Pedigree Analysis for Genetic Counseling

We report on the design and implementation of a prototype program, GENINFER  , to assist genetic counselors in evaluating the risk of recurrence of genetic disorders based on the analysis of family pedigrees. The present version of the program integrates a convenient graphical interface that permits counselors to draw, examine and modify family pedigrees and to enter information relevant to risk analysis. It also includes a general-purpose Bayesian inference mechanism that permits the rapid calculation and display of probabilities of various genotypes, for the consultand and all other pedigree members. This is possible even in the presence of complex pedigrees with multiple consanguineous matings. The ability to support rapid calculation also enables the user to perform sensitivity analyses. Limitations of the prototype include a restriction to single-locus Mendelian disorders and an inability to make use of information from RFLP markers. Planned extensions include remedying these limitations, the incorporation of an algorithm for automated reformatting (layout) of an existing pedigree, improvements in the population genetic models used by the program, and connections to external databases for acquiring data on disease incidence, patterns of inheritance, mutation rates, penetrance, etc.