ORCID Profile
0000-0002-4007-953X
Current Organisation
CanCan Diagnostics Ltd
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Publisher: Springer Science and Business Media LLC
Date: 17-02-2022
DOI: 10.1038/S41467-022-28605-0
Abstract: Despite only 8% of cattle being found in Europe, European breeds dominate current genetic resources. This adversely impacts cattle research in other important global cattle breeds, especially those from Africa for which genomic resources are particularly limited, despite their disproportionate importance to the continent’s economies. To mitigate this issue, we have generated assemblies of African breeds, which have been integrated with genomic data for 294 erse cattle into a graph genome that incorporates global cattle ersity. We illustrate how this more representative reference assembly contains an extra 116.1 Mb (4.2%) of sequence absent from the current Hereford sequence and consequently inaccessible to current studies. We further demonstrate how using this graph genome increases read mapping rates, reduces allelic biases and improves the agreement of structural variant calling with independent optical mapping data. Consequently, we present an improved, more representative, reference assembly that will improve global cattle research.
Publisher: Public Library of Science (PLoS)
Date: 19-08-2013
Publisher: Frontiers Media SA
Date: 29-09-2021
DOI: 10.3389/FVETS.2021.731238
Abstract: 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 (chi 2 = 4.00, p = 0.046), and days to peak temperature (chi 2 = 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 s les 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.
Publisher: Springer Science and Business Media LLC
Date: 23-05-2022
Publisher: Oxford University Press (OUP)
Date: 27-01-2021
DOI: 10.1093/GBE/EVAB014
Abstract: Great progress has been made over recent years in the identification of selection signatures in the genomes of livestock species. This work has primarily been carried out in commercial breeds for which the dominant selection pressures are associated with artificial selection. As agriculture and food security are likely to be strongly affected by climate change, a better understanding of environment-imposed selection on agricultural species is warranted. Ethiopia is an ideal setting to investigate environmental adaptation in livestock due to its wide variation in geo-climatic characteristics and the extensive genetic and phenotypic variation of its livestock. Here, we identified over three million single nucleotide variants across 12 Ethiopian sheep populations and applied landscape genomics approaches to investigate the association between these variants and environmental variables. Our results suggest that environmental adaptation for precipitation-related variables is stronger than that related to altitude or temperature, consistent with large-scale meta-analyses of selection pressure across species. The set of genes showing association with environmental variables was enriched for genes highly expressed in human blood and nerve tissues. There was also evidence of enrichment for genes associated with high-altitude adaptation although no strong association was identified with hypoxia-inducible-factor (HIF) genes. One of the strongest altitude-related signals was for a collagen gene, consistent with previous studies of high-altitude adaptation. Several altitude-associated genes also showed evidence of adaptation with temperature, suggesting a relationship between responses to these environmental factors. These results provide a foundation to investigate further the effects of climatic variables on small ruminant populations.
Publisher: Frontiers Media SA
Date: 05-11-2021
DOI: 10.3389/FCIMB.2021.751671
Abstract: Theileria parva is the causative agent of East Coast fever and Corridor disease, which are fatal, economically important diseases of cattle in eastern, central and southern Africa. Improved methods of control of the diseases are urgently required. The parasite transforms host lymphocytes, resulting in a rapid, clonal expansion of infected cells. Resistance to the disease has long been reported in cattle from T. parva -endemic areas. We reveal here that first- and second-generation descendants of a single Bos indicus bull survived severe challenge with T. parva , (overall survival rate 57.3% compared to 8.7% for unrelated animals) in a series of five field studies. Tolerant cattle displayed a delayed and less severe parasitosis and febrile response than unrelated animals. The in vitro proliferation of cells from surviving cattle was much reduced compared to those from animals that succumbed to infection. Additionally, some pro-inflammatory cytokines such as IL1β, IL6, TNFα or TGFβ which are usually strongly expressed in susceptible animals and are known to regulate cell growth or motility, remain low in tolerant animals. This correlates with the reduced proliferation and less severe clinical reactions observed in tolerant cattle. The results show for the first time that the inherited tolerance to T. parva is associated with decreased proliferation of infected lymphocytes. The results are discussed in terms of whether the reduced proliferation is the result of a perturbation of the transformation mechanism induced in infected cells or is due to an innate immune response present in the tolerant cattle.
