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Title: WHOLE GENOME-WIDE SNP ASSOCIATION: IDENTIFICATION OF SUSCEPTIBILITY ALLELES FOR PARASITIC INFECTION

Author
item Van Tassell, Curtis - Curt
item Sonstegard, Tad
item MATUKUMALLI, LAKSHMI - George Mason University
item Schroeder, Steven - Steve
item Kim, Eui-Soo
item Gasbarre, Louis

Submitted to: BARC Poster Day
Publication Type: Abstract Only
Publication Acceptance Date: 4/1/2009
Publication Date: 4/15/2009
Citation: Silva, M.V., Van Tassell, C.P., Sonstegard, T.S., Matukumalli, L.K., Schroeder, S.G., Kim, E., Gasbarre, L.C. 2009. WHOLE GENOME-WIDE SNP ASSOCIATION: IDENTIFICATION OF SUSCEPTIBILITY ALLELES FOR PARASITIC INFECTION. BARC Poster Day.

Interpretive Summary:

Technical Abstract: QTL for parasite indicator traits in cattle are ideal targets for study of marker assisted selection; however the phenotypic data and available resource populations were not optimal for reliable QTL identification. Fecal egg count (FEC) values, which are used to measure resistance to nematodes, are not “normally” distributed and logarithmic transformations fail to properly normalize this data in most cases. FEC data recorded for 410 animals between 1992 and 2003 from the BARC Angus herd were transformed using an extension of the Box-Cox transformation to approach normality. DNA for genetic analysis has been acquired for all animals from the resource population and over 70 sires in the historic pedigree, in total of 611 animals. Genotyping was performed using Illumina’s BovineSNP50 chip. For GWAS, SNP with a call rate (<98%), departure from Hardy-Weinberg equilibrium (exact test p<0.01), and minor allele frequency below 5 percent were excluded from the final analysis (26,158 markers retained). All the statistical analyses were carried out with scripts in the R environment and Fortran. Empirical p-values were corrected for genome-wide testing and maximization across genetic models, and a genome-wide significance level of 0.05 (two-sided) and Bonferroni corrected level of 0.01 were used. The five most significant SNP were found on Chr 6 and are localized within a single linkage disequilibrium (LD) block at the same region of ubiquitin-conjugating enzyme E2K gene, which has a critical role in the function of the adaptive immune system. These findings provide the first evidence of biomarkers that contribute to early disease detection and primary prevention strategies for parasite infection in cattle and suggest new molecular targets for disease-modifying therapies (secondary prevention). Correlation studies of genotypes to prognostic outcomes may predict the effect of treatments targeting these genes and their proteins; thus, reducing costs to identify animals most likely to benefit from treatment ("personalized therapy"). Supported by USDA ARS CRIS Project No. 1265-31000-098-00D