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》

Whole genome characterization of autochthonous Bos taurus brachyceros and introduced Bos indicus indicus cattle breeds in Cameroon regarding their adaptive phenotypic traits and pathogen resistance.

African indigenous taurine cattle display unique adaptive traits shaped by husbandry management, regional climate and exposure to endemic pathogens. They are less productive with respect to milk and meat production which has been associated with amongst others, small size, traditional beliefs, husbandry practices, limited feed resources, disease burden and lack of sustained breeding for trait improvement. This resulted in the severe dwindling of their population size rendering them vulnerable to extinction. The Namchi taurine cattle breed is referred to as [Namchi (Doayo)] and shows resistance traits against trypanosome infection and exposure to tick infestation. Nonetheless, the historically later introduced Zebu cattle are the main cattle breeds in Africa today, even though they suffer more from locally prevailing pathogens. By using a whole genome sequencing approach, we sequenced with high depth for the first time the genomes of five cattle breeds from Cameroon in order to provide a valuable genetic resource for future African cattle breeding: the Namchi, an endangered trypano-tolerant taurine breed, the Kapsiki, an indigenous trypano-susceptible taurine breed, and three Zebu (Bos indicus indicus) breeds: Ngaoundere Gudali, White Fulani and Red Fulani. Approximately 167 Gigabases of raw sequencing data were generated for each breed and mapped to the cattle reference genomes ARS-UCD1.2 and UMD3.1.The coverage was 103 to 140-fold when aligning the reads to ARS-UCD1.2 with an average mapping rate of ~ 99%, and 22 to 30-fold when aligning the reads to UMD3.1 with an average mapping rate of ~ 64%. The single nucleotide polymorphisms (SNPs) obtained from analysis using the genome ARS-UCD1.2 were compared with reference genomes of European Bos taurus Holstein, the Asian Bos indicus Brahman, and the African trypanotolerant N'Dama breeds. A total of ~ 100 million (M) SNPs were identified and 7.7 M of those were breed-specific. An approximately 11.1 M constituted of small insertions and deletions. By using only breed-specific non-synonymous variants we identified genes as genetic signatures and associated Gene Ontology (GO) terms that could explain certain cattle-breed specific phenotypes such as increased tolerance against trypanosome parasites in the Namchi breed and heat tolerance in the Kapsiki breed. Phylogenetic analysis grouped, except for Namchi, the Bos taurus breeds Kapsiki, N'Dama and Holstein together while the B. indicus breeds White and Red Fulani, Gudali and Brahman clustered separately. The deviating result for Namchi indicates a hybrid status of the selected animal with a recent introgression of Zebu genes into its genome. The findings provide the first comprehensive set of genome-wide variant data of the most important Cameroonian cattle breeds. The genomic data shall constitute a foundation for breed amelioration whilst exploiting the heritable traits and support conservation efforts for the endangered local cattle breeds.

Paguem A ，Abanda B ，Achukwi MD ，Baskaran P ，Czemmel S ，Renz A ，Eisenbarth A ... -  《BMC GENETICS》

Potentials of single nucleotide polymorphisms and genetic diversity studies at HSP90AB1 gene in Nigerian White Fulani, Muturu, and N'Dama cattle breeds.

The study was aimed at genetic characterization of Nigerian breeds of Muturu, N'Dama, and White Fulani cattle breeds at heat shock protein 90AB1 locus. Also, the goal of the study was to detect the presence of single nucleotide polymorphisms (SNPs) at HSP90AB1 locus and consequently recommend them as bio-markers for thermo-tolerance potentials in Nigerian cattle breeds when exposed to assaults of thermal conditions/heat shock of tropical environment. Based on the previously published potentials of this candidate gene to lower assaults of thermal conditions/heat shock such as heat stress, the detected SNPs of HSP90AB1 within the population of the Nigerian cattle in this study will be recommended for population-based screening with a view to genetically improving those zebu cattle breeds that are more vulnerable to heat shock and assaults of thermal conditions. Total number of 200 blood samples were randomly collected from White Fulani (84 samples), Muturu (73 samples), and N'Dama (43 samples) breeds of cattle. Out of these, 20 DNA samples were randomly selected from each of the three cattle breeds and were used for DNA extraction and downstream analyses to further confirm findings of previous study, hence the goal of our study. DNA was extracted from the blood samples using the Zymo-bead DNA extraction kit and DNA sequencing of our samples was performed. A total number of 9 SNPs (within exons 5-6 coding regions) and 11 SNPs (within exons 12-13 coding regions) were detected at HSP90AB1 locus using the codon code aligner software. ARLEQUIN 2.0001 software was used to estimate the basic population genetic statistics while the DnaSP version 5.10.01 was used to estimate the genetic diversity indices. This study detected new SNPs (polymorphic sites) at HSP90AB1 locus within the DNAs of Nigerian White Fulani (WF), Muturu (MU), and N'Dama (ND) breeds of cattle. Within exons 5-6 coding regions, the N'Dama (ND) cattle breed had the highest for number of SNPs (5) and genetic diversity indices while White Fulani (WF) and Muturu (MU) had the least (2) number of SNPs each. Within exons 12-13 coding regions, WF had the highest numbers of SNPs (7) and genetic diversity indices while MU had the least number of SNPs (1) and genetic diversity indices. Some of the detected SNPs at HSP90AB1 locus were shared among the three breeds, suggesting that these three Nigerian cattle breeds showed shared ancestral alleles and lineage. Our study further revealed that HSP90AB1 is highly polymorphic/variable and diverse among the three Nigerian cattle breeds examined. Based on the previously documented thermo-tolerance potentials of members of HSP90 sub-family including the findings of our study, we hypothesize therefore that the presence of SNPs of HSP90AB1 within the DNAs of these three breeds of Nigerian cattle (WF, ND, and MU) may confer them thermo-tolerance potentials for thermal assault conditions and heat shock of the tropics at HSP90AB1 locus. Therefore, the detected SNPs can be recommended as bio-markers to improve the thermo-tolerance potentials of Nigerian breeds of zebu cattle raised under the challenges of heat shock for better adaptation and survival.

