Genome-wide association study of Mycobacterium avium subspecies Paratuberculosis infection in Chinese Holstein

Abstract

BackgroundParatuberculosis 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. There is currently no effective cure for MAP infection or a vaccine, it is thus important to explore the genetic variants that contribute to host susceptibility to infection by MAP, which may provide a better understanding of the mechanisms of paratuberculosis and benefit animal genetic improvement. Herein we performed a genome-wide association study (GWAS) to identify genomic regions and candidate genes associated with susceptibility to MAP infection in dairy cattle.ResultsUsing Illumina Bovine 50 K (54,609 SNPs) and GeneSeek HD (138,893 SNPs) chips, two analytical approaches were performed, GRAMMAR-GC and ROADTRIPS in 937 Chinese Holstein cows, among which individuals genotyped by the 50 K chip were imputed to HD SNPs with Beagle software. Consequently, 15 and 11 significant SNPs (P < 5 × 10− 5) were identified with GRAMMAR-GC and ROADTDRIPS, respectively. A total of 10 functional genes were in proximity to (i.e., within 1 Mb) these SNPs, including IL4, IL5, IL13, IRF1, MyD88, PACSIN1, DEF6, TDP2, ZAP70 and CSF2. Functional enrichment analysis showed that these genes were involved in immune related pathways, such as interleukin, T cell receptor signaling pathways and inflammatory bowel disease (IBD), implying their potential associations with susceptibility to MAP infection. In addition, by examining the publicly available cattle QTLdb, a previous QTL for MAP was found to be overlapped with one of regions detected currently at 32.5 Mb on BTA23, where the TDP2 gene was anchored.ConclusionsIn conclusion, we identified 26 SNPs located on 15 chromosomes in the Chinese Holstein population using two GWAS strategies with high density SNPs. Integrated analysis of GWAS, biological functions and the reported QTL information helps to detect positional candidate genes and the identification of regions associated with susceptibility to MAP traits in dairy cattle.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5385-3) contains supplementary material, which is available to authorized users.

Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression

“…Using linear regression analysis, we identified 192 and 48 cis-eQTLs associated with the expression of 145 and 43 genes in PB and ICV, respectively. Only one of the identified cis-eQTLs, the rs109604269 (P FDR = 0.011), was previously found to be associated with susceptibility to MAP infection 36 . Although the number of individual samples in this first part of the study was limited (N = 28), three of the identified cis-eQTLs were associated with PTB susceptibility in a larger cattle population (N = 986).…”

Identification of the ABCC4, IER3, and CBFA2T2 candidate genes for resistance to paratuberculosis from sequence-based GWAS in Holstein and Normande dairy cattle

“…Individual diagnostic tests for paratuberculosis are known to lack sensitivity and specificity, and these characteristics have been put forward as explanations for the low heritability of MAP-related traits that has been reported in the literature. Since the study of Settles et al in 2009 [9] to the most recent publication in 2019, 13 GWAS analyses have been conducted for traits linked with bovine paratuberculosis [6][7][8][9][10][11][12][13][14][15][16][17][18]. These studies examined various numbers of animals and SNPs, and all succeeded in identifying genomic regions associated with MAP resistance/susceptibility.…”

“…As recently reviewed by Brito et al [6], various studies have shown the role of host genetics in resistance to MAP and have estimated heritability values for this trait between 0.03 and 0.27. In addition, numerous genomewide association studies (GWAS) have been conducted using genotyping of single-nucleotide polymorphisms (SNPs) at low [7], medium [8][9][10][11][12][13][14], or high [6,15,16] densities as well as whole-genome sequences [17,18] imputed from data of the 1000 Bull Genomes project [19]. These GWAS analyses have led to the identification of quantitative trait loci (QTL) associated with resistance/susceptibility to MAP on all Bos taurus (BTA) autosomes, with the most frequently identified QTL located on BTA1, 6, 7, and 23.…”

Host Genetics Underlying Pathological Outcomes to Mycobacterium Avium Subsp. Paratuberculosis Infection is Governed by Distinct Genetic Variants

“…NPAS2 is a core component of the circadian clock, an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function.The GWAS de ned 92 SNPS and 9 QTLs with a high association with the diffuse lesions and located in 6 chromosomes (BTA1, BTA3, BTA7, BTA8, BTA13 and BTA23) (Table3). By examining the available cattle QTL database, we observed that a QTL located on BTA7 (23.79-25.08 Mb) overlapped with a QTL previously associated with MAP susceptibility (QTL:166688)[20]. In addition, the QTL on BTA3 (63.43-64.43 Mb) overlapped with the QTL:167791 and QTL:2489 associated with bTb susceptibility and clinical mastitis, respectively[21][22].…”