25 results on '"Prendergast, James G D"'
Search Results
2. Profiling the immune epigenome across global cattle breeds
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Powell, Jessica, Talenti, Andrea, Fisch, Andressa, Hemmink, Johanneke D., Paxton, Edith, Toye, Philip, Santos, Isabel, Ferreira, Beatriz R., Connelley, Tim K., Morrison, Liam J., and Prendergast, James G. D.
- Published
- 2023
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3. The conservation of human functional variants and their effects across livestock species
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Zhao, Rongrong, Talenti, Andrea, Fang, Lingzhao, Liu, Shuli, Liu, George, Chue Hong, Neil P., Tenesa, Albert, Hassan, Musa, and Prendergast, James G. D.
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- 2022
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4. Assessment of genotyping array performance for genome-wide association studies and imputation in African cattle
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Riggio, Valentina, Tijjani, Abdulfatai, Callaby, Rebecca, Talenti, Andrea, Wragg, David, Obishakin, Emmanuel T., Ezeasor, Chukwunonso, Jongejan, Frans, Ogo, Ndudim I., Aboagye-Antwi, Fred, Toure, Alassane, Nzalawahej, Jahashi, Diallo, Boubacar, Missohou, Ayao, Belem, Adrien M. G., Djikeng, Appolinaire, Juleff, Nick, Fourie, Josephus, Labuschagne, Michel, Madder, Maxime, Marshall, Karen, Prendergast, James G. D., and Morrison, Liam J.
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- 2022
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5. Using machine learning to detect the differential usage of novel gene isoforms
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Zhang, Xiaopu, Hassan, Musa A., and Prendergast, James G. D.
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- 2022
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6. Investigating the origin and authenticity of Victoria Cross medals using X-ray fluorescence spectrometry
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Marriott, Andrew and Prendergast, James G. D.
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- 2020
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7. Whole genome analysis of water buffalo and global cattle breeds highlights convergent signatures of domestication
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Dutta, Prasun, Talenti, Andrea, Young, Rachel, Jayaraman, Siddharth, Callaby, Rebecca, Jadhav, Santosh Kumar, Dhanikachalam, Velu, Manikandan, Mayakannan, Biswa, Bhim B., Low, Wai Y., Williams, John L., Cook, Elizabeth, Toye, Phil, Wall, Eileen, Djikeng, Appolinaire, Marshall, Karen, Archibald, Alan L., Gokhale, Suresh, Kumar, Satish, Hume, David A., and Prendergast, James G. D.
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- 2020
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8. Meta-analysis of heritability estimates and genome-wide association for tick-borne haemoparasites in African cattle.
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Riggio, Valentina, Madder, Maxime, Labuschagne, Michel, Callaby, Rebecca, Rongrong Zhao, Djikeng, Appolinaire, Fourie, Josephus, Prendergast, James G. D., and Morrison, Liam J.
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HERITABILITY ,GENOME-wide association studies ,TICK control ,ANAPLASMA marginale ,CATTLE ,DISEASE resistance of plants ,BODY weight ,TICK infestations - Abstract
The control of tick-borne haemoparasites in cattle largely relies on the use of acaricide drugs against the tick vectors, with some vaccination also being used against selected pathogens. These interventions can be difficult in Africa, where accessibility and cost of vaccines can be issues, and the increasing resistance of tick vectors to the widely used acaricides is a complication to disease control. A potential complementary control strategy could be the exploitation of any natural host genetic resistance to the pathogens. However, there are currently very few estimates of the extent of host resistance to tick-borne haemoparasites, and a significant contributing factor to this knowledge gap is likely to be the difficulty of collecting appropriate samples and data in the smallholder systems that predominate livestock production in low- and middle-income countries, particularly at scale. In this study, we have estimated the heritability for the presence/absence of several important haemoparasite species (including Anaplasma marginale, Babesia bigemina, Babesia bovis, and Ehrlichia ruminantium), as well as for relevant traits such as body weight and body condition score (BCS), in 1,694 cattle from four African countries (Burkina Faso, Ghana, Nigeria, and Tanzania). Heritability estimates within countries were mostly not significant, ranging from 0.05 to 0.84 across traits and countries, with standard errors between 0.07 and 0.91. However, the weighted mean of heritability estimates was moderate and significant for body weight and BCS (0.40 and 0.49, respectively), with significant heritabilities also observed for the presence of A. marginale (0.16) and E. ruminantium (0.19). In a meta-analysis of genome-wide association studies (GWAS) for these traits, two peaks were identified as reaching the suggestive significance threshold (p < 1.91 × 10
−7 and p < 1.89 × 10−7 , respectively): one on chromosome 24 for BCS and one on chromosome 8 for the E. ruminantium infection status. These findings indicate that there is likely to be a genetic basis that contributes to pathogen presence/absence for tick-borne haemoparasite species, which could potentially be exploited to improve cattle resistance in Africa to the economically important diseases caused by these pathogens. [ABSTRACT FROM AUTHOR]- Published
- 2023
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9. Rare genetic variants underlie outlying levels of DNA methylation and gene-expression.
