The free radical theory of aging postulates that aerobic activities within the cell produce reactive oxygen species which cause damage to macromolecules, an underlying factor in organismal aging (senescence). The molecular basis of the effect of increased oxidative stress on longevity, however, remains very little understood. Increasing our understanding of the biological basis of natural resistance to oxidative stress is the budgerigar, Melopsitaccus undulatus. The budgerigar is a flying bird that is characterized by an exceptional longevity despite a high metabolic rate and consequent exposure to oxidative stress. Additional rationale for using the budgerigar as a model species for studying the biology of aging include wide availability as a pet, extensive knowledge about its physiology and nutritional requirements as well as short breeding cycles and potentially large family sizes. Despite these, however, its use to investigate the molecular basis of certain mechanisms like oxidative stress is limited because of our poor knowledge of its genome. Such knowledge will facilitate the use of emerging tools of comparative genomics to identify the genes that underlie the budgerigar's exceptional resistance to oxidative stress. To begin to address this paucity in genomic information for the budgerigar, we propose in the present R03 project to develop resources and genomic reagents needed for the construction of a budgerigar genome map. The resources that will be developed include a backcross reference panel and DNA markers based on cross-species amplification of map-based chicken, quail and turkey markers. The resources developed will lead, in a subsequent R01 project, to the construction of the first genome map of a model organism with a strong gerontological interest. A map will be useful in applying the tools of reverse genetics to identify the genes that underlie resistance to oxidative stress in the budgerigar or to use comparative genomics with more closely related (compared to mammals) but short-lived birds, including the quail and chicken, to identify these genes. The project will permit the development of a coordinated and directed budgerigar genome-mapping project led by a geneticist with a strong background in avian genomics and a biologist with extensive experience in the use of animal models, including birds, in aging research.
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