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New insights into resistance to paratuberculosis from sequence-based GWAS in Holstein cattle

Abstract : Bovine paratuberculosis is a contagious and incurable disease, caused by Mycobacterium avium subsp. paratuberculosis (MAP), with adverse effects on animal welfare and serious economic consequences. In a previous GWAS conducted on 1644 Holstein cows with an accurately defined status for MAP (controls, non-clinical and clinical cases) and whole genome sequences (WGS) imputed using the 6th Run of the 1000 bull genomes (1kBG) project (multibreed population, UMD3.1 reference genome), we identified three genomic regions on chromosomes 12, 13, and 23. The objective of the present study was to conduct further investigations using the 7th Run of the 1kBG, which includes a larger Holstein population with WGS based on the recent ARS-UCD1.2 reference genome. 50K genotypes of the 1644 Holstein cows were imputed to the high-density (HD) level with FImpute and then up to WGS with Minimac using reference sets of 776 and 700 Holstein bulls, respectively. GWAS was carried out with GCTA, testing the individual effect of ~25M variant and accounting for the population structure through a HD-based genomic relationship matrix. After filtering variants for low imputation accuracy (R² < 0.3) or frequency (MAF < 0.001), 4815 variants had significant effects (6 ≤ -log(P) ≤ 34.5) on resistance to MAP. They were located in eight different genomic regions on chromosomes 6, 9, 12, 13 (2 regions), 14, 18, and 23. Two-thirds of these variants (3194) were located in genes, mainly in introns (2170), upstream or downstream regions (907), and exons (101 including 65 non-synonymous). In each region, the variants with the most significant effects were located in the TMPRSS11F, HS6T3, ABCC4, SNTA1, SNTB1, NOTCH4, NFKBTL1, ATP6V1G2, DDX39B, and ELOVL5 genes. This study confirms the three genomic regions we detected before and reveals five novel regions for resistance to MAP.
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https://hal.inrae.fr/hal-03336111
Contributor : Didier Boichard <>
Submitted on : Monday, September 6, 2021 - 10:15:14 PM
Last modification on : Thursday, September 9, 2021 - 3:33:08 AM

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M.P. Sanchez, Raphaël Guatteo, Arnaud Delafosse, Aurore Davergne, Cécile Grohs, et al.. New insights into resistance to paratuberculosis from sequence-based GWAS in Holstein cattle. 72nd Annual Meeting EAAP, Aug 2021, Davos, Switzerland. ⟨hal-03336111⟩

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