Studies in human genetics and cytogenetics

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

Denying intimacy: the role of reason and institutional order in the lives of people with an intellectual disability

This thesis explores differences in the ways that intellectually disabled people are perceived, interpreted and related to within a Western context. Through a comparison of familial and institutionalised forms of relatedness, it examines the interrelation between these differences and the consequences that they have for either denying or acknowledging severely intellectually disabled people's capacities for sociality. Drawing on Carrithers' (1992) concept of sociality and mutuality, and Wittgenstein's (1953) notion of language games, the thesis analyses the means by which a meaningful and shared existence with intellectually disabled people can be negotiated and developed. Although limited and restricted in their capacities for symbolic expression, such people do have modalities of symbolic life upon which sociality can be built. By analysing the symbolic practices utilised by my three profoundly intellectually disabled siblings, I seek to show how relationships across the difference of intellectual disability are able to be symbolically mediated and negotiated. I argue that it is necessary to engage in relations of mutual interdependence in order to even recognise and perceive these practices as purposeful and meaningful. The mutuality that ensues requires a level of intimacy, empathy and commitment that is not easily sustainable, but which is necessary for the maintenance of intellectually disabled people's existence as social beings. These intimate relations are contrasted with clinical and institutional forms of relatedness, both of which have been informed and shaped by a symbolic scheme of reason and normality. This symbolic scheme associates a capacity for reason with normal humanness, where reason is identified as particular abstract, linguistic, mental practices that are then deemed necessary for sociality. These are what intelligence tests measure, and it is through such assessments that intellectually disabled people are rendered asocial. The pathologising of intellectual disability as an abnormal embodiment, and the clinical tendency to search only for deficits in functioning and ability, has led to a denial or ignorance of intellectually disabled people's abilities to be the independent sustainers and authors of mutuality and sociality. I draw on my family's medical notes, records from the institution where two of my siblings were sent to live, as well as observations made during twelve months of fieldwork with a group of intellectually disabled people attending an activities centre, and either living in community group homes or with their families, to elucidate the ways in which such interpretations of intellectual disability become instituted into daily practice. The instituting of training and management practices within day centres, group homes and institutions for the intellectually disabled are a consequence of the perception that intellectually disabled people have no capacity for sociality as they are. So too are the legal and structural obligations that inform the forms of relatedness that staff have with the intellectually disabled people with whom they work. These relations are based on separation and disengagement rather than mutuality and intimacy. The aim in these institutionalised environments is to instil in such people a range of normative social, domestic and vocational skills as though it is upon these that their capacity as social beings are dependent. As a result, the symbolic practices and dispositional behaviours through which intellectually disabled people express themselves are not recognised as such, nor are they engaged with. This undermines intellectually disabled people's capacity to be joint contributors to social life in a way which incorporates their differences rather than trying to transform them

Relevance of pre-morbid cognitive impairment of schizophrenia

This thesis begins with an exploration of the historical associations between learning disability and schizophrenia, which leads to the modern supposition that schizophrenia is commoner in people with learning disability than the normal population. A critical evaluation of both community and hospital epidemiological studies indicates that the point prevalence of schizophrenia in people with mild learning disability is around 3% i.e. around three times that expected in the normal population. Five possible mechanisms to account for this increase are postulated and discussed: a chance co-occurrence, a common aetiology, an epiphenomenon, a severe schizophrenia and a 'de novo' disease

Some applications of genetics in dentistry

Genetics is fundamental to an understanding of differences between individuals and between populations. Common minor differences are found within what is generally accepted as the normal range of variation, while relatively unusual but more major differences may be appropriately considered under the heading of pathology. Both major and minor differences occur in terms of structure, function or susceptibility to disease. This submission contains examples of such differences and their exploitation or analysis, most of which fall within the general field of dentistry.A number of observations of inherited dental abnormalities in man and experimental animals are included. These indicate that there can be compensatory interaction between neighbouring tooth germs during development. Based on this interaction, a model to account for differential evolutionary reduction of tooth size is proposed. Studies of regional differentiation in the mouse vertebral column are described, the vertebral column being a series of homologous structures divided into morphological classes in the same way as heterodont dentitions. The effects of a number of inherited disorders of the axial skeleton indicate that vertebral class boundaries in the mouse are established at a very early stage, even before somite formation. The use of dental morphology for population discrimination is discussed in relation to studies of the genetics of dental morphological variation, and a population comparison in which the discriminating power of dental morphology was tested against that provided by known genetic variants.Studies of inherited iron-deficiency anaemia in the mouse are described. They show that the disorder is associated with thinner lingual epithelium than normal and possibly with increased susceptibility to oral candidosis. Different strains of Candida produced different levels of oral colonisation and infection in normal mice, suggesting that susceptibility to candidosis may be related to variation in the microorganism as well as the host. A human family study of Paget's disease of bone is reported. The results are consistent with the hypothesis that Paget's disease is caused by a common virus, with genetic variation for susceptibility to the disease. Also in man, a comparison between carriers of X-linked hypohidrotic ectodermal dysplasia (in whom manifestations of the disease may be limited to minimal hypodontia) and females with hypodontia for other reasons indicates that carriers may be distinguished from among female hypodontia cases in general by means of a reduced sweat pore count.In the past, various genetic principles have been misapplied in dentistry. Two critiques of such misapplications are included, together with contributions to a review of current dental research, undergraduate and postgraduate dental texts, and a major new medical genetics text

Guidelines for conducting birth defects surveillance

"In January of 1999, the National Birth Defects Prevention Network (NBDPN) established a Surveillance Guidelines and Standards Committee (SGSC) in order to develop and promote the use of standards and guidelines for birth defects surveillance programs in the United States. This set of guidelines is designed to serve as an important first step in the documentation of this process and as the vehicle for dissemination of the committee's findings. The Guidelines for Conducting Birth Defects Surveillance (henceforth referred to as The Surveillance Guidelines) were developed with three major long-term objectives in mind: To improve the quality of state birth defects surveillance data, including accuracy, comparability, completeness, and timeliness; To enhance the utility of state birth defects surveillance data for research on the distribution and etiology of birth defects; To encourage and promote the use of state birth defects surveillance data for the purposes of linking affected children with services and evaluation of those services. The technical guidelines that make up this document provide a way of improving the quality of birth defects surveillance data, which in turn enhances their use in support of the latter two objectives. Fundamental to quality is ensuring that procedures for all aspects of data definition, collection, management, and analysis are established and followed. Because state-based surveillance systems operate with different objectives and data needs, it is clear that, with respect to procedures and standards, 'one size does not fit all.' It is also clear, however, that common guidelines can provide a basis for the development of system-specific operating procedures and supporting manuals." - p. iIntroduction -- -- Chapter 1. The Whys and Hows of Birth Defects Surveillance - Using Data -- -- Chapter 2. Legislation -- Appendix 2.1. Sample State Legislation -- Appendix 2.2. Table of Birth Defects Legislation -- Appendix 2.3. Definitions Used to Determine Covered Entity Status Under the Privacy Rule -- Appendix 2.4. Office of Civil Rights (OCR) HIPAA Privacy Regulation Text -- -- Chapter 3.Case Definition -- Appendix 3.1. Birth Defects Included in the Case Definition of the National Birth Defects Prevention Network -- Appendix 3.2. NBDPN Abstractor's Instructions -- Appendix 3.3. Examples of Conditions Considered to Be Minor Anomalies -- Appendix 3.4. Conditions Related to Prematurity in Infants Born at Less Than 36 Weeks Gestation -- -- Chapter 4. Data Variables -- Appendix 4.1. Descriptions of Minimum (Core) Data Variables -- Appendix 4.2. Descriptions of Recommended Data Variables -- -- Chapter 5. Classification and Coding -- Appendix 5.1. Texas Disease Index -- Appendix 5.2. 6-Digit CDC Codes (updated 8/2007) -- -- Chapter 6. Case Ascertainment Methods -- Appendix 6.1. Data Source Described in Detail - Vital Records -- Appendix 6.2. Data Source Described in Detail - Hospital Data Sets -- Appendix 6.3. Data Source Described in Detail - Hospital and Patient Services Logs -- Appendix 6.4. Data Source Described in Detail - Genetic Services -- -- Chapter 7. Data Quality Management -- Appendix 7.1. Data Sources Descriptive Assessment Tool -- -- Chapter 8. Statistical Methods -- -- Chapter 9. Data Management and Security -- -- Chapter 10. Data Collaboration and Dissemination through the NBDPN -- -- Chapter 11. Data Presentation -- Appendix 11.1. Data Suppression -- Appendix 11.2. Use of Geographic Information Systems (GIS) to Map Data -- Appendix 11.3. Data Users Matrix -- Appendix 11.4. What Type of Chart or Graph Should I Use?edited by Lowell E. Sever."June 2004."Support for development, production, and distribution of these guidelines was provided by the Birth Defects State Research Partnerships Team, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention.Title from title caption (viewed on Jan. 6, 2012).Mode of access: Internet from the CDC web site as an Acrobat .pdf file ((7.6 MB, 627 p.).System requirements: Adobe Acrobat Reader.Includes bibliographical references.Text in PDF format.National Birth Defects Prevention Network (NBDPN). Guidelines for Conducting Birth Defects Surveillance. Sever, LE, ed. Atlanta, GA: National Birth Defects Prevention Network, Inc., June 2004

Die Autismusforschung und ihre neuere Entwicklung, ihre Bedeutung für den heilpädagogischen Unterricht sowie Falldarstelllungen und deren Bewertung

Forschungsergebnisse, Instrumente zur Erfassung des Autismus, Unterrichtung eines autistischen Kindes und weitere Falldarstellungen von Unterricht in verschiedenen Schularten