SNP Diversity in CD14 Gene Promoter Suggests Adaptation Footprints in Trypanosome Tolerant N’Dama (Bos taurus) but not in Susceptible White Fulani (Bos indicus) Cattle

Abstract

Immune response to infections has been shown to be mediated by genetic diversity in pattern recognition receptors, leading to disease tolerance or susceptibility. We elucidated naturally occurring variations within the bovine CD14 gene promoter in trypanosome-tolerant (N’Dama) and susceptible (White Fulani) cattle, with genomic and computational approaches. Blood samples were collected from White Fulani and N’Dama cattle, genomic DNA extracted and the entire promoter region of the CD14 gene amplified by PCR. We sequenced this region and performed in silico computation to identify SNP variants, transcription factor binding sites, as well as micro RNAs in the region. CD14 promoter sequences were compared with the reference bovine genome from the Ensembl database to identify various SNPs. Furthermore, we validated three selected N’Dama specific SNPs using custom Taqman SNP genotyping assay for genetic diversity. In all, we identified a total of 54 and 41 SNPs at the CD14 promoter for N’Dama and White Fulani respectively, including 13 unique SNPs present in N’Dama only. The significantly higher SNP density at the CD14 gene promoter region in N’Dama may be responsible for disease tolerance, possibly an evolutionary adaptation. Our genotype analysis of the three loci selected for validation show that mutant alleles (A/A, C/C, and A/A) were adaptation profiles within disease tolerant N’Dama. A similar observation was made for our haplotype analysis revealing that haplotypes H1 (ACA) and H2 (ACG) were significant combinations within the population. The SNP effect prediction revealed 101 and 89 new transcription factor binding sites in N’Dama and White Fulani, respectively. We conclude that disease tolerant N’Dama possessing higher SNP density at the CD14 gene promoter and the preponderance of mutant alleles potentially confirms the significance of this promoter in immune response, which is lacking in susceptible White Fulani. We, therefore, recommend further in vitro and in vivo study of this observation in infected animals, as the next step for understanding genetic diversity relating to varying disease phenotypes in both breeds.

Integrative Network Analysis of Predicted miRNA-Targets Regulating Expression of Immune Response Genes in Bovine Coronavirus Infection

“…The GERP scores were negative, indicating that substitutions occur at a rate that is greater than neutral, suggesting that substitutions are tolerated in these locations, and it is likely that they are not detrimental. The variants may even be beneficial, as previously described in which similar variation in mature miRNAs targeted CD14 gene, thus regulating its expression during bovine trypanosomosis (Morenikeji et al, 2020). Further work is needed to validate these predictions with in vitro analyses examining miRNA expression, binding, and their effect on the host immune response to bovine coronaviruses.…”

Characterization and Expression Analysis ofNitrate Reductase 6-1ABDGene in Hexaploid Bread Wheat Under Different Nitrogen Regime

“…Probably this phenomena of higher transversions is NR 6-1 specific, which has led to more number of amino acid changes, though they were tolerated in the functional domains of the enzyme and functionality was retained. However, such a higher rate of transversion in the gene does exist, e.g, CD14 gene in Bos taurus and Bos indicus (Morenikeji et al 2020); MYB gene in chickpea (Roorkiwal et al 2014) etc.…”

Molecular genotyping reveals mixed bovine and human trypanosomiasis in cattle from West Africa

“…[3]. The previous studies [4][5][6][7] have shown that certain cattle breeds, such as N'Dama are trypanotolerant with the ability to control parasitemia and anemia, thus harboring the parasite and serving as reservoir hosts. This is thought to be an evolutionary adaptation that the N'Dama breed acquired, upon exposure to trypanosomiasis after being introduced to sub-Saharan Africa.…”