Year: 2007
Type: dissertation
Abstract: As life expectancy in the United States increases each year, the percentage of the\npopulation that is comprised of aged individuals rises also. Researchers expect the\nlargest increase in population to occur in the segment consisting of individuals 85 and\nolder. Thus, investigations of the aging process, with the goals of further extending\naverage life expectancy and improving the quality of life for aged individuals, have\nbecome increasingly important to our society.\nTo better understand the genetics of aging, we elected to utilize another model\norganism, the domestic dog. The benefit to this work is that breeds exhibit extreme,\nnatural variation in life expectancies. Here I report my contributions towards\nestablishing the dog as another model organism for investigations of the aging process.\nMultiple linear regression analysis was carried out to determine the association\nbetween life spans and breed size in the dog, based upon data derived from the American\npet population. A negative correlation was observed between both height and longevity\nand between weight and longevity with weight being the significant predictor of life\nspan. Fifty-four genes implicated in the aging process were mapped to the canine\ngenome. These genes were selected because of their demonstrated contribution to\nlongevity in other organisms or based upon their proximity to a marker, D4S1564, on\nhuman chromosome 4.\nFour genes that are associated with dwarf mice and extended life span were\nanalyzed in nine dog breeds of varying sizes and life expectancies. Fifty-three\npolymorphisms were discovered in Ghr, Ghrhr, Pit1, and Prop1. Thirteen ancestral\nSNPs were discovered in which both alleles were found in every breed. In Ghrhr, a\ntransition mutation was found that changes the amino acid sequence as well as the\nfunction of the protein and is statistically significant (p=4.8 x 10-6) when large dogs are\ncompared to medium-sized breeds, but not when they are compared to small breeds\n(p=0.001). This SNP warrants further investigation in additional dogs and breeds.
Author: Sarah C. Canterberry
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2271977345