Cattle genome-wide analysis reveals genetic signatures in trypanotolerant N'Dama.

Indigenous cattle in Africa have adapted to various local environments to acquire superior phenotypes that enhance their survival under harsh conditions. While many studies investigated the adaptation of overall African cattle, genetic characteristics of each breed have been poorly studied. We performed the comparative genome-wide analysis to assess evidence for subspeciation within species at the genetic level in trypanotolerant N'Dama cattle. We analysed genetic variation patterns in N'Dama from the genomes of 101 cattle breeds including 48 samples of five indigenous African cattle breeds and 53 samples of various commercial breeds. Analysis of SNP variances between cattle breeds using wMI, XP-CLR, and XP-EHH detected genes containing N'Dama-specific genetic variants and their potential associations. Functional annotation analysis revealed that these genes are associated with ossification, neurological and immune system. Particularly, the genes involved in bone formation indicate that local adaptation of N'Dama may engage in skeletal growth as well as immune systems. Our results imply that N'Dama might have acquired distinct genotypes associated with growth and regulation of regional diseases including trypanosomiasis. Moreover, this study offers significant insights into identifying genetic signatures for natural and artificial selection of diverse African cattle breeds.

Kim SJ ，Ka S ，Ha JW ，Kim J ，Yoo D ，Kim K ，Lee HK ，Lim D ，Cho S ，Hanotte O ，Mwai OA ，Dessie T ，Kemp S ，Oh SJ ，Kim H ... -  《BMC GENOMICS》

Immunogenetic influences on tick resistance in African cattle with particular reference to trypanotolerant N'Dama (Bos taurus) and trypanosusceptible Gobra zebu (Bos indicus) cattle.

In sub-Saharan Africa, tick infestation and tick-borne infections together with tsetse-transmitted trypanosomosis arguably constitute the main parasitological disease complex constraining livestock production. Resistance to tick attack and tick-borne micro-organisms (TBMs) varies among different breeds of cattle. The magnitude of losses due to these parasites is related to an extent to the degree of breed resistance. Generally, zebu (Bos indicus) cattle possess a higher resistance to ticks and TBMs than European (Bos taurus) cattle. The host's immune system would appear to be the single most important factor that regulates this resistance. This paper reports on the main effector immune mechanisms governing resistance against ticks and TBMs. The cellular immune response appears more effective and stable than humoral immunity in modulating resistance to ticks and TBMs. Similarities between the immune mechanisms employed by trypanotolerant N'Dama (B. taurus) cattle, when infected with trypanosomes, and those elicited by tick bites and TBMs seem to exist, particularly at the skin level in the early phases of parasitic invasion. Moreover, there is evidence that in the N'Dama breed, resistance against ticks per se also has a genetic basis. Therefore, the N'Dama appears to be a unique breed in that it exhibits resistance to several parasitic diseases and/or infections, including helminths, when compared to other cattle breeds in West Africa. It is concluded that the multi-parasite resistant traits of the N'Dama breed should be exploited in those areas where trypanosomosis, ticks and tick-borne diseases constrain animal production. This should be of benefit for low-input farming systems where the use of chemicals for prophylaxis and therapy is limited by their relatively high cost. Additionally, the potential contribution of multiple disease resistant N'Dama cattle should be considered in crossbreeding programmes with exotic dairy breeds for increasing milk production in West Africa.

Mattioli RC ，Pandey VS ，Murray M ，Fitzpatrick JL ... -  《ACTA TROPICA》

Exploring evidence of positive selection signatures in cattle breeds selected for different traits.

