Coordinated genetic control of neoplastic and nonneoplastic diseases in mice.
Some models of aging imply that late-life diseases, though roughly synchronous, are the result of distinct pathophysiological processes, each in turn influenced by polymorphisms at multiple loci. Other models suggest that the dramatic increase in later life of multiple forms of illness might reflect the outcome of a unitary process, of so-far unknown biochemical nature, that proceeds at a species-specific rate to increase the risk of many forms of disease and disability in parallel. We have previously reported the results of genetic linkage analyses documenting the ability of alleles at D9Mit110, D10Mit15, and D12Mit167, and an allele pair at D2Mit58 and D16Mit182 to predict longevity in mice bred as the progeny of (BALB/cJ x C57BL/6J)F1 mothers and (C3H/HeJ x DBA/2J)F1 fathers (the UM-HET3 stock). Here we report the results of post hoc analyses to test the hypothesis that the genes that extend the life span of mice dying of neoplastic diseases also extend the life span of mice that die of nonneoplastic causes. In all four cases we find that the genotype associated with increased survival in mice dying of cancer is also associated for a similar degree of life span extension in mice dying of other causes. For D9Mit110 and the combination of D2Mit58 and D16Mit182, the difference is statistically significant in both the neoplastic and nonneoplastic mouse groups. The data support the hypothesis that many forms of late-life disease may be influenced by shared pathophysiologic mechanisms that are under coordinated genetic control.
Miller
Richard A
RA
Department of Pathology, University of Michigan, Ann Arbor, USA. millerr@umich.edu
Chrisp
Clarence
C
Jackson
Anne U
AU
Galecki
Andrzej T
AT
Burke
David T
DT
D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D004194:Disease; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016678:Genome; D008136:Longevity / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000235:genetics / Q000401:mortality; D019655:Quantitative Trait, Heritable; D014570:Urologic Diseases / Q000235:genetics / Q000401:mortality