A whole genome association analysis identified loci associated with Mycobacterium avium subsp. paratuberculosis infection status in U.S. Holstein cattle

Authors: SETTLES, M - Washington State University; ZANELLA, R - Washington State University; MCKAY, S - University Of Missouri; SCHNABEL, R - University Of Missouri; TAYLOR, J - University Of Missouri; WHITLOCK, R - University Of Pennsylvania; SCHUKKEN, Y - Cornell University; Van Kessel, Jo Ann; SMITH, J - University Of Vermont; NEIBERGS, H - Washington State University

Submitted to: Animal Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/15/2009
Publication Date: 4/24/2009
Citation: Settles, M., Zanella, R., Mckay, S.D., Schnabel, R.D., Taylor, J.F., Whitlock, R., Schukken, Y., Van Kessel, J.S., Smith, J., Neibergs, H. 2009. A whole genome association analysis identified loci associated with Mycobacterium avium subsp. paratuberculosis infection status in U.S. Holstein cattle. Animal Genetics. http://dx.doi.org/10.1111/j.1365-2052.2009.01896.x

Interpretive Summary: Johne’s disease is an infectious disease of cattle caused by the bacterium, Mycobacterium avium subsp. paratuberculosis (Map). A large number of US dairy herds are infected with Map and the dairy industry incurs large economic losses as a result of Johne’s disease. There is often a very long lag between the initial infection of a cow with Map and the onset of visible Johne’s disease symptoms; infected cows can harbor Map in their tissues without shedding the organism in their feces. The purpose of this study was to identify areas on chromosomes associated with Map infection status in US Holsteins using the Illumina BovineSNP50 BeadChip whole genome single nucleotide polymorphism (SNP) assay. Two hundred forty-five cows from dairies in New York, Pennsylvania and Vermont were followed until they were removed from their herds between January 1999 and November 2007 and subsequently were assessed for the presence of Map in fecal samples, lymph nodes, and intestinal tissue. Each animal was genotyped and after quality assurance filtering, 218 animals and 45,683 SNPs remained. We sought to identify genomic regions associated with four different case/control classifications: presence of Map in the tissue, presence of Map in feces, presence of Map in both tissue and feces and presence of Map in tissue but not feces. A case-control genome wide association study was conducted to test the four different classifications of Map infection status when compared to a Map negative control group. Regions on chromosomes 1, 5, 7, 8, 16, 21 and 23 were identified that showed a moderate significance or association with Map infection. Regions on chromosomes 3 and 9 were identified with a high level of association to the presence of Map in tissue and both tissue and feces, respectively. Identification of chromosomal regions associated with Johne’s disease in cattle is a first step in understanding the genetics of host resistance to this disease and in perhaps controlling the disease through selective breeding.

Technical Abstract: The purpose of this study was to identify loci associated with Mycobacterium avium subspecies paratuberculosis (Map) infection status in US Holsteins using the Illumina BovineSNP50 BeadChip whole genome SNP assay. Two hundred forty-five cows from dairies in New York, Pennsylvania and Vermont were followed to culling between January 1999 and November 2007 and subsequently were assessed for the presence of Map in both fecal samples and necropsy tissue. An animal was considered tissue infected if any sample contained at least one colony-forming unit per gram of tissue (cfu/g) and the same definition was employed for fecal samples. Each animal was genotyped with the Illumina BovineSNP50 BeadChip and after quality assurance filtering, 218 animals and 45,683 SNPs remained. We sought to identify loci associated with four different case/control classifications: presence of Map in the tissue, presence of Map in feces, presence of Map in both tissue and feces and presence of Map in tissue but not feces. A case-control genome wide association study (GWA) was conducted to test the four different classifications of Map infection status (Cases) when compared to a Map negative control group (Control). Regions on chromosomes 1, 5, 7, 8, 16, 21 and 23 were identified that showed a moderate significance (P less than 5x10E-5). Regions on chromosomes 3 and 9 were identified with a high level of association to the presence of Map in tissue and both tissue and feces, respectively (P less than 5x10E-7, genome-wide Bonferonni P less than 0.05).