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INVESTIGATOR: Koltes, J.; Koltes, J. E.

PERFORMING INSTITUTION:
IOWA STATE UNIVERSITY
2229 Lincoln Way
AMES, IOWA 50011

A SYSTEMS GENETICS APPROACH TO IDENTIFY EPIGENETIC VARIANTS ASSOCIATED WITH SKELETAL MUSCLE NUTRIENT CONTENT

NON-TECHNICAL SUMMARY: Epigenetics is the study of mutations and mechanisms "above" the DNA code that fine-tune expression of genes and pathways. Epigenetic modifications of DNA are known to play a role in diabetes, obesity, skeletal muscle growth and development. Notable epigenetic mechanisms include imprinting (e.g. phenotype depending upon whether dam or sire was the source of the genetic effect), DNA methylation (inherited and environmentally regulated), and non-coding RNA such as microRNAs. The objective of this research proposal is to evaluate the potential relationship of microRNAs, and allele specific expression (a surrogate measure of DNA methylation and imprinting) with iron and fatty acid content in bovine skeletal muscle. The proposal uses a systems genetics framework, incorporating genetic information from multiple levels of control (genetic, transcriptional, and epigenetic) in the analysis of phenotypes. The utility of this research is both applied and basic in nature. This proposal will determine if epigenetic markers are important in livestock selection schemes to improve beef nutrient content, which would add value to the US beef industry. Epigenetic studies in livestock will also act as a model for human diseases such as obesity and hemochromatosis. A database and bioinformatic tools developed in this proposal will facilitate future livestock epigenetic research. Furthermore, this proposal addresses two USDA priority areas: 1) keep American agriculture competitive while ending world hunger; and 2) improve nutrition and end childhood obesity.

OBJECTIVES: The overall GOALS of this proposal include: 1) determining the association of epigenetic variants with bovine skeletal muscle nutrient content; and 2) providing faculty-in-training experiences. The following specific aims address the research objectives of this proposal. SPECIFIC AIM 1: Identify miRNA and allele specific expression (ASE) variants associated with total iron content and fatty acid content in skeletal muscle with divergent phenotypes. The objective of this aim is to find transcripts, miRNAs, ASE SNPs and networks that are associated with muscle iron content and fat traits (e.g. marbling, back fat, fatty acid profile). SPECIFIC AIM 2: Develop an online livestock community resource for the discovery and cataloguing of epigenetic variants. The objective of this aim is to develop a database to catalogue ASE variants, splice variants, non-coding RNAs, and methylated DNA in livestock. EXPECTED OUTPUTS: Completion of proposed research is expected to result in the discovery of transcripts, non-coding RNAs, ASE markers and pathways that are associated with iron and fat content in muscle as well as a public database of epigenetic variants in livestock. The accomplishment of these aims and additional professional development training will prepare Dr. Koltes for an independent, tenure-track faculty position.