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Chundru, V Kartik, Marioni, Riccardo E, Prendergast, James G D, Lin, Tian, Beveridge, Allan J, Martin, Nicholas G, Montgomery, Grant W, Hume, David A, Deary, Ian J, Visscher, Peter M, Wray, Naomi R, and McRae, Allan F
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- 2023
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10. A promoter-level mammalian expression atlas
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Forrest, Alistair R. R., Kawaji, Hideya, Rehli, Michael, Kenneth Baillie, J., de Hoon, Michiel J. L., Haberle, Vanja, Lassmann, Timo, Kulakovskiy, Ivan V., Lizio, Marina, Itoh, Masayoshi, Andersson, Robin, Mungall, Christopher J., Meehan, Terrence F., Schmeier, Sebastian, Bertin, Nicolas, Jørgensen, Mette, Dimont, Emmanuel, Arner, Erik, Schmidl, Christian, Schaefer, Ulf, Medvedeva, Yulia A., Plessy, Charles, Vitezic, Morana, Severin, Jessica, Semple, Colin A., Ishizu, Yuri, Young, Robert S., Francescatto, Margherita, Alam, Intikhab, Albanese, Davide, Altschuler, Gabriel M., Arakawa, Takahiro, Archer, John A. C., Arner, Peter, Babina, Magda, Rennie, Sarah, Balwierz, Piotr J., Beckhouse, Anthony G., Pradhan-Bhatt, Swati, Blake, Judith A., Blumenthal, Antje, Bodega, Beatrice, Bonetti, Alessandro, Briggs, James, Brombacher, Frank, Maxwell Burroughs, A., Califano, Andrea, Cannistraci, Carlo V., Carbajo, Daniel, Chen, Yun, Chierici, Marco, Ciani, Yari, Clevers, Hans C., Dalla, Emiliano, Davis, Carrie A., Detmar, Michael, Diehl, Alexander D., Dohi, Taeko, Drabløs, Finn, Edge, Albert S. B., Edinger, Matthias, Ekwall, Karl, Endoh, Mitsuhiro, Enomoto, Hideki, Fagiolini, Michela, Fairbairn, Lynsey, Fang, Hai, Farach-Carson, Mary C., Faulkner, Geoffrey J., Favorov, Alexander V., Fisher, Malcolm E., Frith, Martin C., Fujita, Rie, Fukuda, Shiro, Furlanello, Cesare, Furuno, Masaaki, Furusawa, Jun-ichi, Geijtenbeek, Teunis B., Gibson, Andrew P., Gingeras, Thomas, Goldowitz, Daniel, Gough, Julian, Guhl, Sven, Guler, Reto, Gustincich, Stefano, Ha, Thomas J., Hamaguchi, Masahide, Hara, Mitsuko, Harbers, Matthias, Harshbarger, Jayson, Hasegawa, Akira, Hasegawa, Yuki, Hashimoto, Takehiro, Herlyn, Meenhard, Hitchens, Kelly J., Ho Sui, Shannan J., Hofmann, Oliver M., Hoof, Ilka, Hori, Fumi, Huminiecki, Lukasz, Iida, Kei, Ikawa, Tomokatsu, Jankovic, Boris R., Jia, Hui, Joshi, Anagha, Jurman, Giuseppe, Kaczkowski, Bogumil, Kai, Chieko, Kaida, Kaoru, Kaiho, Ai, Kajiyama, Kazuhiro, Kanamori-Katayama, Mutsumi, Kasianov, Artem S., Kasukawa, Takeya, Katayama, Shintaro, Kato, Sachi, Kawaguchi, Shuji, Kawamoto, Hiroshi, Kawamura, Yuki I., Kawashima, Tsugumi, Kempfle, Judith S., Kenna, Tony J., Kere, Juha, Khachigian, Levon