THE DOMESTIC PIG IS IMPORTANT BOTH FOR AGRICULTURE AND HUMAN BIOMEDICAL MODELING. THE PORCINE GENOME ASSEMBLY HAS BEEN SIGNIFICANTLY IMPROVED. HOWEVER, THE LACK OF FUNCTIONAL ANNOTATION PREVENTS FULL EXPLOITATION OF SINGLE NUCLEOTIDE VARIANT ANALYSIS FOR GENETIC IMPROVEMENT THROUGH TRADITIONAL BREEDING, AND LIMITS EFFICIENCY OF GENE EDITING OF SPECIFIC GENOME COMPONENTS TO UNDERSTAND FUNCTION AND ACCELERATE GENETIC IMPROVEMENT.THE FUNCTIONAL ANNOTATION OF ANIMAL GENOME (FAANG) CONSORTIUM IS DEDICATED TO DEVELOPING THIS FUNCTIONAL INFORMATION FOR THE GENOME OF DOMESTICATED ANIMAL SPECIES, INCLUDING THE PIG. THE LONG-TERM GOAL OF THIS PROJECT IS TO CREATE A RESOURCE FOR UNDERSTANDING THE EXPRESSION AND REGULATORY FUNCTION OF EACH SEGMENT OF THE PORCINE GENOME ACROSS AND WITHIN DIVERSE BIOLOGICAL STATES. THIS RESOURCE WILL IMPROVE GENOME-WIDE GENETIC VARIATION ANALYSES THROUGH FILTERING OF VARIANTS ASSOCIATED WITH IMPORTANT PHENOTYPES. IDENTIFYING SUCH GENOTYPE-PHENOTYPE RELATIONSHIPS WILL INCREASE OUR ABILITY TO PREDICT PHENOTYPE FROM GENOTYPE, A CRITICALLY IMPORTANT GOAL IN ANIMAL GENETIC IMPROVEMENT. FUNCTIONAL ANNOTATION WILL ALSO IMPROVE SELECTION OF GENOME POSITIONS FOR GENE EDITING FOR GENETIC IMPROVEMENT AND BIOMEDICAL MODELING. WE PROPOSE TO DRAMATICALLY INCREASE THE DEPTH AND BREADTH OF CURRENT DATA ON THE FUNCTION OF EACH REGION OF THE PORCINE GENOME. WE WILL ALSO GENERATE A COMMUNITY RESOURCE FOR SCIENTISTS IN BOTH THE PUBLIC AND PRIVATE SECTORS TO ACCESS THIS DATA. ACROSS ALL OBJECTIVES, WE WILL USE RNA ASSAYS TO DIRECTLY MEASURE DIFFERENT COMPONENTS OF GENE EXPRESSION INTO RNA AND THE STRUCTURE OF THE CHROMATIN USING A RANGE ASSAYS TO ANNOTATE A TREMENDOUS BREADTH OF BIOLOGICAL STATES. IN OBJECTIVE 1, WE WILL APPROXIMATELY TRIPLE THE NUMBER OF ADULT TISSUES CURRENTLY BEING ANNOTATED. IN OBJECTIVE 2, WE WILL ANNOTATE FOUR TISSUES AT IMPORTANT STAGES OF FETAL DEVELOPMENT, AND LINK ALLELE-SPECIFIC EXPRESSION WITH ALLELE-SPECIFIC CHROMATIN MODIFICATIONS THROUGH ANALYZING DIVERGENT-BREED RECIPROCAL CROSSES. IN OBJECTIVE 3, WE WILL ANNOTATE CIRCULATING WHITE BLOOD CELL POPULATIONS IN HEALTHY PIGS, AS WELL AS MACROPHAGE RESPONSES TO BACTERIAL AND VIRAL MIMICS. WE WILL ALSO PROFILE GENE EXPRESSION OF SINGLE CELLS IN COMPLEX CELL POPULATIONS FROM IMMUNE TISSUES TO MAXIMIZE ANNOTATION OF THESE CRITICAL TISSUES. IN OBJECTIVE 4, WE WILL USE ALL THESE DATA AS WELL AS PUBLIC FAANG DATA TO GENERATE A FIRST-GENERATION CHROMATIN STATE SEGMENTATION MAP.COMPLETION OF THESE OBJECTIVES WILL GREATLY EXPAND OUR FUNCTIONAL KNOWLEDGE OF THE PORCINE GENOME, AND CREATE AN IMPORTANT RESOURCE FOR AGRICULTURAL AND BIOMEDICAL RESEARCH.
$2,500,000FY2018National Institute of Food and AgricultureUSDA
Iowa State University Of Science And Technology