CTLGH health genetics program
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Item Clinical evaluation of corridor disease in Bos indicus (Boran) cattle naturally infected with buffalo-derived Theileria parva(Journal Article, 2021-09-29) Cook, Elizabeth A.J.; Sitt, Tatjana; Poole, Elizabeth J.; Ndambuki, Gideon M.; Mwaura, Stephen; Chepkwony, M.C.; Latré de Laté, Perle; Miyunga, Antoinette; Aardt, Richard van; Prettejohn, G.; Wragg, D.; Prendergast, J.G.D.; Morrison, W.I.; Toye, Philip G.Corridor disease (CD) is a fatal condition of cattle caused by buffalo-derived Theileria parva. Unlike the related condition, East Coast fever, which results from infection with cattle-derived T. parva, CD has not been extensively studied. We describe in detail the clinical and laboratory findings in cattle naturally infected with buffalo-derived T. parva. Forty-six cattle were exposed to buffalo-derived T. parva under field conditions at the Ol Pejeta Conservancy, Kenya, between 2013 and 2018. The first signs of disease observed in all animals were nasal discharge (mean day of onset was 9 days post-exposure), enlarged lymph nodes (10 days post-exposure), and pyrexia (13.7 days post-exposure). Coughing and labored breathing were observed in more than 50% of animals (14 days post-exposure). Less commonly observed signs, corneal edema (22%) and diarrhea (11%), were observed later in the disease progression (19 days post-exposure). All infections were considered clinically severe, and 42 animals succumbed to infection. The mean time to death across all studies was 18.4 days. The mean time from onset of clinical signs to death was 9 days and from pyrexia to death was 4.8 days, indicating a relatively short duration of clinical illness. There were significant relationships between days to death and the days to first temperature (chi2 = 4.00, p = 0.046), and days to peak temperature (chi2 = 25.81, p = 0.001), animals with earlier onset pyrexia died sooner. These clinical indicators may be useful for assessing the severity of disease in the future. All infections were confirmed by the presence of macroschizonts in lymph node biopsies (mean time to parasitosis was 11 days). Piroplasms were detected in the blood of two animals (4%) and 20 (43%) animals seroconverted. In this study, we demonstrate the successful approach to an experimental field study for CD in cattle. We also describe the clinical progression of CD in naturally infected cattle, including the onset and severity of clinical signs and pathology. Laboratory diagnoses based on examination of blood samples are unreliable, and alternatives may not be available to cattle keepers. The rapid development of CD requires recognition of the clinical signs, which may be useful for early diagnosis of the disease and effective intervention for affected animals.Item Integrating genetic and genomic analyses of combined health data across ecotypes to improve disease resistance in indigenous African chickens(Journal Article, 2020-10-09) Banos, Giorgios; Lindsay, V.; Desta, T.T.; Bettridge, Judy M.; Sánchez Molano, E.; Vallejo Trujillo, Adriana; Matika, O.; Dessie, Tadelle; Wigley, P.; Christley, Robert M.; Kaiser, P.; Hanotte, Olivier H.; Psifidi, A.Poultry play an important role in the agriculture of many African countries. The majority of chickens in sub-Saharan Africa are indigenous, raised in villages under semi-scavenging conditions. Vaccinations and biosecurity measures rarely apply, and infectious diseases remain a major cause of mortality and reduced productivity. Genomic selection for disease resistance offers a potentially sustainable solution but this requires sufficient numbers of individual birds with genomic and phenotypic data, which is often a challenge to collect in the small populations of indigenous chicken ecotypes. The use of information across-ecotypes presents an attractive possibility to increase the relevant numbers and the accuracy of genomic selection. In this study, we performed a joint analysis of two distinct Ethiopian indigenous chicken ecotypes to investigate the genomic architecture of important health and productivity traits and explore the feasibility of conducting genomic selection across-ecotype. Phenotypic traits considered were antibody response to Infectious Bursal Disease (IBDV), Marek's Disease (MDV), Fowl Cholera (PM) and Fowl Typhoid (SG), resistance to Eimeria and cestode parasitism, and productivity (body weight and body condition score (BCS)). Combined data from the two chicken ecotypes, Horro (n=384) and Jarso (n=376), were jointly analysed for genetic parameter estimation, genome-wide association studies (GWAS), genomic breeding value (GEBVs) calculation, genomic predictions, whole-genome sequencing (WGS), and pathways analyses. Estimates of across-ecotype heritability were significant and moderate in magnitude (0.22-0.47) for all traits except for SG and BCS. GWAS identified several significant genomic associations with health and productivity traits. The WGS analysis revealed putative candidate genes and mutations for IBDV (TOLLIP, ANGPTL5, BCL9, THEMIS2), MDV (GRM7), SG (MAP3K21), Eimeria (TOM1L1) and cestodes (TNFAIP1, ATG9A, NOS2) parasitism, which warrant further investigation. Reliability of GEBVs increased compared to within-ecotype calculations but accuracy of genomic prediction did not, probably because the genetic distance between the two ecotypes offset the benefit from increased sample size. However, for some traits genomic prediction was only feasible in across-ecotype analysis. Our results generally underpin the potential of genomic selection to enhance health and productivity across-ecotypes. Future studies should establish the required minimum sample size and genetic similarity between ecotypes to ensure accurate joint genomic selection.Item Reflections on IDEAL: What we have learnt from a unique calf cohort study(Journal Article, 2020-08) Callaby, R.; Jennings, A.; Mwangi, S.T.; Mbole-Kariuki, M.; Wyk, Ilana Conradie van; Kiara, Henry K.; Coetzer, Jacobus A.W.; Woolhouse, Mark E.J.; Hanotte, Olivier H.; Toye, Philip G.; Bronsvoort, B.M. de C.The year 2020 marks a decade since the final visit was made in the 'Infectious Diseases of East African Livestock' (IDEAL) project. However, data generation from samples obtained during this ambitious longitudinal study still continues. As the project launches its extensive open-access database and biobank to the scientific community, we reflect on the challenges overcome, the knowledge gained, and the advantages of such a project. We discuss the legacy of the IDEAL project and how it continues to generate evidence since being adopted by the Centre for Tropical Livestock Genetics and Health (CTLGH). We also examine the impact of the IDEAL project, from the authors perspective, for each of the stakeholders (the animal, the farmer, the consumer, the policy maker, the funding body, and the researcher and their institution) involved in the project and provide recommendations for future researchers who are interested in running longitudinal field studies.Item Mzima Cow Project: A transgenics approach to the basic mechanisms underlying trypanosome resistance(Poster, 2018-03-12) International Livestock Research InstituteItem Mzima Cow Project: A transgenics approach to introducing resistance to trypanosomiasis translating genetic research to adoption and social value(Poster, 2018-03-12) International Livestock Research InstituteItem Cloning of the African indigenous cattle breed Kenyan Boran(Journal Article, 2016-08) Mingyan Yu; Muteti, C.; Ogugo, M.; Ritchie, W.A.; Raper, J.; Kemp, Stephen J.Kenyan Boran, an indigenous East African zebu (Bos indicus) breed, is kept mostly for beef production in semiarid areas of Kenya.1 The breed is well adapted to high ambient temperature, poor quality feed and high disease challenges compared to European exotic Bos taurus breeds.2 However, they are susceptible to African tsetse fly-transmitted trypanosomiasis (ATT) caused by parasites (Trypanosoma spp.), which are also the cause of human African trypanosomiasis or sleeping sickness. The ATT is a major constraint to livestock production in sub-Saharan Africa.3 It is known that serum from baboons kills both animal- and human-infective African trypanosomes through serum trypanosome lytic factors (TLFs).4 The generation of trypanosomiasis-resistant transgenic cattle carrying baboon-derived TLFs may have the potential to improve livestock productivity in Kenya and Africa.4 As a precursor to such a study, we cloned a Kenyan Boran bull by somatic cell nuclear transfer (SCNT) using primary embryonic fibroblasts. This successful cloning represents an important first step towards the establishment of genetically modified Kenyan Boran through SCNT with genome-modified fibroblasts. Boran embryonic fibroblasts were isolated from a 3-month-old male Kenyan Boran foetus and cultured with DMEM+10% FBS. Karyotyping was performed to confirm that the cell line had no major chromosome anomaly. Nuclei from an early passage (P6) of the fibroblasts were used for SCNT into oocytes aspirated from the ovaries of B. indicus cattle after slaughter. SCNT was performed as described,5 and the reconstructed blastocysts were transferred to suitable surrogate mothers. Around 273 days post-embryo transfer, a cloned calf was born by caesarean section operation after dexamethasone induction. Ten microsatellite markers (Table S1) were used to verify the parentage of the cloned calf and its offspring. In total, three cloned embryos (60%) aborted by the second trimester, and two cloned calves (40%) were born (Table S2). Both of the born calves showed a low blood glucose level (<30 mg/dl) and difficulty in standing alone with tendon laxity at birth. The first cloned calf died apparently due to low blood glucose. The second cloned calf was supplemented with 2.5 g glucose through the jugular vein within 8 h of birth followed by abdominal injection of glucose solution (5%) when the glucose level fell below 50 mg/dl.6 The blood glucose level and the tendon laxity normalised after 1 week, and the calf remained healthy afterwards. Two calves were born after introducing the cloned bull to a female Boran herd (Fig. 1). Genotyping confirmed that both of the calves were offspring of the cloned bull. With the boom of genome editing tools, for example transcription activator-like effector nucleases and clustered regularly interspaced short palindromic repeats/Cas9, there are unprecedented opportunities for improving livestock genetics efficiently through the introduction of superior traits between breeds by precise genome modification. The successful cloning of a Kenyan Boran bull has opened the possibility of making genetically modified Kenyan Boran with foreign genes or desired traits through genome editing at the fibroblast level followed by SCNT. None of the authors have any conflict of interest to declare. Table S1 Microsatellite markers used for parentage identification of the cloned calf and its offspring Table S2 Summary of somatic cell nuclear transfer with Boran embryonic fibroblasts Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.