- Genome-wide association study of Mycobacterium avium subspecies Paratuberculosis infection in Chinese Holstein. - Background: Paratuberculosis is a contagious, chronic and enteric disease in ruminants, which is caused by Mycobacterium avium subspecies paratuberculosis ( MAP ) infection, resulting in enormous economic losses worldwide. - understanding of the mechanisms of paratuberculosis and benefit animal genetic improvement. - 1 Key Laboratory of Animal Genetics and Breeding of Ministry of Agriculture, National Engineering Laboratory of Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China Full list of author information is available at the end of the article. - 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0. - Symptoms of the disease include diar- rhea and weight loss that eventually leads to death. - Once a cow shows symptoms of JD, there is no treatment so the only effective means to get rid of the disease is to cull.. - Changes in herd management could help to reduce JD, but understanding resistance in cattle will allow for better management of the disease. - Exploring the genetic variants that con- tribute to host susceptibility to infection by MAP is im- portant both for animal genetic improvement programs and for a better understanding of the underlying mecha- nisms of disease.. - Zare et al. - We collected a 500 μL blood sample from the caudal vein of each cow and performed a regular quar- antine inspection of the farms during September 2014.. - The MAP status of an animal was expressed as a percentage of the sample to positive ratio (S/P) with the formula: S/P ratio = [(optical density (OD) of the sample – OD of the negative control. - (OD of positive sample – OD of the negative control. - Out of the 8214 detected cows, 185 positive individuals (case) and 760 negative individuals (control) from 6 herds were used for GWAS. - The DNA of the remaining 412 cows in the second sub-group were extracted from hair by GeneSeek with QIAamp® DNA Mini Kit (QIAGEN Inc., Valencia, CA, USA) and then genotyped with the Gene- Seek Genomic Profiler HD v2 (138,893 SNPs, GeneSeek, Lincoln, NE, USA). - After imput- ation, we compared the imputed and masked actual ge- notypes of the selected 100 cows to calculate the percentage of genotypes that are consistent between them.. - coefficient of the observed statistic on the expected stat- istic. - α is a vector of the corresponding coefficients including the intercept. - β is the effect size of the marker. - Here T 2 k ¼ β ^ 2 k = varð β b k Þ, where β b k is the ef- fect of the k th SNP. - σ ^ 2 Ψ ^ is an esti- mate of the null variance/covariance matrix of Y . - Consider- ing the features of the RM test and the data structure of this study being based on a corrected pedigree, we adopted the RM test for association analysis. - Following the suggestion of the Welcome Trust Case Control Consortium [48], two P value thresholds of and were considered as genome-wide. - Using BioMart in the Ensembl database (Ensembl Genes 92), genes within 1 Mb of the significant SNPs were re- trieved based on the UMD 3.1 assembly. - In addition, we compared the regions within 1 Mb of the significant SNPs with the reported cattle to QTLs for JD tolerance and MAP susceptibility in the Animal QTL database (http://www.animalgenome.org/cgi-bin/. - Minus log10 of the P value is indicated on the y-axis and map location of the SNP is indicated on the x-axis. - GO and Pathway analysis were performed by KOBAS 3.0 to determine the biological functions of the 343 genes. - 0.05) such as autoimmune thyroid disease and enrichment of the interleukin signaling path- way (Additional file 9: Table S4). - After comparing these QTLs with the regions within 1 Mb of the 26 significant SNPs, 2 QTLs identi- fied before [30, 37] located in BTA23. - It is common that the discrepancy caused by this reason, such as the report of Alpay et al.. - [36] and Sallam et al. - Among the 26 significant SNPs detected by two methods, BovineHD Mb) located on BTA7 in this study was close to SNPs detected by Pant et al. - Therefore, these three genes might play important roles in the pathogen- esis of the disease [27]. - SNP BovineHD4100015938 on BTA23 (8.98 Mb) was close to ARS-BFGL-NGS Mb) and ARS-BFGL-NGS Mb) reported by Zare et al. - SNP Bovi- neHD Mb) located on BTA23 was very close to ARS-BFGL-NGS Mb) reported by Zare et al. - in Jersey cattle [35], and close to ss Mb) reported by Minozzi et al. - Leite et al. - Comb- ing this information with related genes found above, the 32 ~ 33 Mb region of BTA23 may be a case of a genomic region associated with MAP infection, which corresponds to the report of Zare et al. - MAP: Mycobacterium avium subspecies Paratuberculosis. - Funding bod- ies did not have a role in the design of the study and collection, analysis, and interpretation of data, neither in writing the manuscript.. - All protocols for collection of the blood and hair samples of China Holstein cows were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at China Agricultural University. - Blood and hair samples were collected specifically for this study following standard procedures with the full agreement of the Beijing Dairy Cattle Center who owned the animals.. - Koets AP, Adugna G, Janss LL, van Weering HJ, Kalis CH, Wentink GH, et al.. - Genetic variation of susceptibility to Mycobacterium avium ssp.. - 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