ANIMAL HEALTH IS IMPORTANT FOR THE DAIRY INDUSTRY REGARDING PROFIT, SUSTAINABILITY, LABOR, ANIMAL WELFARE, AND CONSUMEREXPECTATIONS. MASTITIS AND OTHER CATTLE DISEASES DIRECTLY COST 230 MILLION DOLLARS EACH YEAR TO THE U.S DAIRY INDUSTRY. ALTHOUGHGENETICS PLAYS A RELATIVELY SMALL ROLE REGULATING DISEASE RISK, GENETIC AND GENOMIC SELECTION PROVIDES AN ECONOMIC ANDSUSTAINABLE WAY TO IMPROVE CATTLE HEALTH. SIX COMMON DISEASES INCLUDING MASTITIS HAVE BEEN INCLUDED IN THE NATIONAL GENOMICEVALUATION IN 2018, GENERATING LARGE VOLUME OF DATA FOR CATTLE HEALTH. THE OVERALL GOAL OF THIS PROJECT IS TO UNCOVER THE GENETICMECHANISM OF HOST RESISTANCE TO MASTITIS AND TO APPLY THESE GENOMIC DISCOVERIES TO IMPROVE CATTLE DISEASE RESISTANCE ANDPROFITABILITY OF THE DAIRY INDUSTRY. SPECIFIC AIMS ARE TO: 1) FIND GENOMIC REGIONS AND CANDIDATE GENES ASSOCIATED WITH MASTITIS BYUSING BIG DATA GENOME-WIDE ASSOCIATION STUDY (GWAS) OF MASTITIS AND OTHER IMMUNE-RELATED DISEASES; AND 2) INTEGRATESEQUENCE-LEVEL GWAS, TRANSCRIPTOME AND FUNCTIONAL VALIDATION OF IMMUNE CELLS TO IDENTIFY HEALTH SNPS AND APPLY THEM TOOPTIMIZE GENOMIC SELECTION OF DISEASE TRAITS. LEVERAGING THE US DAIRY GENOMICS DATABASE AND OTHER RESOURCES, OUR BIG-DATAGENOMIC INVESTIGATION AND APPLICATION WILL REVEAL THE GENETIC BASIS OF DISEASE RESISTANCE AND DELIVER A SET OF HEALTH SNPS TO THEDAIRY INDUSTRY TO IMPROVE THE SELECTION OF ROBUST CATTLE. THIS PROJECT WILL BE THE LARGEST SUCH GENOMIC STUDY OF DISEASE RESISTANCEIN DAIRY CATTLE AND IS EXPECTED TO HAVE A MAJOR IMPACT TO THE DAIRY INDUSTRY ON BOTH PROFITABILITY AND ANIMAL HEALTH.