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United States Department of Agriculture

Agricultural Research Service

Title: Integrated Genomic, Proteomic and Metabolomic Dissection of Polygenic Selection Response for Murine Growth and Fatness

Authors
item Pomp, Daniel - UNIV NEBRASKA, LINCOLN
item Jerez, N - UNIV NEBRASKA, LINCOLN
item Allan, Mark
item Eisen, E - NORTH CAROLINA STATE UNIV

Submitted to: World Congress of Genetics Applied in Livestock Production
Publication Type: Proceedings
Publication Acceptance Date: August 20, 2002
Publication Date: August 20, 2002
Citation: Pomp, D., Jerez, N., Allan, M.F., Eisen, E.J. 2002. Integrated genomic, proteomic and metabolomic dissection of polygenic selection response for murine growth and fatness. World Congress of Genetics Applied in Livestock Production. Session 19, Selection theory and experiments in farm and laboratory animals. CD-ROM Communication No. 19-11.

Interpretive Summary: Growth and fatness are highly complex traits, controlled by relatively equal contributions of genetic and environmental influences. In addition to clear agricultural relevance, these traits have large biomedical importance. For example, approximately 280,000 adult deaths in the US each year are attributable to obesity, and it is the single largest health risk, costing ~$100B/year through direct and indirect effects on heart disease, type-II diabetes, and related maladies. Understanding how such traits are regulated will greatly benefit development of diagnostic tests, therapeutic agents and targets for transgenic manipulation to enhance genetic improvement and management of agricultural animals. We have used a highly unique mouse model to study the genetic architecture of polygenic growth and fatness. The M16 line was the result of nearly 30 generations of selective breeding for large size, resulting in correlated responses of moderate obesity and several related diseases. We have extended previous evaluation of selection response in M16 to include products of metabolism and protein analysis and are including such phenotypes in a large-scale QTL analysis. In addition, we have created advanced genetic resources (congenic line, F2 intercross and recombinant F3s) to characterize and fine-map a previously identified region of M16 genome harboring QTL with large effects on growth and fatness, towards positional cloning of the underlying gene(s).

Technical Abstract: Growth and fatness are highly complex traits, controlled by relatively equal contributions of polygenic and environmental influences. In addition to clear agricultural relevance, these traits have large biomedical importance. For example, approximately 280,000 adult deaths in the US each year are attributable to obesity, and it is the single largest health risk, costing ~$100B/year through direct and indirect effects on heart disease, type-II diabetes, and related maladies. Understanding how such traits are regulated will greatly benefit development of diagnostic tests, therapeutic agents and targets for transgenic manipulation to enhance genetic improvement and management of agricultural animals. We have used a highly unique mouse model to study the genetic architecture of polygenic growth and fatness. The M16 line was the result of nearly 30 generations of selective breeding for large size, resulting in correlated responses of moderate obesity and several related maladies. We have extended previous evaluation of selection response in M16 to include metabolomic and proteomic analysis and are including such sub-phenotypes in a large-scale QTL analysis. In addition, we have created advanced genetic resources (congenic line, F2 intercross and recombinant F3s) to characterize and fine-map a previously identified region of M16 harboring QTL with large effects on growth and fatness, towards positional cloning of the underlying polygene(s).

Last Modified: 11/23/2014
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