| Aging in mammals is a complex process encompassing a plethora of phenotypic changes. This thesis describes the development and implementation of a system for studying the genetics of age-dependent phenotypes using a reproducible population of genetically heterogeneous four-way cross mice. The system has been applied to several age-dependent immune phenotypes, assessed at two individual timepoints as well as by repeated measures, and to lifespan. The analyses include associations of phenotype to individual marker loci, intervals spanning markers, and finally to pairs of independently segregating markers. Significance of association is assessed by permutation analyses. Although several markers were identified in single marker searches, for several traits additional markers were identified only through analysis of all possible marker pairs. This system is sufficiently general so that it can continue to be used as a resource for studying the genetics of a variety of age-dependent traits. |