M., Kitamura, Toshio, Peter Klinken, S., Knox, Alan J., Kojima, Miki, Kojima, Soichi, Kondo, Naoto, Koseki, Haruhiko, Koyasu, Shigeo, Krampitz, Sarah, Kubosaki, Atsutaka, Kwon, Andrew T., Laros, Jeroen F. J., Lee, Weonju, Lennartsson, Andreas, Li, Kang, Lilje, Berit, Lipovich, Leonard, Mackay-sim, Alan, Manabe, Ri-ichiroh, Mar, Jessica C., Marchand, Benoit, Mathelier, Anthony, Mejhert, Niklas, Meynert, Alison, Mizuno, Yosuke, de Lima Morais, David A., Morikawa, Hiromasa, Morimoto, Mitsuru, Moro, Kazuyo, Motakis, Efthymios, Motohashi, Hozumi, Mummery, Christine L., Murata, Mitsuyoshi, Nagao-Sato, Sayaka, Nakachi, Yutaka, Nakahara, Fumio, Nakamura, Toshiyuki, Nakamura, Yukio, Nakazato, Kenichi, van Nimwegen, Erik, Ninomiya, Noriko, Nishiyori, Hiromi, Noma, Shohei, Nozaki, Tadasuke, Ogishima, Soichi, Ohkura, Naganari, Ohmiya, Hiroko, Ohno, Hiroshi, Ohshima, Mitsuhiro, Okada-Hatakeyama, Mariko, Okazaki, Yasushi, Orlando, Valerio, Ovchinnikov, Dmitry A., Pain, Arnab, Passier, Robert, Patrikakis, Margaret, Persson, Helena, Piazza, Silvano, Prendergast, James G. D., Rackham, Owen J. L., Ramilowski, Jordan A., Rashid, Mamoon, Ravasi, Timothy, Rizzu, Patrizia, Roncador, Marco, Roy, Sugata, Rye, Morten B., Saijyo, Eri, Sajantila, Antti, Saka, Akiko, Sakaguchi, Shimon, Sakai, Mizuho, Sato, Hiroki, Satoh, Hironori, Savvi, Suzana, Saxena, Alka, Schneider, Claudio, Schultes, Erik A., Schulze-Tanzil, Gundula G., Schwegmann, Anita, Sengstag, Thierry, Sheng, Guojun, Shimoji, Hisashi, Shimoni, Yishai, Shin, Jay W., Simon, Christophe, Sugiyama, Daisuke, Sugiyama, Takaaki, Suzuki, Masanori, Suzuki, Naoko, Swoboda, Rolf K., ’t Hoen, Peter A. C., Tagami, Michihira, Takahashi, Naoko, Takai, Jun, Tanaka, Hiroshi, Tatsukawa, Hideki, Tatum, Zuotian, Thompson, Mark, Toyoda, Hiroo, Toyoda, Tetsuro, Valen, Eivind, van de Wetering, Marc, van den Berg, Linda M., Verardo, Roberto, Vijayan, Dipti, Vorontsov, Ilya E., Wasserman, Wyeth W., Watanabe, Shoko, Wells, Christine A., Winteringham, Louise N., Wolvetang, Ernst, Wood, Emily J., Yamaguchi, Yoko, Yamamoto, Masayuki, Yoneda, Misako, Yonekura, Yohei, Yoshida, Shigehiro, Zabierowski, Susan E., Zhang, Peter G., Zhao, Xiaobei, Zucchelli, Silvia, Summers, Kim M., Suzuki, Harukazu, Daub, Carsten O., Kawai, Jun, Heutink, Peter, Hide, Winston, Freeman, Tom C., Lenhard, Boris, Bajic, Vladimir B., Taylor, Martin S., Makeev, Vsevolod J., Sandelin, Albin, Hume, David A., Carninci, Piero, and Hayashizaki, Yoshihide
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- 2014
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11. Inherited Tolerance in Cattle to the Apicomplexan Protozoan Theileria parva is Associated with Decreased Proliferation of Parasite-Infected Lymphocytes.
