Genetic diversity and population structure of Theileria parva in South Sudan.

Theileria parva is a parasitic protozoan that causes East Coast fever (ECF), an economically important disease of cattle in eastern, central and southern Africa. In South Sudan, ECF is considered a major constraint for livestock development in regions where the disease is endemic. To obtain insights into the dynamics of T. parva in South Sudan, population genetic analysis was performed. Out of the 751 samples included in this study, 178 blood samples were positive for T. parva by species-specific PCR, were collected from cattle from four regions in South Sudan (Bor = 62; Juba = 45; Kajo keji = 41 and Yei = 30) were genotyped using 14 microsatellite markers spanning the four chromosomes. The T. parva Muguga strain was included in the study as a reference. Linkage disequilibrium was evident when populations from the four regions were treated as a single entity, but, when populations were analyzed separately, linkage disequilibrium was observed in Bor, Juba and Kajo keji. Juba region had a higher multiplicity of infection than the other three regions. Principal components analysis revealed a degree of sub-structure between isolates from each region, suggesting that populations are partially distinct, with genetic exchange and gene flow being limited between parasites in the four geographically separated populations studied. Panmixia was observed within individual populations. Overall T. parva population genetic analyses of four populations in South Sudan exhibited a low level of genetic exchange between the populations, but a high level of genetic diversity within each population.

Co-infections determine patterns of mortality in a population exposed to parasite infection.

Many individual hosts are infected with multiple parasite species, and this may increase or decrease the pathogenicity of the infections. This phenomenon is termed heterologous reactivity and is potentially an important determinant of both patterns of morbidity and mortality and of the impact of disease control measures at the population level. Using infections with Theileria parva (a tick-borne protozoan, related to Plasmodium) in indigenous African cattle [where it causes East Coast fever (ECF)] as a model system, we obtain the first quantitative estimate of the effects of heterologous reactivity for any parasitic disease. In individual calves, concurrent co-infection with less pathogenic species of Theileria resulted in an 89% reduction in mortality associated with T. parva infection. Across our study population, this corresponds to a net reduction in mortality due to ECF of greater than 40%. Using a mathematical model, we demonstrate that this degree of heterologous protection provides a unifying explanation for apparently disparate epidemiological patterns: variable disease-induced mortality rates, age-mortality profiles, weak correlations between the incidence of infection and disease (known as endemic stability), and poor efficacy of interventions that reduce exposure to multiple parasite species. These findings can be generalized to many other infectious diseases, including human malaria, and illustrate how co-infections can play a key role in determining population-level patterns of morbidity and mortality due to parasite infections.

Signatures of positive selection in East African Shorthorn Zebu: A genome-wide single nucleotide polymorphism analysis.

The small East African Shorthorn Zebu (EASZ) is the main indigenous cattle across East Africa. A recent genome wide SNP analysis revealed an ancient stable African taurine x Asian zebu admixture. Here, we assess the presence of candidate signatures of positive selection in their genome, with the aim to provide qualitative insights about the corresponding selective pressures. Four hundred and twenty-five EASZ and four reference populations (Holstein-Friesian, Jersey, N'Dama and Nellore) were analysed using 46,171 SNPs covering all autosomes and the X chromosome. Following FST and two extended haplotype homozygosity-based (iHS and Rsb) analyses 24 candidate genome regions within 14 autosomes and the X chromosome were revealed, in which 18 and 4 were previously identified in tropical-adapted and commercial breeds, respectively. These regions overlap with 340 bovine QTL. They include 409 annotated genes, in which 37 were considered as candidates. These genes are involved in various biological pathways (e.g. immunity, reproduction, development and heat tolerance). Our results support that different selection pressures (e.g. environmental constraints, human selection, genome admixture constrains) have shaped the genome of EASZ. We argue that these candidate regions represent genome landmarks to be maintained in breeding programs aiming to improve sustainable livestock productivity in the tropics.

Genetic susceptibility to infectious disease in East African Shorthorn Zebu: a genome-wide analysis of the effect of heterozygosity and exotic introgression.

BACKGROUND: Positive multi-locus heterozygosity-fitness correlations have been observed in a number of natural populations. They have been explained by the correlation between heterozygosity and inbreeding, and the negative effect of inbreeding on fitness (inbreeding depression). Exotic introgression in a locally adapted population has also been found to reduce fitness (outbreeding depression) through the breaking-up of co-adapted genes, or the introduction of non-locally adapted gene variants. In this study we examined the inter-relationships between genome-wide heterozygosity, introgression, and death or illness as a result of infectious disease in a sample of calves from an indigenous population of East African Shorthorn Zebu (crossbred Bos taurus x Bos indicus) in western Kenya. These calves were observed from birth to one year of age as part of the Infectious Disease in East African Livestock (IDEAL) project. Some of the calves were found to be genetic hybrids, resulting from the recent introgression of European cattle breed(s) into the indigenous population. European cattle are known to be less well adapted to the infectious diseases present in East Africa. If death and illness as a result of infectious disease have a genetic basis within the population, we would expect both a negative association of these outcomes with introgression and a positive association with heterozygosity. RESULTS: In this indigenous livestock population we observed negative associations between heterozygosity and both death and illness as a result of infectious disease and a positive association between European taurine introgression and episodes of clinical illness. CONCLUSION: We observe the effects of both inbreeding and outbreeding depression in the East African Shorthorn Zebu, and therefore find evidence of a genetic component to vulnerability to infectious disease. These results indicate that the significant burden of infectious disease in this population could, in principle, be reduced by altered breeding practices.