Wingless‐type MMTV integration site family member 2 (WNT2) gene is associated with resistance to MAP in faecal culture and antibody response in Holstein cattle. (23rd January 2015)

• Record Type: Journal Article
• Authors: Pauciullo, A.; Küpper, J.; Brandt, H.; Donat, K.; Iannuzzi, L.; Erhardt, G.
• Is Part Of: Animal genetics. Volume 46:Number 2(2015:Apr.)
• Page Start: 122
• Page End: 132
• Publication Date: 2015-01-23
• Subjects: Animal genetics -- Periodicals; 572.8
• DOI: 10.1111/age.12261
• Languages: English
• ISSNs: 0268-9146

Abstract

<abstract abstract-type="main" id="age12261-abs-0001"> <title>Summary</title> <p> <italic>Mycobacterium avium</italic> subspecies <italic>paratuberculosis</italic> (MAP) is a pathogenic bacterium responsible for the lethal Johne's disease in cattle. So far, several genome‐wide association studies (GWAS) have been carried out to identify chromosomal regions highly associated with Johne's disease. The aim of this study was to investigate the genetic variability within a pool of seven genes (<italic>LAMB1, DLD, WNT2, PRDM1, SOCS5, PTGER4</italic> and <italic>IL10</italic>) indicated by former GWAS/RNA‐Seq studies as putatively associated with MAP infections and to achieve a confirmation study of association with paratuberculosis susceptibility in a population of 324 German Holstein cattle (162 cases MAP positive and 162 controls MAP negative) using ELISA and fecal cultural tests. SNP validation and genotyping information are provided, quick methods for allelic discrimination were set up and transcription factor binding analyses were performed. The <italic>rs43390642:G>T</italic>SNP in the <italic>WNT2</italic> promoter region is associated with paratuberculosis susceptibility (<italic>P </italic>= 0.013), suggesting a protective role of the <italic>T</italic> allele (<italic>P </italic>=<italic> </italic>0.043; odds ratio 0.50 [0.25–0.97]). The linkage disequilibrium with the <italic>DLD rs134692583:A>T</italic> might suggest a combined mechanism of action of these neighboring genes in resistance to MAP infection, which is also supported by a significant effect shown by the haplotype <italic>DLD</italic><sup><italic>T</italic></sup><italic>/WNT2</italic><sup><italic>T</italic></sup> (<italic>P </italic>=<italic> </italic>0.047). <italic>In silico</italic> analysis predicted <italic>rs43390642:G>T</italic> and <italic>rs134692583:A>T</italic> as essential parts of binding sites for the transcription factors GR, C/EBP<italic>β</italic> and GATA‐1, hence suggesting a potential influence on <italic>WNT2</italic> and <italic>DLD</italic> gene expression. This study confirmed the region on BTA 4 (UMD 3.1: 50639460–51397892) as involved in tolerance/resistance to Johne's disease. In addition, this study clarifies the involvement of the investigated genes in MAP infection and contributes to the understanding of genetic variability involved in Johne's disease susceptibility.</p> </abstract>