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Latre de Late, Perle, Cook, Elizabeth A. J., Wragg, David, Poole, E. Jane, Ndambuki, Gideon, Miyunga, Antoinette Aluoch, Chepkwony, Maurine C., Mwaura, Stephen, Ndiwa, Nicholas, Prettejohn, Giles, Sitt, Tatjana, Van Aardt, Richard, Morrison, W. Ivan, Prendergast, James G. D., and Toye, Philip
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THEILERIA parva ,CATTLE ,OVERALL survival ,LYMPHOCYTES ,ZEBUS ,APICOMPLEXA ,PARASITES - 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. [ABSTRACT FROM AUTHOR]
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- 2021
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12. A genome-wide screen in human embryonic stem cells reveals novel sites of allele-specific histone modification associated with known disease loci
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Prendergast James G D, Tong Pin, Hay David C, Farrington Susan M, and Semple Colin A M
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Genetics ,QH426-470 - Abstract
Abstract Background Chromatin structure at a given site can differ between chromosome copies in a cell, and such imbalances in chromatin structure have been shown to be important in understanding the molecular mechanisms controlling several disease loci. Human genetic variation, DNA methylation, and disease have been intensely studied, uncovering many sites of allele-specific DNA methylation (ASM). However, little is known about the genome-wide occurrence of sites of allele-specific histone modification (ASHM) and their relationship to human disease. The aim of this study was to investigate the extent and characteristics of sites of ASHM in human embryonic stem cells (hESCs). Results Using a statistically rigorous protocol, we investigated the genomic distribution of ASHM in hESCs, and their relationship to sites of allele-specific expression (ASE) and DNA methylation. We found that, although they were rare, sites of ASHM were substantially enriched at loci displaying ASE. Many were also found at known imprinted regions, hence sites of ASHM are likely to be better markers of imprinted regions than sites of ASM. We also found that sites of ASHM and ASE in hESCs colocalize at risk loci for developmental syndromes mediated by deletions, providing insights into the etiology of these disorders. Conclusion These results demonstrate the potential importance of ASHM patterns in the interpretation of disease loci, and the protocol described provides a basis for similar studies of ASHM in other cell types to further our understanding of human disease susceptibility.
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- 2012
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13. Whole-Genome Sequence Data Suggest Environmental Adaptation of Ethiopian Sheep Populations.
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Wiener, Pamela, Robert, Christelle, Ahbara, Abulgasim, Salavati, Mazdak, Abebe, Ayele, Kebede, Adebabay, Wragg, David, Friedrich, Juliane, Vasoya, Deepali, Hume, David A, Djikeng, Appolinaire, Watson, Mick, Prendergast, James G D, Hanotte, Olivier, Mwacharo, Joram M, and Clark, Emily L
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GENES ,SHEEP ,NERVE tissue ,BODY temperature regulation ,SHEEP breeding ,ALTITUDES ,TREE growth - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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14. Linked Mutations at Adjacent Nucleotides Have Shaped Human Population Differentiation and Protein Evolution.
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Prendergast, James G D, Pugh, Carys, Harris, Sarah E, Hume, David A, Deary, Ian J, and Beveridge, Allan
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POPULATION , *POPULATION differentiation , *HUMAN genome , *NUCLEOTIDES , *HUMAN evolution - Abstract
Despite the fundamental importance of single nucleotide polymorphisms (SNPs) to human evolution, there are still large gaps in our understanding of the forces that shape their distribution across the genome. SNPs have been shown to not be distributed evenly, with directly adjacent SNPs found unusually frequently. Why this is the case is unclear. We illustrate how neighboring SNPs that cannot be explained by a single mutation event (that we term here sequential dinucleotide mutations [SDMs]) are driven by distinct processes to SNPs and multinucleotide polymorphisms (MNPs). By studying variation across populations, including a novel cohort of 1,358 Scottish genomes, we show that, SDMs are over twice as common as MNPs and like SNPs display distinct mutational spectra across populations. These biases are not only different to those observed among SNPs and MNPs but are also more divergent between human population groups. We show that the changes that make up SDMs are not independent and identify a distinct mutational profile, CA → CG → TG, that is observed an order of magnitude more often than expected from background SNP rates and the numbers of other SDMs involving the gain and deamination of CpG sites. Intriguingly particular pathways through the amino acid code appear to have been favored relative to that expected from intergenic SDM rates and the occurrences of coding SNPs, and in particular those that lead to the creation of single codon amino acids. We finally present evidence that epistatic selection has potentially disfavored sequential nonsynonymous changes in the human genome. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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15. Shared regulatory sites are abundant in the human genome and shed light on genome evolution and disease pleiotropy.