Publisher: Springer Science and Business Media LLC
Date: 12-02-2020
DOI: 10.1186/S12915-020-0738-1
Abstract: Hybridisation and introgression play key roles in the evolutionary history of animal species. They are commonly observed within several orders in wild birds. The domestic chicken Gallus gallus domesticus is the most common livestock species. More than 65 billion chickens are raised annually to produce meat and 80 million metric tons of egg for global human consumption by the commercial sector. Unravelling the origin of its genetic ersity has major application for sustainable breeding improvement programmes. In this study, we report genome-wide analyses for signatures of introgression between indigenous domestic village chicken and the four wild Gallus species. We first assess the genome-wide phylogeny and ergence time across the genus Gallus . Genome-wide sequence ergence analysis supports a sister relationship between the Grey junglefowl G. sonneratii and Ceylon junglefowl G. lafayettii . Both species form a clade that is sister to the Red junglefowl G. gallus , with the Green junglefowl G. varius the most ancient lineage within the genus. We reveal extensive bidirectional introgression between the Grey junglefowl and the domestic chicken and to a much lesser extent with the Ceylon junglefowl. We identify a single case of Green junglefowl introgression. These introgressed regions include genes with biological functions related to development and immune system. Our study shows that while the Red junglefowl is the main ancestral species, introgressive hybridisation episodes have impacted the genome and contributed to the ersity of the domestic chicken, although likely at different levels across its geographic range.
Publisher: Public Library of Science (PLoS)
Date: 21-04-2022
DOI: 10.1371/JOURNAL.PGEN.1010099
Abstract: East Coast fever, a tick-borne cattle disease caused by the Theileria parva parasite, is among the biggest natural killers of cattle in East Africa, leading to over 1 million deaths annually. Here we report on the genetic analysis of a cohort of Bos indicus (Boran) cattle demonstrating heritable tolerance to infection with T . parva ( h 2 = 0.65, s.e. 0.57). Through a linkage analysis we identify a 6 Mb genomic region on bovine chromosome 15 that is significantly associated with survival outcome following T . parva exposure. Testing this locus in an independent cohort of animals replicates this association with survival following T . parva infection. A stop gained variant in a paralogue of the FAF1 gene in this region was found to be highly associated with survival across both related and unrelated animals, with only one of the 20 homozygote carriers (T/T) of this change succumbing to the disease in contrast to 44 out of 97 animals homozygote for the reference allele (C/C). Consequently, we present a genetic locus linked to tolerance of one of Africa’s most important cattle diseases, raising the promise of marker-assisted selection for cattle that are less susceptible to infection by T . parva .
Publisher: Public Library of Science (PLoS)
Date: 29-08-2013
DOI: 10.1371/ANNOTATION/2727DE85-899F-4104-955D-1C5F3C0D3319
Publisher: Springer Science and Business Media LLC
Date: 17-01-2020
DOI: 10.1038/S41467-019-13762-6
Abstract: The extent to which the impact of regulatory genetic variants may depend on other factors, such as the expression levels of upstream transcription factors, remains poorly understood. Here we report a framework in which regulatory variants are first aggregated into sets, and using these as estimates of the total cis-genetic effects on a gene we model their non-additive interactions with the expression of other genes in the genome. Using 1220 lymphoblastoid cell lines across platforms and independent datasets we identify 74 genes where the impact of their regulatory variant-set is linked to the expression levels of networks of distal genes. We show that these networks are predominantly associated with tumourigenesis pathways, through which immortalised cells are able to rapidly proliferate. We consequently present an approach to define gene interaction networks underlying important cellular pathways such as cell immortalisation.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Wragg.