Dataset Information

Genome-wide association studies reveal susceptibility loci for noninfectious claw lesions in Holstein dairy cattle

ABSTRACT: Sole ulcers (SU) and white line disease (WLD) are noninfectious claw lesions that arise due to compromised horn production and are common causes of lameness in dairy cattle, imposing welfare and profitability concerns. The low to moderate heritability estimates of SU and WLD susceptibility indicate that genetic selection could reduce their prevalence. To identify loci associated with SU and WLD susceptibility, generalized linear mixed model (GLMM) regression and random forest (RF) genome-wide association studies (GWAS) were performed. Cows from five commercial dairies in California were classified as sound controls having no instances of lameness and above six years of age (n = 102) or cases having SU (n = 152), WLD (n = 117), SU and/or WLD (SU+WLD, n = 198), or any type of noninfectious claw lesion (n = 217). Top SNPs were defined as those passing Bonferroni-corrected suggestive and significance thresholds in the GLMM analysis or those that a validated RF model considered important. Effects of top SNPs were quantified using Bayesian estimation. Linkage disequilibrium (LD) blocks defined by top SNPs were explored for candidate genes and previously identified, functionally relevant quantitative trait loci. The GLMM GWAS revealed regions of association on BTA8 for SU and BTA13 common to WLD, SU+WLD, and noninfectious claw lesions. Bayesian estimation of effect sizes indicated that these SNPs had effects significantly different from zero, indicating their small but notable contribution to susceptibility. Promising candidate genes identified in these regions were involved in wound healing, skin lesions, bone growth and mineralization, adipose tissue, and keratinization. The LD block defined by the most significant SNP on BTA8 for SU included a SNP previously reported to be associated with SU. The RF models were overfitted, indicating that SNP effects were very small and thereby preventing meaningful interpretation of SNPs with the highest importance values and downstream analyses. These findings suggested that variants associated with a variety of physiological systems may contribute to susceptibility for noninfectious claw lesions, demonstrating the complexity of genetic predisposition.

ORGANISM(S): Bos taurus

PROVIDER: GSE165945 | GEO | 2021/07/23

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:The Systemic Capillary Leak Syndrome (SCLS) is an extremely rare, orphan disease that resembles systemic anaphylaxis. The disorder is characterized by repeated, transient, and seemingly unprovoked episodes of hypotensive shock and peripheral edema due to transient endothelial hyperpermeability. SCLS is often accompanied by a monoclonal gammopathy of unknown significance (MGUS). Using Affymetrix Single Nucleotide Polymorphism (SNP) microarrays, we performed the first genome-wide SNP analysis of SCLS in a cohort of 12 disease subjects and 18 controls. Exome capture sequencing was performed on genomic DNA from nine of these patients as validation for the SNP-chip discoveries and de novo data generation. We identified candidate susceptibility loci for SCLS, which included a region flanking CAV3 (3p25.3) as well as SNP clusters in PON1 (7q21.3), PSORS1C1 (6p21.3), and CHCHD3 (7q33). Among the most highly ranked discoveries were gene-associated SNPs in the uncharacterized LOC100130480 gene (rs6417039, rs2004296). Top case-associated SNPs were observed in BTRC (rs1235580, 3rs4436485), ARHGEF18 (rs11668246), CDH13 (rs4782779), and EDG2 (rs12552348), which encode proteins with known or suspected roles in B cell function and/or vascular integrity. SNPs that were significantly associated with SCLS by microarray analysis were also detected and validated by exome deep sequencing. Functional annotation of highly ranked SNPs revealed enrichment of cell projections, cell junctions and adhesion, and molecules containing pleckstrin homology, Ras/Rho regulatory, and immunoglobulin Ig-like C2/fibronectin type III domains, all of which involve mechanistic functions that correlate with the SCLS phenotype. These results highlight SNPs with potential relevance to SCLS. Our study cohort included 12 patients with SCLS. The control group included 17 age, sex and ethnicity-matched healthy donors (including two relatives of SCLS patients), and a reference sample supplied by the SNP-chip manufacturer (Affymetrix), for which age information was not available. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from purified B lymphocytes.

Dataset Information

Genome-wide association studies reveal susceptibility loci for noninfectious claw lesions in Holstein dairy cattle

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure