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Genome-wide association study and functional analyses of clinical and subclinical ketosis in Holstein cattle.

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Title: Genome-wide association study and functional analyses of clinical and subclinical ketosis in Holstein cattle.
Author: Soares, R.A.N.; Vargas, G.; Schenkel, F.S.; Squires, E.J.
Department: Department of Animal Biosciences
Abstract: Ketosis affects high yielding cows and it is one of the most frequent metabolic diseases in dairy cows causing high economic losses. Therefore,finding genetic markers for gene variants associated with resistance to ketosis is of interest to genetically select for less susceptible cows. The aim of this study was to identify and investigate genomic regions associated with clinical and subclinical ketosis in Holstein cattle. To achieve this, weighted single step genome-wide association study (wssGWAS)was performed considering 4 traits: clinical ketosis in first (CK1) and later lactations (from 2 to 5; CK2), and subclinical ketosis in first (SCK1) and later lactations (from 2 to 5; SCK2). The estimated breeding values (EBV) from 77,277 cows and 7,704 bulls were de-regressed and used as pseudo-phenotypes in the GWAS. The wssGWAS model was: y* = μ + Zaα + e, where y* is the vector of pseudo-phenotypes; μ is the overall mean; Za is a matrix that relates animals to pseudo-phenotypes; α is the vector of additive genetic effects and e is the vector of random residuals. The top-20 genomic regions explaining the largest proportion of the genetic variance were investigated for putative genes associated with the traits through functional analyses. Regions of interest were identified in chromosomes 2, 5 and 6 for CK1, 3, 6 and 7 for CK2, 1, 2 and 12 for SCK1 and 20, 11 and 25 for SCK2. The highest proportion of genetic variance explained by a region was located on BTA2 for SCK1. The highlighted genes potentially related to clinical and subclinical ketosis included ACAT2 and IFG1. Enrichment analyses of the candidate genes for the traits showed molecular functions and biological processes that are associated with fatty acid metabolism, synthesis and degradation of ketone bodies and inflammatory response. Several genomic regions and SNPs related to susceptibility to ketosis in dairy cattle, which were previously described in other studies were confirmed here. In addition, some novel potential regions were found that would warrant further investigation on their potential association with clinical and subclinical ketosis.
Description: Poster Presentation at the 2020 ADSA Annual Meeting (online).
URI: https://hdl.handle.net/10214/21211
Date: 2020-06
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Related Publications: R.A.N. Soares, et al. Genome-wide association study and functional analyses of clinical and subclinical ketosis in Holstein cattle. J. Dairy Sci. 103 (Suppl. 1). p. 167, M16, 2020.


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