32 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.
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- 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. Meta-analysis of heritability estimates and genome-wide association for tick-borne haemoparasites in African cattle
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Riggio, Valentina, primary, Madder, Maxime, additional, Labuschagne, Michel, additional, Callaby, Rebecca, additional, Zhao, Rongrong, additional, Djikeng, Appolinaire, additional, Fourie, Josephus, additional, Prendergast, James G. D., additional, and Morrison, Liam J., additional
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- 2023
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7. 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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8. Cancer, DNA repair and chromatin structure
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Prendergast, James G. D.
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616.994 - Abstract
In this project we have adopted a number of approaches to try and further characterise the genetic contribution of colorectal cancer. To begin to understand tumour progression we first characterised the gene expression changes observed in various tumours using SAGE, EST and microarray data. Although many genes were identified as differentially expressed in cancers, little congruence was observed between tumour types and even expression platforms. We next compared gene expression changes observed along chromosomes to local chromatin structure, and showed that regions of constitutively open structure generally shown an increase in gene expression in cancer. Despite the lack of congruence between expression data shown previously, we illustrated that such a correlation between gene expression change in tumours and chromatin structure can be observed using various expression platforms and across a variety of tumours. To further characterise the role of chromatin structure in tumours we also investigated the rates of mutation and selection across chromatin categories. DNA damage and repair is a key process in cancer progression and we have shown, through inter species alignments, that although chromosomal regions of a relatively more open chromatin structure undergo lower rates of mutation, levels of purifying selection on synonymous sites are highest in regions of closed chromatin. As part of the COGS/SOCCS group the role of DNA repair in colorectal cancer was finally further investigated through a case-control association study. Tagging SNPs in genes predicted to be associated with DNA repair were selected and subsequently typed by the group in approximately 1000 cases and 1000 controls. The nature of SNPs with evidence of an association with colorectal cancer was finally characterised.
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- 2008
9. 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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10. Rare genetic variants underlie outlying levels of DNA methylation and gene-expression
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Chundru, V Kartik, primary, Marioni, Riccardo E, additional, Prendergast, James G D, additional, Lin, Tian, additional, Beveridge, Allan J, additional, Martin, Nicholas G, additional, Montgomery, Grant W, additional, Hume, David A, additional, Deary, Ian J, additional, Visscher, Peter M, additional, Wray, Naomi R, additional, and McRae, Allan F, additional
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- 2023
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11. A locus conferring tolerance to Theileria infection in African cattle
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Wragg, David, primary, Cook, Elizabeth A. J., additional, Latré de Laté, Perle, additional, Sitt, Tatjana, additional, Hemmink, Johanneke D., additional, Chepkwony, Maurine C., additional, Njeru, Regina, additional, Poole, E. Jane, additional, Powell, Jessica, additional, Paxton, Edith A., additional, Callaby, Rebecca, additional, Talenti, Andrea, additional, Miyunga, Antoinette A., additional, Ndambuki, Gideon, additional, Mwaura, Stephen, additional, Auty, Harriet, additional, Matika, Oswald, additional, Hassan, Musa, additional, Marshall, Karen, additional, Connelley, Timothy, additional, Morrison, Liam J., additional, Bronsvoort, B. Mark deC., additional, Morrison, W. Ivan, additional, Toye, Philip G., additional, and Prendergast, James G. D., additional
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- 2022
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12. Additional file 3 of 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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Additional file 3. Figures S1 to S5 and Tables S1 to S2.
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- 2022
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13. 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, primary, Cook, Elizabeth A. J., additional, Wragg, David, additional, Poole, E. Jane, additional, Ndambuki, Gideon, additional, Miyunga, Antoinette Aluoch, additional, Chepkwony, Maurine C., additional, Mwaura, Stephen, additional, Ndiwa, Nicholas, additional, Prettejohn, Giles, additional, Sitt, Tatjana, additional, Van Aardt, Richard, additional, Morrison, W. Ivan, additional, Prendergast, James G. D., additional, and Toye, Philip, additional
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- 2021
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14. Clinical Evaluation of Corridor Disease in Bos indicus (Boran) Cattle Naturally Infected With Buffalo-Derived Theileria parva
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Cook, Elizabeth A. J., primary, Sitt, Tatjana, additional, Poole, E. Jane, additional, Ndambuki, Gideon, additional, Mwaura, Stephen, additional, Chepkwony, Maurine C., additional, Latre de Late, Perle, additional, Miyunga, Antoinette A., additional, van Aardt, Richard, additional, Prettejohn, Giles, additional, Wragg, David, additional, Prendergast, James G. D., additional, Morrison, W. Ivan, additional, and Toye, Philip, additional
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- 2021
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15. 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, Lin, Tian, Berveridge, Allan J, Consortium, Sgpd, Gratten, Jacob, Hume, David A, Deary, Ian J, Wray, Naomi R, Visscher, Peter M, and McRae, Allan F
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Linkage disequilibrium ,Quantitative Trait Loci ,Bayesian probability ,imputation ,Investigations ,Quantitative trait locus ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Quantitative Trait, Heritable ,Genetics ,Humans ,1000 Genomes Project ,Allele ,Association mapping ,030304 developmental biology ,0303 health sciences ,Whole Genome Sequencing ,030305 genetics & heredity ,Haplotype ,Reproducibility of Results ,DNA Methylation ,Reference Standards ,fine-mapping ,CpG-SNPs ,CpG Islands ,DNA-methylation ,Statistical Genetics and Genomics ,Imputation (genetics) ,Genome-Wide Association Study - Abstract
This study highlights dangers in over-interpreting fine-mapping results. Chundru et al. show that genotype imputation accuracy has a large impact on fine-mapping accuracy. They used DNA methylation at CpG-sites with a variant..., 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.
