4 results on '"Joseph E. Powell"'
Search Results
2. A locus conferring tolerance to Theileria infection in African cattle
- Author
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Oswald Matika, Tatjana Sitt, Musa A. Hassan, Johanneke D. Hemmink, Elizabeth J. Poole, B.M. deC. Bronsvoort, Eaj Cook, Andrea Talenti, David Wragg, P. Latre de Late, Antoinette Aluoch Miyunga, W. I. Morrison, Phil Toye, James Prendergast, Timothy Connelley, Joseph E. Powell, Stephen Mwaura, M. Chepkowny, Rebecca Callaby, Gideon Ndambuki, Edith Paxton, Karen Marshall, Liam J. Morrison, R. Njeru, and Harriet Auty
- Subjects
Veterinary medicine ,Cancer Research ,Theileriasis/genetics ,Theileria parva ,Theileria/genetics ,Cattle Diseases ,Locus (genetics) ,Adaptor Proteins, Signal Transducing/genetics ,Disease ,Cattle Diseases/genetics ,Theileria ,parasitic diseases ,Genetics ,Animals ,Humans ,East Coast fever ,Allele ,Boran cattle ,Molecular Biology ,Alleles ,Genetics (clinical) ,Ecology, Evolution, Behavior and Systematics ,Adaptor Proteins, Signal Transducing ,biology ,Theileria parva/genetics ,biology.organism_classification ,Theileriasis ,Apoptosis Regulatory Proteins/genetics ,Cattle ,Apoptosis Regulatory Proteins - Abstract
East Coast fever, a tick-borne cattle disease caused by theTheileria parvaparasite, 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 Boran cattle demonstrating heritable tolerance to infection byT. parva(h2= 0.65, s.e. 0.57). Through a linkage analysis we identify a 6 Mb genomic region onBos tauruschromosome 15 that is significantly associated with survival outcome followingT. parvaexposure. Testing this locus in an independent cohort of animals replicates this association with survival followingT. parvainfection. A stop gained polymorphism 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 byT. parva.Author SummaryMore than a million cattle die of East Coast fever in Africa each year, the impact of which disproportionately falls onto low-income, smallholder farmers. The lack of a widely accessible vaccine, heavy reliance on chemicals to control the tick vector and inadequate drug treatments means that new approaches for controlling the disease are urgently required. Through a genetic study of an extended pedigree of Boran cattle that are more than three times less likely to succumb to the disease than matched controls, we identify a region on chromosome 15 of the cattle genome associated with a high level of tolerance to the disease. We show that a variant in this region is also associated with survival in an independent cohort, and is linked to rates of cell expansion during infection. This genetic variant can therefore support marker-assisted selection, allowing farmers to breed tolerant cattle and offers a route to introduce this beneficial DNA to non-native breeds, enabling reduced disease incidence and increased productivity, which would be of benefit to millions of rural smallholder farmers across Africa.
- Published
- 2022
3. Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.
- Author
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Hannah Currant, Pirro Hysi, Tomas W Fitzgerald, Puya Gharahkhani, Pieter W M Bonnemaijer, Anne Senabouth, Alex W Hewitt, UK Biobank Eye and Vision Consortium, International Glaucoma Genetics Consortium, Denize Atan, Tin Aung, Jason Charng, Hélène Choquet, Jamie Craig, Peng T Khaw, Caroline C W Klaver, Michiaki Kubo, Jue-Sheng Ong, Louis R Pasquale, Charles A Reisman, Maciej Daniszewski, Joseph E Powell, Alice Pébay, Mark J Simcoe, Alberta A H J Thiadens, Cornelia M van Duijn, Seyhan Yazar, Eric Jorgenson, Stuart MacGregor, Chris J Hammond, David A Mackey, Janey L Wiggs, Paul J Foster, Praveen J Patel, Ewan Birney, and Anthony P Khawaja
- Subjects
Genetics ,QH426-470 - Abstract
Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.
- Published
- 2021
- Full Text
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4. Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data.
- Author
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Joseph E Powell, Anjali K Henders, Allan F McRae, Jinhee Kim, Gibran Hemani, Nicholas G Martin, Emmanouil T Dermitzakis, Greg Gibson, Grant W Montgomery, and Peter M Visscher
- Subjects
Genetics ,QH426-470 - Abstract
There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted--in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects.
- Published
- 2013
- Full Text
- View/download PDF
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