Understanding genetics of aging: Canis familiaris model

Texas A&M University System, College Station TX

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The long-term objective of this research is to establish the canine as a model of human aging, which would be useful for the elucidation of mechanisms associated with aging for several reasons. Within the species, there is a naturally diverse range of life span from which to sample. Compared to the human, life span is short which will allow analysis of a young cohort without making unconfirmed estimates of reduced life span. Canis familiaris is particularly useful for genetic studies due to a lack of intrabreed heterogeneity, which is a problem often confounding linkage analyses in the human. It is quite possible that heterogeneous phenomena in the human can be more easily dissected by utilizing a model with similar, if not identical phenotype, yet fewer contributing genes. To this end, we propose the identification and genetic mapping of the canine orthologs of loci implicated in human aging, specifically genes within the region of marker D4S 1564 on human chromosome 4 (Puca, 2001). Identification of canine orthologs will allow their positioning on the integrated canine linkage-radiation hybrid map. FISH analysis will complete the mapping efforts and help to decipher the current paucity of data concerning homologous regions of human chromosome 4 to the Canine genetic map as well as define evolutionary breakpoints. Lastly, development of gene expression profiles utilizing canine oligo microarray chips will allow gene expression comparisons between dogs living extended lives verses those having naturally short life spans. [unreadable] [unreadable]