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This thesis embodies much of my work done over the past 25 years. The impetus for these studies was the need to provide the best tissue typing available for organ transplantation and to overcome the problems of defining HLA antigens in different ethnic groups. These goals were achieved by extensive international collaboration and participation in the International Histocompatibility Workshops. The discovery that the HLA antigens are associated with many diseases led to an epidemic of investigations in which over 500 diseases have been studied. In retrospect, it is not surprising that auto-immune diseases such as diabetes and rheumatoid arthritis showed such marked associations with HLA antigens. The studies in Part II of this thesis were aimed at finding out if the HLA associations reported in Caucasian populations were also present in the Black and Indian populations. These research interests led to my being invited by the National Science Council of the Republic of China in Taiwan to be a Visiting Professor at the National Taiwan University in Taipei for the 1989 academic year. I investigated the association between HLA and naso-pharyngeal carcinoma in Chinese during that year. I wish to express my appreciation to Dr Peter Brain who inspired the early investigations and continued to encourage and support my research. I am grateful to all my co-authors and the many colleagues, clinicians and laboratory staff who have contributed to the various research programmes. Studies of the relationship of the HLA system to cancer, diabetes, arthritis and other diseases have been supported in part by grants from the National Cancer Association and the Medical Research Council of South Africa. / Thesis (D.Sc.)-University of Natal, Durban, 1992.

Thesis (M. Phil.)--University of Hong Kong, 1997. / Includes bibliographical references (leaf 118-137).

Thesis (doctoral)--University of Uppsala, 1980. / Includes bibliographical references (p. 33-41).

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.

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.

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

published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 96-108).