- Author
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Tong, Pin, Monahan, Jack, and Prendergast, James G. D.
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GENE expression ,HUMAN genome ,CHROMATIN ,PHENOTYPES ,GENETIC pleiotropy - Abstract
Large-scale gene expression datasets are providing an increasing understanding of the location of cis-eQTLs in the human genome and their role in disease. However, little is currently known regarding the extent of regulatory site-sharing between genes. This is despite it having potentially wide-ranging implications, from the determination of the way in which genetic variants may shape multiple phenotypes to the understanding of the evolution of human gene order. By first identifying the location of non-redundant cis-eQTLs, we show that regulatory site-sharing is a relatively common phenomenon in the human genome, with over 10% of non-redundant regulatory variants linked to the expression of multiple nearby genes. We show that these shared, local regulatory sites are linked to high levels of chromatin looping between the regulatory sites and their associated genes. In addition, these co-regulated gene modules are found to be strongly conserved across mammalian species, suggesting that shared regulatory sites have played an important role in shaping human gene order. The association of these shared cis-eQTLs with multiple genes means they also appear to be unusually important in understanding the genetics of human phenotypes and pleiotropy, with shared regulatory sites more often linked to multiple human phenotypes than other regulatory variants. This study shows that regulatory site-sharing is likely an underappreciated aspect of gene regulation and has important implications for the understanding of various biological phenomena, including how the two and three dimensional structures of the genome have been shaped and the potential causes of disease pleiotropy outside coding regions. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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16. Multiple Common Susceptibility Variants near BMP Pathway Loci GREM1, BMP4, and BMP2 Explain Part of the Missing Heritability of Colorectal Cancer.
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Tomlinson, Ian P. M., Carvajal-Carmona, Luis G., Dobbins, Sara E., Tenesa, Albert, Jones, Angela M., Howarth, Kimberley, Palles, Claire, Broderick, Peter, Jaeger, Emma E. M., Farrington, Susan, Lewis, Annabelle, Prendergast, James G. D., Pittman, Alan M., Theodoratou, Evropi, Olver, Bianca, Walker, Marion, Penegar, Steven, Barclay, Ella, Whiffin, Nicola, and Martin, Lynn
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GENETICS of colon cancer ,GENETIC polymorphisms ,LOCUS (Genetics) ,BONE morphogenetic proteins ,HERITABILITY ,GENETICS of disease susceptibility ,GENE frequency - Abstract
Genome-wide association studies (GWAS) have identified 14 tagging single nucleotide polymorphisms (tagSNPs) that are associated with the risk of colorectal cancer (CRC), and several of these tagSNPs are near bone morphogenetic protein (BMP) pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3), BMP4 (14q22.2), and BMP2 (20p12.3) using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93x10
-10 ) and BMP2 (rs4813802, P = 4.65x10-11 ). Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33x10-8 ) and rs11632715 (P = 2.30x10-10 ). As low-penetrance predisposition variants become harder to identify -- owing to small effect sizes and/or low risk allele frequencies -- approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases. [ABSTRACT FROM AUTHOR]- Published
- 2011
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17. Sequencing Illustrates the Transcriptional Response of Legionella pneumophila during Infection and Identifies Seventy Novel Small Non-Coding RNAs.
- Author
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Weissenmayer, Barbara A., Prendergast, James G. D., Lohan, Amanda J., and Loftus, Brendan J.
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SECOND harmonic generation , *RNA , *HOST-parasite relationships , *ACANTHAMOEBA castellanii , *MACROPHAGES , *GENE expression - Abstract
Second generation sequencing has prompted a number of groups to re-interrogate the transcriptomes of several bacterial and archaeal species. One of the central findings has been the identification of complex networks of small non-coding RNAs that play central roles in transcriptional regulation in all growth conditions and for the pathogen's interaction with and survival within host cells. Legionella pneumophila is a Gram-negative facultative intracellular human pathogen with a distinct biphasic lifestyle. One of its primary environmental hosts in the free-living amoeba Acanthamoeba castellanii and its infection by L. pneumophila mimics that seen in human macrophages. Here we present analysis of strand specific sequencing of the transcriptional response of L. pneumophila during exponential and post-exponential broth growth and during the replicative and transmissive phase of infection inside A. castellanii. We extend previous microarray based studies as well as uncovering evidence of a complex regulatory architecture underpinned by numerous non-coding RNAs. Over seventy new non-coding RNAs could be identified; many of them appear to be strain specific and in configurations not previously reported. We discover a family of non-coding RNAs preferentially expressed during infection conditions and identify a second copy of 6S RNA in L. pneumophila. We show that the newly discovered putative 6S RNA as well as a number of other non-coding RNAs show evidence for antisense transcription. The nature and extent of the non-coding RNAs and their expression patterns suggests that these may well play central roles in the regulation of Legionella spp. specific traits and offer clues as to how L. pneumophila adapts to its intracellular niche. The expression profiles outlined in the study have been deposited into Genbank's Gene Expression Omnibus (GEO) database under the series accession GSE27232. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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18. Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33.
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Houlston, Richard S., Cheadle, Jeremy, Dobbins, Sara E., Tenesa, Albert, Jones, Angela M., Howarth, Kimberley, Spain, Sarah L., Broderick, Peter, Domingo, Enric, Farrington, Susan, Prendergast, James G. D., Pittman, Alan M., Theodoratou, Evi, Smith, Christopher G., Olver, Bianca, Walther, Axel, Barnetson, Rebecca A., Churchman, Michael, Jaeger, Emma E. M., and Penegar, Steven
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GENETICS ,GENOMES ,META-analysis ,DISEASE susceptibility ,COLON cancer - Abstract
Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10
−10 and rs6687758, OR = 1.09, P = 2.27 × 10−9 ), 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10−8 ), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10−10 and rs7136702, OR = 1.06, P = 4.02 × 10−8 ) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10−10 ). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered. [ABSTRACT FROM AUTHOR]- Published
- 2010
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19. hapbin: An Efficient Program for Performing Haplotype-Based Scans for Positive Selection in Large Genomic Datasets.
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Maclean, Colin A., Hong, Neil P. Chue, and Prendergast, James G. D.
- Abstract
Understanding how the genome is shaped by selective processes forms an integral part of modern biology. However, as genomic datasets continue to grow larger it is becoming increasingly difficult to apply traditional statistics for detecting signatures of selection to these cohorts. There is therefore a pressing need for the development of the next generation of computational and analytical tools for detecting signatures of selection in large genomic datasets. Here, we present hapbin, an efficient multithreaded implementation of extended haplotype homzygosity-based statistics for detecting selection, which is up to 3,400 times faster than the current fastest implementations of these algorithms. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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20. Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21.
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Tenesa, Albert, Farrington, Susan M., Prendergast, James G. D., Porteous, Mary E., Walker, Marion, Haq, Naila, Barnetson, Rebecca A., Theodoratou, Evropi, Cetnarskyj, Roseanne, Cartwright, Nicola, Semple, Colin, Clark, Andrew J., Reid, Fiona J. L., Smith, Lorna A., Kavoussanakis, Kostas, Koessler, Thibaud, Pharoah, Paul D. P., Buch, Stephan, Schafmayer, Clemens, and Tepel, Jürgen
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COLON cancer ,GENOMES ,ETIOLOGY of cancer ,ETIOLOGY of diseases ,BIOLOGICAL variation ,GENETIC research - Abstract
In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 × 10
−10 ), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 × 10−26 ) and 18q21 (rs4939827; OR = 1.2; P = 7.8 × 10−28 ). Risk was greater for rectal than for colon cancer for rs3802842 (P < 0.008) and rs4939827 (P < 0.009). Carrying all six possible risk alleles yielded OR = 2.6 (95% CI = 1.75–3.89) for CRC. These findings extend our understanding of the role of common genetic variation in CRC etiology. [ABSTRACT FROM AUTHOR]- Published
- 2008
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21. Chromatin structure and evolution in the human genome.
