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.

Olanrewaju B. Morenikeji,Olusola Ojurongbe,Bolaji N. Thomas,Anna L. Capria

doi:10.3390/genes11010112

Olanrewaju B. Morenikeji, Olusola Ojurongbe + Show 2 more

Open Access

https://doi.org/10.3390/genes11010112

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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.

Highlights

In recent years, the increasing availability of extensive sequencing data for livestock species due to the reduction in genome sequencing cost has provided an opportunity for comprehensive elucidation of genetic diversity and selection sweeps among and between species [1,2]
Some studies have shown that bovine disease tolerance comprises a better capacity to control parasitemia and limit anemia development [8,9], which we postulate to be the opposite in susceptible cattle breeds
In order to identify the functions and examine the possible variations in the biological process regulated by cluster differentiation antigen 14 (CD14) promoter micro RNAs (miRNAs) between the two breeds, we identified miRNAs and their functions using mirPath v

Summary

Introduction

The increasing availability of extensive sequencing data for livestock species due to the reduction in genome sequencing cost has provided an opportunity for comprehensive elucidation of genetic diversity and selection sweeps among and between species [1,2]. Cattle breeds with differing genetic diversities have evolved due to different environmental pressures, including heat stress, infectious diseases, and harsh climate, to the end, developing unique gene variants or footprints of adaptation allowing them to cope with environmental or disease challenges [4,5,6]. Some studies have shown that bovine disease tolerance comprises a better capacity to control parasitemia and limit anemia development [8,9], which we postulate to be the opposite in susceptible cattle breeds. A proper innate immune response is imperative to overcome a pathogenic challenge or confer disease tolerance. Variants of the genes mediating innate immune pathway may play a crucial role in tolerance or susceptibility to disease.

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