Table 1. Genome sequence context for JMJD1C SNPs associated with bovine congestive heart failure (BCHF)

Authors: Heaton, Michael - Mike; Harhay, Gregory; Smith, Timothy - Tim; Kuhn, Kristen; KALBFLEISCH, THEODORE - University Of Kentucky; JOBMAN, ERIN - University Of Nebraska; VANDER LEY, BRIAN - University Of Nebraska

Submitted to: Figshare
Publication Type: Database / Dataset
Publication Acceptance Date: 5/17/2022
Publication Date: 5/17/2022
Citation: Heaton, M., Harhay, G., Smith, T.P.L., Kuhn, K., Kalbfleisch, T.S., Jobman, E., Vander Ley, B. 2022. Table 1. Genome sequence context for JMJD1C SNPs associated with bovine congestive heart failure (BCHF). Figshare. Dataset. https://doi.org/10.6084/m9.figshare.19780558.v1.
DOI: https://doi.org/10.6084/m9.figshare.19780558.v1

Interpretive Summary: Bovine congestive heart failure (BCHF) in feedlot cattle has become increasingly common in the Western Great Plains of North America at moderate elevations (3000 to 4500 ft). This disease is an untreatable, complex condition involving high blood pressure in the lungs, which leads to subsequent heart failure and death. BCHF is fundamentally distinct from the “brisket disease” observed in the high elevations of the Rocky Mountains (>7000 ft), since BCHF occurs at much lower elevations where animals with brisket disease were previously sent to recover. Individual feedlot operations have reported losses from BCHF exceeding $250,000 annually, which are comparable to losses from bovine respiratory disease at similar locations. Cattle herds affected with BCHF are typically bred and managed with the aim of achieving high-quality carcasses. Consequently, reducing the impact of BCHF is a priority for the beef industry. Previously, we have identified animals with end-stage heart failure from 30 different ranch sources and evaluated them together with their healthy pen mates. Genome-wide bead array genotyping technology was used to identify two major genes (ARRDC3 and NFIA) associated with BCHF. Here we used whole genome sequencing technology to identify a third major gene (JMJD1C) associated with BCHF. The newly discovered gene markers were not identified with the previous technology due to their absence on the BovineHD BeadChip array. Sequence and molecular details related to the new markers were made public to facilitate development of genetic tests needed for results validation and to provide early access for companies assisting producers with affected herds (doi: 10.6084/m9.figshare.19780558).

Technical Abstract: Background: The power and resolution of genome-wide association studies (GWAS) may be enhanced with increased DNA marker density and reduced ascertainment bias of whole genome sequence (WGS) technology compared to that of bead-based microarrays. However, validation of WGS marker associations may be challenging since preexisting assays for these variants will not always available. Here, our aim was to provide preliminary molecular, genetic, and statistical information for JMJD1C variants associated with bovine congestive heart failure (BCHF) for the purpose of assay development. Methods: A WGS data set with greater than 10-fold genome coverage per animal was generated from 102 BCHF matched case-control pairs.Paired nominal data from 11 million single nucleotide polymorphisms (SNPs), filtered for frequency and quality, were analyzed with McNemar’s test and sorted by false discovery rate (FDR). Results: A 45 kb region spanning introns 2 and 3 of JMJD1C on chromosome 28 was identified as being significantly associated with BCHF with a FDR q-value less than 0.05. This association was in addition to those in ARRDC3 and NFIA previously reported (Heaton et al. F1000Research 2022, 11:385). Nine linked SNPs in JMJD1C comprised exactly two haplotypes with an average minor allele frequency (MAF) of 0.005 and 0.132 in the cases and controls, respectively. Two copies of the major SNP alleles were associated with disease development, while one or two copies of the minor SNP alleles were not. There were 25 informative pairs for each of the nine linked SNPs, and the “protective” allele was absent from all 25 diseased animals in these informative pairs (McNemar’s b/c = 0/25, OR = 0, mid p-value = 3.0 x 10E-8, FDR = 9.8 x 10E-3). Conclusion: These preliminary results indicate that selection for the protective JMJD1C alleles may be useful in reducing BCHF in severely affected herds, however genotype assay development will be needed for further validation. The marker details are publicly available for use without restriction (https://doi.org/10.6084/m9.figshare.19780558.v1).