- Author
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Prendergast, James G. D., Campbell, Harry, Gilbert, Nick, Dunlop, Malcolm G., Bickmore, Wendy A., and Semple, Colin A. M.
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CHROMATIN , *GENOMES , *GENES , *CHROMOSOMES , *DNA damage - Abstract
Background: Evolutionary rates are not constant across the human genome but genes in close proximity have been shown to experience similar levels of divergence and selection. The higher-order organisation of chromosomes has often been invoked to explain such phenomena but previously there has been insufficient data on chromosome structure to investigate this rigorously. Using the results of a recent genome-wide analysis of open and closed human chromatin structures we have investigated the global association between divergence, selection and chromatin structure for the first time. Results: In this study we have shown that, paradoxically, synonymous site divergence (dS) at non-CpG sites is highest in regions of open chromatin, primarily as a result of an increased number of transitions, while the rates of other traditional measures of mutation (intergenic, intronic and ancient repeat divergence as well as SNP density) are highest in closed regions of the genome. Analysis of human-chimpanzee divergence across intron-exon boundaries indicates that although genes in relatively open chromatin generally display little selection at their synonymous sites, those in closed regions show markedly lower divergence at their fourfold degenerate sites than in neighbouring introns and intergenic regions. Exclusion of known Exonic Splice Enhancer hexamers has little affect on the divergence observed at fourfold degenerate sites across chromatin categories; however, we show that closed chromatin is enriched with certain classes of ncRNA genes whose RNA secondary structure may be particularly important. Conclusion: We conclude that, overall, non-CpG mutation rates are lowest in open regions of the genome and that regions of the genome with a closed chromatin structure have the highest background mutation rate. This might reflect lower rates of DNA damage or enhanced DNA repair processes in regions of open chromatin. Our results also indicate that dS is a poor measure of mutation rates, particularly when used in closed regions of the genome, as genes in closed regions generally display relatively strong levels of selection at their synonymous sites. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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22. Side Effects: Substantial Non-Neutral Evolution Flanking Regulatory Sites
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Prendergast, James G. D. and Semple, Colin A.
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MAMMAL genomes , *HUMAN genome , *MAMMAL genetics , *GENOMES , *GENETICS - Abstract
The article explores the structure of the genome within cells in mammals and humans. It notes that between 5% and 15% of the genome in mammals is evolutionarily constrained and is presumably functional. It cites the discovery that the physical organization and structure of the genome within cells casts discernable shadows on the sequence. Researchers also found a large gap between the proportion of the genome thought to be functional.
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- 2013
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23. Examining the Impact of Imputation Errors on Fine-Mapping Using DNA Methylation QTL as a Model Trait.
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Chundru, V. Kartik, Marioni, Riccardo E., Prendergast, James G. D., Vallerga, Costanza L., Tian Lin, Beveridge, Allan J., Gratten, Jacob, Hume, David A., Deary, Ian J., Wray, Naomi R., Visscher, Peter M., and McRae, Allan F.
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NUCLEOTIDE analysis , *GENETIC polymorphisms , *GENOMES , *PAPER chromatography , *PROBABILITY theory , *STATISTICS , *DATA analysis , *DNA methylation , *HAPLOTYPES , *SEQUENCE analysis ,RESEARCH evaluation - Abstract
Genetic variants disrupting DNA methylation at CpG dinucleotides (CpG-SNP) provide a set of known causal variants to serve as models to test fine-mapping methodology. We use 1716 CpG-SNPs to test three fine-mapping approaches (Bayesian imputation-based association mapping, Bayesian sparse linear mixed model, and the J-test), assessing the impact of imputation errors and the choice of reference panel by using both whole-genome sequence (WGS), and genotype array data on the same individuals (n = 1166). The choice of imputation reference panel had a strong effect on imputation accuracy, with the 1000 Genomes Project Phase 3 (1000G) reference panel (n = 2504 from 26 populations) giving a mean nonreference discordance rate between imputed and sequenced genotypes of 3.2% compared to 1.6% when using the Haplotype Reference Consortium (HRC) reference panel (n = 32,470 Europeans). These imputation errors had an impact on whether the CpG-SNP was included in the 95% credible set, with a difference of ~23% and ~7% between the WGS and the 1000G and HRC imputed datasets, respectively. All of the fine-mapping methods failed to reach the expected 95% coverage of the CpG-SNP. This is attributed to secondary cis genetic effects that are unable to be statistically separated from the CpG-SNP, and through a masking mechanism where the effect of the methylation disrupting allele at the CpG-SNP is hidden by the effect of a nearby SNP that has strong linkage disequilibrium with the CpG-SNP. The reduced accuracy in fine-mapping a known causal variant in a low-level biological trait with imputed genetic data has implications for the study of higher-order complex traits and disease. [ABSTRACT FROM AUTHOR]
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- 2019
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24. Widespread signatures of recent selection linked to nucleosome positioning in the human lineage.
