A multi-disciplinary approach is proposed that will develop new theory, methods, and applications to five significant problems in genetic analysis. The methods include mathematical modeling, statistical formulation, writing appropriate computer programs, development of estimation procedures, Monte Carlo simulation to explore the properties of the estimators, and applications to various sets of actual empirical data. The empirical data will deal with diabetes, high blood pressure, several sets of linkage data, Marfan syndrome, hereditary polyposis coli, Alzheimer and Huntington diseases, reinitis pimentosa, and Usher's syndrome. However, this proposal does not seek funding for the collection of these data. The fields of study involved are genetics, statistics, applied mathematics, epidemiology, clinical medicine and psychiatry. The strategic goals include developing methods of analysis tailored to the authentic details of common clinical diseases (as opposed to omnibus solutions thought suitable for universal application). The specific projects deal respectively with I. Development of models of certain classes of types of homeostatic processes especially adapted to the physiological properties of diabetes and hypertension and their genetic implications. II. Studies on the statistical application of certain models already investigated, to simulated and actual data. III. Exploration of systematic methods of unifying and reconciling data from various sources on the organization of the genome (multipoint linkage analysis, gene assignment, etc.) and a detailed exploration of their statistical properties. IV. A systematic study of the best use of data to estimate the prevalence of a chronic genetic disorder, the data being ascertained in various ways and from multiple lists. V. Analysis of dependence of penetrance (manifestation) of a Mendelian disorder on covariables, notably age, and the connection between the estimation of penetrance and life-table analysis.
| Murphy, E A (1990) Dynamics of quantitative homeostasis: VIII. Processes that oscillate finitely many times. Am J Med Genet 35:552-60 |
| Murphy, E A; Trojak, J E; Berger, K R et al. (1987) The bingo model. IV. The statistics of survivorship in the bingo-gamma model. Am J Med Genet 28:691-701 |
| Murphy, E A; Berger, K R; Trojak, J E et al. (1987) The bingo model of survivorship. V. The problems of conformation to the empirical evidence. Am J Med Genet 28:703-17 |
| Murphy, E A (1987) A geneticist's approach to psychiatric disease. Psychol Med 17:805-15 |
| Murphy, E A; Pyeritz, R E (1986) Homeostasis. VII. A conspectus. Am J Med Genet 24:735-51 |
| Murphy, E A (1986) The statistics of quantifiable homeostasis. I. Simple linear homeostasis. Am J Med Genet 25:581-93 |
| Murphy, E A; Trojak, J L (1986) The genetics of quantifiable homeostasis: I. The general issues. Am J Med Genet 24:159-69 |
| Murphy, E A (1985) The dynamics of quantifiable homeostasis. VI: Processes of fractional order. Am J Med Genet 21:385-94 |
