Studies in human genetics and cytogenetics

Abstract

This thesis consists of 85 publications, of which 21 have been submitted for other degrees and are only included for completeness, leaving 64 assessable works. These fall into four broad categories, population cytogenetics, clinical genetics and cytogenetics, studies on amniotic fluid and prenatal diagnosis, and studies of heritable fragile sites on human chromosomes.The section on population cytogenetics includes most of the Australian studies on XYY males, epidemiological studies on Down syndrome in Australia and studies on the cytogenetics of paediatric necropsies. The clinical cytogenetics section mainly contains clinical case reports, which include a description of one of the first recognised insertional translocations in man, an important paper on trisomy 9 and one of the first discussions of genetic counselling of pericentric inversion carriers. This section also includes papers on gene mapping, alpha-1- antitrypsin phenotypes in chromosome abnormalities with descriptions of a new alpha-1-antitrypsin allele and studies on sister chromatid exchange in various groups of individuals with the documentation of an increase in this phenomenon in patients with multiple sclerosis.The section on prenatal diagnosis includes studies of the enzymology of amniotic fluid and cultured amniotic fluid cells, the discovery of rapidly adhering cells in amniotic fluid and documentation of their increased numbers in amniotic fluid surrounding fetuses with neural tube defects, and studies of chromosomal mosaicism in cultured amniotic fluid cells.The most important section of this thesis is the final one on studies of heritable fragile sites on human chromosomes. This section documents the discovery of the tissue culture requirements for the expression of fragile sites in lymphocyte culture, the finding of several new folate sensitive fragile sites and the co-discovery of the BrdU requiring fragile site at 10q25. Contributions to establishing fragile X-linked mental retardation as the second commonest genetic cause of mental retardation after Down syndrome, and population cytogenetic data for fragile sites are presented. Genetic linkage studies with fragile sites have established that a fragile site is coded for at the locus of the fragile site. Micronucleus studies have suggested that the folate sensitive fragile sites might be special examples of chromosome damage due to deprivation of DNA precursors.