antisera were obtained from a genetics laboratory where MHC-specific antisera had been prepared previously. The pattern of presence or absence of agglutination upon mixing with the respective reagents in this panel of antisera was regarded as the phenotype of the individual tested. Agglutinations observed macroscopically or microscopically were easily scored as positive or negative. Particular phenotypes were observed among individuals both within and between families. The large numbers of phenotypes observed may indicate: (1) the need for additional absorptions in the preparation of antisera, or (2) segregation of additional sets of phenotypic MHC haplotypes in the tetraploid goldfish. The utility of chicken anti-chicken reagents in serotyping of fish was demonstrated. Use of the traditional approach to conducting hemagglutination assays limited the number of assays executed because of the amount of blood required. In order to minimize the sample volumes required, antibody reactivities were evaluated by flow cytometry employing appropriate fluorescein labeled antibodies. Using this approach, scoring of positive and negative results was equivocal, and results did not always agree with those scored by hemagglutination assays. Results of this study strongly suggest that the development of immune allo- and xeno-antisera and use of hemagglutination assays can be used to characterize genetic variability of the MHC of fishes. Understanding of immunogenetic variability in fishes could be used to develop strains resistant to economically important fish pathogens. / Master of Science

Parasitism is one of the most common ways of living and it has arised in many taxa. Parasites feed and live inside or on their hosts resulting in both long and short term consequences for the host. This thesis is exploring the phenotypic and genotypic effects of animals living with parasitic infections. I have been studying three different parasite groups and their associated host species: the great snipe, a lekking freshwater wader bird that migrates between Africa and Northern Europe; the tree sparrow, a stationary passerine found close to human settlements and lastly the water vole, a large rodent living in riparian habitats. Avian malaria is one of the most commonly studied parasites affecting birds. Atoxoplasma, an intestinal protozoan parasite is less studied but is thought to be endemic in free-ranging birds. Given the freshwater habitat great snipes inhabit, a prevalence of 30% avian malaria infections is not high and that the prevalence fluctuated among years. Sequencing of the avian malaria cytochrome b gene revealed that parasites are similar to avian malaria parasites found in African birds suggesting that they were infected on the wintering grounds in Africa. Tree sparrows had few malaria infected individuals, a result that is consistent with other studies of stationary birds at high latitudes. Atoxoplasma infections were common in tree sparrows and capture-recapture analyses show decreased survival in infected compared to uninfected birds and signs of lower mating success among infected. Genetic analyses comparing the transcriptome between mated and unmated great snipe males revealed that the genotype is important for mating success and health status for some of the expressed genes. That variations in some of these genes are involved in maintaining a good health status and mating success supports handicap models for sexual selection in this lek mating system. The major histocompatibility complex (MHC) is a part of the immune system and it contains genes involved in immune response. In water voles, a number of new MHC alleles were identified. Based on their in silico phenotype they were grouped into supertypes to facilitate studies on how helminth infections affect the MHC diversity in the water voles. Some of these MHC supertypes provided resistance to one helminth species, but the same supertype caused the opposite effect for other helminth parasites. Overall, parasites are a driving force for maintaining genetic diversity and parasite infections lowers survival rate, which would lead to a lower lifetime breeding success.

The Major Histocompatibility Complex class II B (MHC II B) gene encodes a protein that is part of the adaptive immune system and critical for the non-self recognition ability of immune cells. This gene has been characterized in the Bald Eagle, ten unique alleles were found in two subpopulations at the geographic extremes of the range margins. Geographic genetic variation is suggested by the presence of population specific alleles. The results showed considerable divergence of groups of Bald Eagle alleles when compared to alleles from other birds of prey. Particular codons within the exon II show signs of balancing selection driving the evolution of the MHC II B. Transcription data showed statistically significant differential expression of alleles. This can be interpreted as meaning a particular locus is being preferentially expressed in blood. The analysis of the polymorphism of this adaptive marker may aid managers of wildlife during this age of global climate change and the biodiversity crisis. / by Andrew Smith. / Thesis (M.S.)--Florida Atlantic University, 2010. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2010. Mode of access: World Wide Web.

Infectious disease is a major issue facing the livestock industry. Further understanding of the role of genetic factors in the observed phenotypic variability of the immune response to pathogens and vaccination could assist in designing improved preventative measures such as more efficacious vaccines and targeted breeding strategies to select for disease resistance. Major candidate genes for controlling immune responsiveness are located within the major histocompatibility complex (MHC). The highly polymorphic classical MHC genes are key determinants in the strength and type of immune response. However, it has proved difficult to establish genotyping approaches to define functionally relevant allelic variations for outbred species such as cattle, not least because the peptide binding clefts (PBC) of classical MHC molecules are highly polymorphic, and the genes within the MHC complex are closely linked. The overall aim of this project was to investigate the role of MHC genes in immune responsiveness in approximately 200 F2 and backcross Holstein-Charolais cattle. These animals were generated as part of the Roslin Bovine Genome (RoBoGen) herd, established through a quantitative trait loci (QTL) project, in which a number of phenotypic traits including immune traits were measured. The immune traits included responses to a Foot-and-mouth disease virus (FMDV) peptide, and vaccines against bovine respiratory syncytial virus (BRSV), para-influenza virus 3 (PIV-3) and bovine herpes virus-1 (BHV-1), as well as T cell response to Staphylococcus aureus. The immune phenotypes measured included IgG and interferon- (IFN- ) levels and T cell proliferation. The cattle MHC region, known as bovine leukocyte antigens (BoLA), resides on bovine chromosome 23. The BoLA region contains approximately 200 genes most of which are immune-related. Class II gene polymorphisms were considered to be the most likely to influence the immune traits measured, and the project primarily focused on the best defined gene, BoLA-DRB3. A sequence-based typing technique was successfully improved to facilitate genotyping of the PBC of BoLA-DRB3 in all generations of the RoBoGen herd (approximately 400 animals) and identified 24 distinct alleles. The sequence information obtained also enabled further analysis of the role of defined ‘pockets’ within the PBC, which directly determine peptide binding affinity. All datasets were statistically analysed using a residual maximum likelihood (REML) model and it was shown that several of the DRB3 alleles within the RoBoGen herd had highly significant (p<0.05) associations with the immune response to the FMDV peptide. In addition DRB3 alleles were identified which had significant associations with the response to the respiratory pathogen vaccinations and exposure to S. aureus. The pocket analysis also enabled the identification of several amino acid positions within the PBC which were significantly associated with the immune response traits. In order to explore whether DQ Class II gene polymorphisms also played a role in the variability of responses and whether BoLA Class I-Class II haplotypes could be discerned, microarrays which utilized allele specific oligonucleotides for BoLA Class I and Class II DQ genes were employed. In addition, to investigate whether the number of DQ gene pairs per chromosome influenced the responses, a quantitative polymerase chain reaction (qPCR) assay to determine DQA gene dosage was developed. However, due to the extremely complex nature of the BoLA region both, techniques would require improving to be used for large-scale studies. Nonetheless, information about haplotypes was determined from the microarray results and the qPCR technique lays the foundations for future development to investigate DQ gene dosage. The MHC region in cattle is very complex due the high level of polymorphisms and gene duplications. It is likely that many genes play a role in the immune response to both pathogens and vaccines. However, from the evidence presented here, polymorphisms in the PBC of BoLA-DRB3, particularly within the pockets, are significantly associated with variation in immune response to many different antigens and this information could be exploited in the design of vaccines or breeding cattle for improved disease resistance.