|KISER, J - Washington State University|
|JOHNSON, K - Washington State University|
|HOFF, J - Washington State University|
|TAYLOR, J - University Of Missouri|
|NEIBERGS, H - Washington State University|
Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2016
Publication Date: 3/28/2017
Citation: Kiser, J.N., White, S.N., Johnson, K.A., Hoff, J., Taylor, J.F., Neibergs, H.L. 2017. Identification of loci associated with susceptibility to mycobacterium avium subspecies paratuberculosis (Map) tissue infection in cattle. Journal of Animal Science. 95:1080-1091.
Interpretive Summary: Johne’s disease is a contagious bacterial infection of the bovine small intestine caused by Mycobacterium avium ssp. paratuberculosis (Map). A previous genome wide association analysis in Holstein cattle identified two important gene regions with strong evidence for association and three others showing moderate association with Map tissue infection. The objectives of this study were to validate previous results in additional cattle populations including different breeds and areas of the U.S., as well as to identify new associated genetic loci. This study included Jersey dairy cattle, as well as Holstein cattle from the Pacific Northwest analyzed both individually and in combination with Holsteins from the Northeastern U.S. While this study did not validate any previously identified genetic loci, 22 new genetic loci were associated with Map tissue infection. Further, many candidate genes in these genetic regions may be related to bacterial entry and/or immune control of Map. These results add to knowledge of host genetics of Johne's disease susceptibility in cattle. In addition, these results contribute to the broader body of knowledge about susceptibility to mycobacterial pathogens, a group that includes pathogens responsible for tuberculosis in human populations. Once these genetic loci are validated in additional populations and refined to underlying functional mutations, they will contribute to selective breeding of cattle for reduced susceptibility to Johne's disease.
Technical Abstract: Johne’s disease is a contagious bacterial infection of cattle caused by Mycobacterium avium ssp. paratuberculosis (Map). A previous genome-wide association analysis (GWAA) in Holstein cattle identified QTL on BTA3 and BTA9 that were highly associated (P < 5 × 10-7) and on BTA1, BTA16, and BTA21 that were moderately associated (P < 5 × 10-5) with Map tissue infection. The objectives of this study were to validate previous GWAA results in Jersey cattle (n = 57), Holstein cattle from the Pacific Northwest (PNW, n = 205) and a combined Holstein population from the PNW and the Northeast (PNW + NE, n = 423), and also identify new loci associated with Map tissue infection. DNA was genotyped using the Illumina BovineSNP50 BeadChip, and the PNW + NE data was also imputed to whole genome sequence level using Run4 of the 1000 Bull Genomes project with Beagle v 4.1 and FImpute. Cases were ileocecal node positive and controls were negative for Map by quantitative PCR (qPCR). Individuals were removed for SNP call rate < 90%, and SNP were removed for genotype call rate < 90% or minor allele frequency < 1%. For the Jersey, PNW, and PNW + NE, GWAA were conducted using an allelic dosage model. For the PNW and the PNW + NE, an additional efficient mixed-model association eXpedited (EMMAX) analysis was performed using additive, dominance and recessive models. Seven QTL on BTA22 were identified in the Jersey population with the most significant (P = 4.45 × 10-6) located at 21.7 megabases (Mb). Six QTL were associated in the PNW and the PNW + NE analyses, including a QTL previously identified on BTA16 in the NE population. The most significant locus for the PNW was located on BTA21 at 61 Mb (P = 8.61 × 10-8) while the most significant locus for the PNW + NE was on BTA12 at 90 Mb (P = 2.33 × 10-5). No additional QTL were identified with the imputed GWAA. Putative positional candidate genes were identified within 50 kb 5’ and 3’ of each QTL. Two positional candidate genes were identified in Jersey cattle, 1 identified in the PNW and 8 in the PNW + NE populations. Many identified positional candidate genes are involved in signal transduction, have immunological functions, or have putative functional relevance in Map entry into host cells. This study supported 2 previously identified SNP within a QTL on BTA16 and identified 16 new QTL, including 2 found in the PNW and the PNW+NE, associated with Map tissue infection.