The Use of Kosher Phenotyping for Mapping QTL Affecting Susceptibility to Bovine Respiratory Disease

<div><p>Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in feedlot cattle, caused by multiple pathogens that become more virulent in response to stress. As clinical signs often go undetected and various preventive strategies failed, identification of genes affecting BRD is essential for selection for resistance. Selective DNA pooling (SDP) was applied in a genome wide association study (GWAS) to map BRD QTLs in Israeli Holstein male calves. Kosher scoring of lung adhesions was used to allocate 122 and 62 animals to High (Glatt Kosher) and Low (Non-Kosher) resistant groups, respectively. Genotyping was performed using the Illumina BovineHD BeadChip according to the Infinium protocol. Moving average of -logP was used to map QTLs and Log drop was used to define their boundaries (QTLRs). The combined procedure was efficient for high resolution mapping. Nineteen QTLRs distributed over 13 autosomes were found, some overlapping previous studies. The QTLRs contain polymorphic functional and expression candidate genes to affect kosher status, with putative immunological and wound healing activities. Kosher phenotyping was shown to be a reliable means to map QTLs affecting BRD morbidity.</p></div

A cluster of significant -LogP values on BTA 29 at about 30 Mb (red arrow; Fig 2 and Table 2).

<p>Blue diamonds, -LogP values of the markers; Avg 100K, moving average -LogP values of windows of 23 markers (≈ 100Kb; see text). Note that for this cluster the peak value of the moving average exceeds the -LogP = 2.0 threshold chosen to declare significance.</p

Number of individuals in the pools.

<p>Number of individuals in the pools.</p

Effects of QTLR’s genes and pathogens.

<p>Effects of QTLR’s genes and pathogens.</p

Example of a region with two mapped QTLRs that are possibly only one putative QTLR.

<p>QTLRs 5 and 6 on BTA 2. Red and black vertical bars on the X-axis, QTLRs 5 and 6 marker locations; Blue diamonds, -LogP values of the markers; Yellow squares (QTLR 5) and green diamonds (QTLR 6): X-axis, mean location of the markers in the window; Y-axis, mean -LogP of the window; red arrow, inter QTLR cluster. Three uppermost horizontal bars from top down: significance thresholds for individual markers at PFP = 0.05, 0.10 and 0.20, respectively.</p

Tizioto <i>et al</i>. [27] differentially expressed genes found in the QTLRs of the present study.

<p>Tizioto <i>et al</i>. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153423#pone.0153423.ref027" target="_blank">27</a>] differentially expressed genes found in the QTLRs of the present study.</p

Examples of chromosomal regions with one QTLR but possibly including two putative QTLRs.

<p>a. QTLR 3 on BTA 1. b. QTLR 4 on BTA 2. c. QTLR 14 on BTA 16. Vertical bars on the X-axis, QTLR markers locations; Blue diamonds, -LogP values of the markers; Yellow squares: X-axis, mean location of the markers in the window; Y-axis, mean -LogP of the window. Three uppermost horizontal bars from top down: significance thresholds for individual markers at PFP = 0.05, 0.10 and 0.20, respectively.</p

Complete list of all genes within the QTLRs or within 0.5 Mb upstream or downstream of the QTLR boundaries.

<p>Complete list of all genes within the QTLRs or within 0.5 Mb upstream or downstream of the QTLR boundaries.</p

Critical P-values and number of significant SNPs, by PFP level.

<p>Critical P-values and number of significant SNPs, by PFP level.</p

Weighted average of variances (Var(pB) of marker frequencies among replicates within GK and NK tails, pooled across all markers within bins.

<p>Weighted average of variances (Var(pB) of marker frequencies among replicates within GK and NK tails, pooled across all markers within bins.</p