De Campos JS ，Onasanya GO ，Ubong A ，T Yusuff A ，Adenaike AS ，Mohammed AA ，Ikeobi CO ... -  《-》

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》

Trypanosome infections and tick infestations: susceptibility in N'Dama, Gobra zebu and Gobra x N'Dama crossbred cattle exposed to natural challenge and maintained under high and low surveillance of trypanosome infections.

Susceptibility to trypanosome infections and tick infestations was assessed in 51 N'Dama, 48 Gobra zebu and 37 Gobra x N'Dama crossbred (F1) cattle exposed to field-tick infestations and natural high tsetse challenge over more than one year. From these cattle, 12 animals of each breed were randomly selected and examined parasitologically for trypanosome infections and packed cell volume (PCV) twice a week (high surveillance, group HS). In the remaining 100 cattle trypanosome infection and PCV were monitored monthly (low surveillance, group LS). Mortality rates were recorded in both groups. Tick infestation was quantified fortnightly from all animals in group HS and from four to seven randomly selected animals of each breed in group LS. In both HS and LS groups, trypanocidal drug treatment was administered to trypanosome positive animals with PCV equal to or less than 20% or when they showed clinical evidence (dullness, weight loss) of trypanosomosis. In both groups, N'Dama cattle exhibited a superior capacity to control trypanosome infections and limit tick burdens. Particularly, in group HS N'Dama cattle showed lower trypanosome infection rate, higher mean PCV value, lower requirement for trypanocide treatments and lower tick load than crossbred and Gobra cattle in the corresponding group (P < 0.05 or greater). This was also true in N'Damas in comparison with crossbreds in group LS. Unfortunately, the high mortality occurring in Gobra cattle in group LS did not allow within group comparative analysis between N'Dama, Gobra and crossbred cattle overall the study period. No death occurred in N'Dama cattle maintained under high surveillance of trypanosome infection, while approximately 8% of crossbreds and 50% of Gobras died of trypanosomosis. In group LS, all Gobra and more than 70% of crossbred cattle died. In this group, mortality in N'Dama was limited to less than 16%. In both groups, differences in mortality were significantly higher (P < 0.01) in Gobras than in N'Damas. Within breed, animals of the three breeds maintained under high surveillance of trypanosomal infection showed higher mean PCV values, lower tick burdens and required proportionally less trypanocide treatments than corresponding cattle in group LS. The infection rate in N'Dama under high surveillance was lower in comparison with N'Dama cattle in group LS. There was no significant difference in mortality between groups within the N'Dama breed. Conversely, mortality rates were lower in crossbred and Gobra in group HS than in respective cattle in group LS. It was concluded that cattle of the three breeds suffered from trypanosomosis and that trypanosome infections affected tick susceptibility. However, N'Dama showed a superior ability to limit both the pathological effects of trypanosomosis and the level of tick infestations. Therefore, considering the cost of labour and consumable equipment required for a high surveillance, use of multi-disease resistant N'Dama cattle is recommended for the low-input traditional African farming systems in areas where trypanosomosis, ticks and tick-borne diseases are constraints to livestock production. Additional comparative investigations are needed to assess the impact of high surveillance scheme of trypanosome infection in different production systems in trypanotolerant and trypanosusceptible cattle exposed to different gradients of tsetse challenge.

Mattioli RC ，Jaitner J ，Clifford DJ ，Pandey VS ，Verhulst A ... -  《ACTA TROPICA》