This project proposes to (1) continue the theoretical development of statistical methods for genetic segregation and linkage analysis of human pedigree data, (2) continue development of standardized computer programs based on these theoretical developments, (3) develop a more extensive map of the human genome, (4) analyze family and pedigree data, and (5) maintain a computer system dedicated to genetic analysis. The development of new statistical methods for genetic segregation and linkage analysis stems from the Bonney-Elston algorithm, a recently developed multivariate extension to the Elston-Stewart algorithm. A recurrence formula has been derived that allows for the exact calculation of the likelihood of quantitative multivariate traits in simple and complex pedigrees under the oligogenic and/or polygenic models of inheritance. Additional methodological developments are proposed. A modularized program package, based on these new methods will be developed; all programs will be written in ANSI standard Fortran 77. To develop a more complete map of the human genome a polymorphism laboratory will be maintained and its capabilities extended to allow typing newer systems, using isoelectric focusing or other electrophoretic techniques; and these newer polymorphic systems will be determined on families that have been previously genotyped for 20-40 polymorphisms (the HGAR families). In addition, a comprehensive compilation of human linkage data will be produced in the form of a linear genetic map, combining the summary data from our own laboratory with that published by others. The HGAR families will be reanalyzed for linkage between the newer polymorphic markers and e.g. von Willebrand's disease, hypercholesterolemia, Tay-Sach's disease and traits associated with hypertension, using multivariate methods. And finally, the maintenance of a computer system dedicated to genetic analysis will provide for the practical application of these new statistical methods to pedigree data collected by other research workers, as well as the development of programs and the testing of these methods and programs in simulation studies.
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