This application proposes to continue to develop and distribute easy-to-use, powerful, and versatile software for likelihood analysis of family data by extending and enhancing PAP (Pedigree Analysis Package), a software package for the likelihood analysis and phenotype simulation of family data. One of the many applications of PAP, linkage analysis that is used to localize a gene within the genome, is the vital first step in the process of identifying a gene which underlies a disease. Present methods of linkage analysis require excess computer time and lack power when the disease inheritance pattern is complex. This application proposes to remedy both shortcomings. The first specific aim of this project proposes to develop, implement, and evaluate new genetic models and methodology in PAP. The general emphasis of this aim is to improve the multipoint linkage analysis methodology within PAP, by adding methodology to analyze complex traits and to make more efficient use of multipoint genetic marker data. Completion of this project will enable PAP to perform time-efficient multipoint linkage analysis either assuming or maximizing on any genetic model currently available in PAP, or using a mode-of-inheritance-free method. The second specific aim of this project proposes to enhance and support PAP. In addition to continuing to support and distribute PAP, this aim proposes to improve the portability of PAP by converting the source code from Fortran 77 to C++ and proposes to improve the ease-of-use of PAP by developing a graphical user interface. The software will be revised with particular consideration for the speed of computation, ease of use, and portability. A graphical user interface and web-based documentation will facilitate ease of use. The software will be made available through a web site allowing potential users to obtain a copy at no charge and with no delay. Questions will be answered promptly when problems of usage arise.