Since domestication, the genome landscape of cattle has been changing due to natural and artificial selection forces resulting in several general and specialized cattle breeds of the world. Identifying genomic regions affected due to these forces in livestock gives an insight into the history of selection for economically important traits and genetic adaptation to specific environments of the populations under consideration. This study explores the genes/genomic regions under selection in relation to the phenotypes of Holstein, Hanwoo, and N'Dama cattle breeds using Tajima's D, XP-CLR, and XP-EHH population statistical methods. The whole genomes of 10 Holstein (South Korea), 11 Hanwoo (South Korea), and 10 N'Dama (West Africa-Guinea) cattle breeds re-sequenced to ~11x coverage and retained 37 million SNPs were used for the study. Selection signature analysis revealed 441, 512, and 461 genes under selection from Holstein, Hanwoo, and N'Dama cattle breeds, respectively. Among all these, seven genes including ARFGAP3, SNORA70, and other RNA genes were common between the breeds. From each of the gene lists, significant functional annotation cluster terms including milk protein and thyroid hormone signaling pathway (Holstein), histone acetyltransferase activity (Hanwoo), and renin secretion (N'Dama) were enriched. Genes that are related to the phenotypes of the respective breeds were also identified. Moreover, significant breed-specific missense variants were identified in CSN3, PAPPA2 (Holstein), C1orf116 (Hanwoo), and COMMD1 (N'Dama) genes. The genes identified from this study provide an insight into the biological mechanisms and pathways that are important in cattle breeds selected for different traits of economic significance.

Taye M ，Lee W ，Jeon S ，Yoon J ，Dessie T ，Hanotte O ，Mwai OA ，Kemp S ，Cho S ，Oh SJ ，Lee HK ，Kim H ... -  《-》

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.

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 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 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. 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 promoter for N'Dama and White Fulani respectively, including 13 unique SNPs present in N'Dama only. The significantly higher SNP density at the 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 ( and ) were adaptation profiles within disease tolerant N'Dama. A similar observation was made for our haplotype analysis revealing that haplotypes H1 () and H2 () 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 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.

Morenikeji OB ，Capria AL ，Ojurongbe O ，Thomas BN ... -  《Genes》

Divergent antimicrobial peptide (AMP) and acute phase protein (APP) responses to Trypanosoma congolense infection in trypanotolerant and trypanosusceptible cattle.

African animal trypanosomiasis (AAT) is endemic across Sub-Saharan African and is a major constraint to livestock production. The ability of certain cattle breeds to remain productive despite infection is known as trypanotolerance; however, the underlying immune mechanisms contributing to this trait remain poorly understood. Antimicrobial peptides (AMPs) and acute phase proteins (APPs) are evolutionarily conserved effector molecules of the innate immune system that have important roles in the resolution of infection and activation of the adaptive immune response. Expression levels of AMP genes (TAP, LAP, BNBD4, DEFB1, DEFB5 and LEAP2) and APP genes (HP, CP, AGP, LBP, SAA3 and CRP) were investigated using real time quantitative reverse transcription PCR (qRT-PCR) in peripheral blood mononuclear cells (PBMC) isolated from two breeds of African cattle (trypanotolerant N'Dama and trypanosusceptible Boran), experimentally infected with Trypanosoma congolense. Haptoglobin and serum amyloid A (SAA) were also measured in plasma using quantitative protein assays. Results demonstrated that tracheal antimicrobial peptide (TAP) gene expression increased by 32-fold in Boran, compared to only 3-fold in N'Dama, by 14 days post-infection (dpi) and rising to 136-fold at 29 dpi in Boran, compared to 47-fold in N'Dama (P<0.05). Protein expression levels of SAA are elevated in N'Dama, rising to 163 microg/ml at 14 dpi compared with 72 microg/ml in Boran. The SAA expression profile mirrors the wave of parasitaemia detected in N'Dama. Seven single nucleotide polymorphisms (SNPs) were identified in the promoter regions of the SAA3 and SAA4 genes, which are predicted to affect transcription factor binding and thereby contributing to the differential patterns of expression detected between the breeds. Whereas elevated TAP expression is a conserved component of the innate immune response to infection in both breeds, higher SAA expression levels may contribute toward trypanotolerance in N'Dama.

Meade KG ，O'Gorman GM ，Hill EW ，Narciandi F ，Agaba M ，Kemp SJ ，O'Farrelly C ，MacHugh DE ... -  《-》