THE PRIMARY GOAL OF THIS PROJECT IS TO IDENTIFY NATURALLY OCCURRING GENETIC VARIATION THAT IS EITHER STATISTICALLY PREDICTIVE AND/OR CAUSAL FOR IMPROVED RESISTANCE TO CLINICAL MASTITIS IN COMMERCIAL U.S. DAIRY COWS. CLINICAL MASTITIS IS CHARACTERIZED BY ABNORMALITIES IN THE MILK OR UDDER OF DAIRY COWS, WHICH NEGATIVELY IMPACTS DAIRY PRODUCTION, THEREBY TRIGGERING ECONOMIC LOSSES, AND DIMINISHED FOOD SECURITY. HEREIN, WE FOCUS ON CLINICAL MASTITIS THAT IS CAUSED BY ESCHERICHIA COLI, WITH E. COLI OFTEN BEING THE MOST COMMONLY ISOLATED BACTERIAL ORGANISM OBSERVED AMONG U.S. DAIRY COWS THAT EXPERIENCE SINGLE OR RECURRING EPISODES OF CLINICAL MASTITIS. RELEVANT ECONOMIC LOSSES IN THE U.S. HAVE BEEN REPORTED TO EXCEED 700 POUNDS OF SALEABLE MILK FOR A SINGLE COW EXPERIENCING CLINICAL MASTITIS, WHICH WOULD INCLUDE DIRECT PRODUCTION LOSSES, OR THE WITHHOLDING OF DRUG CONTAMINATED MILK (I.E., THERAPEUTIC TREATMENT) FROM THE MARKET. TO REDUCE NATIONAL DEPENDENCE ON THERAPEUTIC AGENTS (I.E., ANTIBIOTICS, ANTI-INFLAMMATORY DRUGS) WHILE ALSO ENHANCING DAIRY PRODUCTION, WE TAKE A NOVEL APPROACH WHICH SEEKS TO DEFINE NATURAL GENETIC VARIATION AMONG U.S. PRODUCTION DAIRY COWS AND THEIR E. COLI CLINICAL MASTITIS ISOLATES THAT EITHER JOINTLY OR INDEPENDENTLY ENHANCE THE RISK OF DISEASE. AT PRESENT, GENETIC DATA ARE ALREADY HEAVILY UTILIZED FOR ACCURATELY PREDICTING MANY DAIRY PRODUCTION TRAITS IN THE U.S., AND FORM THE BASIS FOR MODERN SELECTIVE BREEDING PROGRAMS (I.E., GENOMIC SELECTION). INFORMATION REGARDING NATURALLY OCCURRING GENETIC VARIANTS AMONG U.S. DAIRY COWS AND E. COLI BACTERIAL ISOLATES THAT ENHANCE RISK FOR CLINICAL MASTITIS WILL BE INCORPORATED INTO EXISTING U.S. DAIRY PREDICTION AND SELECTIVE BREEDING PROGRAMS. SELECTIVE BREEDING OF MORE RESISTANT U.S. DAIRY COWS IS ULTIMATELY THE MOST SUSTAINABLE APPROACH TO REDUCING DISEASE INCIDENCE AND ASSOCIATED PRODUCTION LOSSES, AS THESE COWS WILL POSSESS SUPERIOR PRODUCTION EFFICIENCY, REQUIRE LESS HANDLING, EXPERIENCE IMPROVED ANIMAL WELFARE, REQUIRE DECREASED USE OF THERAPEUTIC AGENTS (I.E., ANTIBIOTICS, ANTI-INFLAMMATORY DRUGS) AND ARE ULTIMATELY THE MOST PROFITABLE.