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Prendergast, James G. D. and Semple, Colin A. M.
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CHROMATIN , *NUCLEOTIDE sequence , *GENOMES , *EXONS (Genetics) , *DISEASES - Abstract
In this study we investigated the strengths and modes of selection associated with nucleosome positioning in the human lineage through the comparison of interspecies and intraspecies rates of divergence. We identify significant evidence for both positive and negative selection linked to human nucleosome positioning for the first time, implicating a widespread and important role for DNA sequence in the location of well-positioned nucleosomes. Selection appears to be acting on particular base substitutions to maintain optimum GC compositions in core and linker regions, with, e.g., unexpectedly elevated rates of C→T substitutions during recent human evolution at linker regions 60-90 bp from the nucleosome dyad but significant depletion of the same substitutions within nucleosome core regions. These patterns are strikingly consistent with the known relationships between genomic sequence composition and nucleosome assembly. By stratifying nucleosomes according to the GC content of their genomic neighborhood, we also show that the strength and direction of selection detected is dictated by local GC content. Intriguingly these signatures of selection are not restricted to nucleosomes in close proximity to exons, suggesting the correct positioning of nucleosomes is not only important in and around coding regions. This analysis provides strong evidence that the genomic sequences associated with nucleosomes are not evolving neutrally, and suggests that underlying DNA sequence is an important factor in nucleosome positioning. Recent signatures of selection linked to genomic features as ubiquitous as the nucleosome have important implications for human genome evolution and disease [ABSTRACT FROM AUTHOR]
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- 2011
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25. Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed.
- Author
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Pugh, Carys A., Farrell, Lindsay L., Carlisle, Ailsa J., Bush, Stephen J., Ewing, Adam, Trejo-Reveles, Violeta, Matika, Oswald, de Kloet, Arne, Walsh, Caitlin, Bishop, Stephen C., Prendergast, James G. D., Rainger, Joe, Schoenebeck, Jeffrey J., and Summers, Kim M.
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DOG breeds , *GLAUCOMA - Abstract
Goniodysgenesis is a developmental abnormality of the anterior chamber of the eye. It is generally considered to be congenital in dogs (Canis lupus familiaris), and has been associated with glaucoma and blindness. Goniodysgenesis and early-onset glaucoma initially emerged in Border Collies in Australia in the late 1990s and have subsequently been found in this breed in Europe and the USA. The objective of the present study was to determine the genetic basis of goniodysgenesis in Border Collies. Clinical diagnosis was based on results of examinations by veterinary ophthalmologists of affected and unaffected dogs from eleven different countries. Genotyping using the Illumina high density canine single nucleotide variant genotyping chip was used to identify a candidate genetic region. There was a highly significant peak of association over chromosome 17, with a p-value of 2 · 10213. Expression profiles and evolutionary conservation of candidate genes were assessed using public databases. Whole genome sequences of three dogs with glaucoma, three severely affected by goniodysgenesis and three unaffected dogs identified a missense variant in the olfactomedin like 3 (OLFML3) gene in all six affected animals. This was homozygous for the risk allele in all nine cases with glaucoma and 12 of 14 other severely affected animals. Of 67 reportedly unaffected animals, only one was homozygous for this variant (offspring of parents both with goniodysgenesis who were also homozygous for the variant). Analysis of pedigree information was consistent with an autosomal recessive mode of inheritance for severe goniodysgenesis (potentially leading to glaucoma) in this breed. The identification of a candidate genetic region and putative causative variant will aid breeders to reduce the frequency of goniodysgenesis and the risk of glaucoma in the Border Collie population. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
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