IDENTIFICATION OF CHROMOSOMAL REGIONS ASSOCIATED WITH INFECTIOUS DISEASES IN CATTLE

Ricardo Zanella

Genetic selection for animals resistant or tolerant to a disease might yield new opportunities to improve profitability of the animal industry. Selection for animals that are able to defend themselves against pathogenic infection or animals that can tolerate infection might result in healthier and more profitable animals. In this dissertation I am reporting studies which were conducted to identify genetic regions associated with tolerance and susceptibility for Johne's disease, bovine respiratory disease (BRD) and bovine viral diarrhea (BVD) in cattle. Johne's disease is an incurable bacterial disease caused by infection with Mycobacterium avium subspecies paratuberculosis and accounts for annual losses of over $200 million in the dairy industry. Animals exposed to this pathogen can either become infected or tolerate the infection. In the current study we evaluated the infection status of the animals based on the presence of the bacteria in the animal tissue. Tolerance to Johne's disease was measured as the relationship between MAP fecal shedding and MAP tissue infection. We identified genetic markers associated with tolerance to Johne's disease using a single marker association analysis and haplotype tests. With this approach a region of 10.6 kb on BTA3 was refined as associated with Mycobacterium avium subspecies paratuberculosis tissue infection and a region of 6.5 kb on BTA15 was refined as associated with tolerance to Johne's disease. Further evaluation of the region associated with MAP tissue infection was carried out using Jersey and Holstein cows leading to the identification of a SNP that is part of the 3'UTR of the EDN2 and also part of a transcription binding factor for VDR, CXADR and NR1I2 with a possible involvement for susceptibility to MAP infection in cattle. Bovine respiratory disease (BRD) is a complex of diseases resulting from viral, mycoplasmal and bacterial pathogens and it is responsible for more than 29% of the cattle deaths in the beef industry in the U.S. Bovine viral diarrhea virus (BVDV) is the most costly viral disease spread worldwide and is one of the pathogens associated with BRD infection. Loci associated with BVD-PI and linked with BRD have previously been identified within 14 Mb on bovine chromosome 2 (BTA2) and 15.3 Mb on bovine chromosome 26 (BTA26). Using an allelic chi-square test, 11 loci on BTA2 and 8 loci on BTA26 were associated with the dams of the BVD-PI calves (P < 0.05). Associations (P < 0.05) with BVD-PI calves were identified with 5 loci on BTA2 and 10 loci on BTA26. One locus on BTA2 and two loci on BTA26 were found to be linked (P < 0.05) with BRD. Identification of genetic markers involved with susceptibility or tolerance to infectious disease may offer a new approach to select for animals that are healthier and more productive animals.

IDENTIFICATION OF CHROMOSOMAL REGIONS ASSOCIATED WITH INFECTIOUS DISEASES IN CATTLE

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