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- 2019
16. Arginine to Glutamine Variant in Olfactomedin Like 3 (OLFML3) Is a Candidate for Severe Goniodysgenesis and Glaucoma in the Border Collie Dog Breed
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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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Male ,genetic structures ,olfactomedin like 3 ,Anterior Chamber ,Mutation, Missense ,canine ,Chick Embryo ,QH426-470 ,Investigations ,Polymorphism, Single Nucleotide ,Mice ,Dogs ,Border Collie ,Genetics ,GWAS ,Animals ,Humans ,Amino Acid Sequence ,Dog Diseases ,Eye Proteins ,Glycoproteins ,whole genome sequencing ,Extracellular Matrix Proteins ,Glaucoma ,Sequence Analysis, DNA ,goniodysgenesis ,Gene Expression Regulation ,eye development ,Female ,Goniodysgenesis ,Sequence Alignment ,Genome-Wide Association Study - 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 × 10−13. 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.
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- 2019
17. 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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18. Whole-Genome Sequence Data Suggest Environmental Adaptation of Ethiopian Sheep Populations
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Wiener, Pamela, primary, Robert, Christelle, additional, Ahbara, Abulgasim, additional, Salavati, Mazdak, additional, Abebe, Ayele, additional, Kebede, Adebabay, additional, Wragg, David, additional, Friedrich, Juliane, additional, Vasoya, Deepali, additional, Hume, David A, additional, Djikeng, Appolinaire, additional, Watson, Mick, additional, Prendergast, James G D, additional, Hanotte, Olivier, additional, Mwacharo, Joram M, additional, and Clark, Emily L, additional
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- 2021
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19. Species-Specificity of Transcriptional Regulation and the Response to Lipopolysaccharide in Mammalian Macrophages
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Bush, Stephen J., primary, McCulloch, Mary E. B., additional, Lisowski, Zofia M., additional, Muriuki, Charity, additional, Clark, Emily L., additional, Young, Rachel, additional, Pridans, Clare, additional, Prendergast, James G. D., additional, Summers, Kim M., additional, and Hume, David A., additional
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- 2020
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20. 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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21. Linked Mutations at Adjacent Nucleotides Have Shaped Human Population Differentiation and Protein Evolution
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Prendergast, James G D, primary, Pugh, Carys, additional, Harris, Sarah E, additional, Hume, David A, additional, Deary, Ian J, additional, and Beveridge, Allan, additional
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- 2019
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22. The Constrained Maximal Expression Level Owing to Haploidy Shapes Gene Content on the Mammalian X Chromosome
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Hurst, Laurence D., Ghanbarian, Avazeh T., Forrest, Alistair R R, Huminiecki, Lukasz, 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, Baker, Sarah, Balwierz, Piotr J., Beckhouse, Anthony G., Pradhan, Swati Bhatt, 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, 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, Iida, Kei, Ikawa, Tomokatsu, Jankovic, Boris R., Jia, Hui, Joshi, Anagha, Jurman, Giuseppe, Kaczkowski, Bogumil, Kai, Chieko, Kaida, Kaoru, Kaiho, Ai, Kajiyama, Kazuhiro, Kanamori, Mutsumi Katayama, 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, Alan sim, Manabe, Riichiroh, 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, Sayaka Sato, 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, Mariko Hatakeyama, 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, Suzan 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 Gustav, Hume, David A., Carninci, Piero, Hayashizaki, Yoshihide, Hubrecht Institute for Developmental Biology and Stem Cell Research, Barton, Nick H, Amsterdam institute for Infection and Immunity, Infectious diseases, and Experimental Immunology
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Male ,Medical and Health Sciences ,Essential ,Models ,Gene expression ,Databases, Genetic ,Biology (General) ,Non-U.S. Gov't ,X-linked recessive inheritance ,X chromosome ,Cells, Cultured ,Regulation of gene expression ,Genetics ,Sex Characteristics ,Dosage compensation ,Tumor ,Cultured ,Genes, Essential ,Genome ,Agricultural and Biological Sciences(all) ,General Neuroscience ,Research Support, Non-U.S. Gov't ,Biological Sciences ,Organ Specificity ,Female ,General Agricultural and Biological Sciences ,Research Article ,Human ,X Chromosome ,Retroelements ,QH301-705.5 ,Neuroscience(all) ,1.1 Normal biological development and functioning ,Cells ,Down-Regulation ,Biology ,Research Support ,General Biochemistry, Genetics and Molecular Biology ,Chromosomes ,Cell Line ,Databases ,Genetic ,Species Specificity ,Underpinning research ,Immunology and Microbiology(all) ,Cell Line, Tumor ,Journal Article ,Animals ,Humans ,Comparative Study ,Gene ,Chromosomes, Human, X ,Autosome ,General Immunology and Microbiology ,Agricultural and Veterinary Sciences ,Models, Genetic ,Biochemistry, Genetics and Molecular Biology(all) ,Genome, Human ,Mammalian ,Human Genome ,Chromosomes, Mammalian ,Genes ,Gene Expression Regulation ,Human genome ,FANTOM consortium ,Developmental Biology - Abstract
X chromosomes are unusual in many regards, not least of which is their nonrandom gene content. The causes of this bias are commonly discussed in the context of sexual antagonism and the avoidance of activity in the male germline. Here, we examine the notion that, at least in some taxa, functionally biased gene content may more profoundly be shaped by limits imposed on gene expression owing to haploid expression of the X chromosome. Notably, if the X, as in primates, is transcribed at rates comparable to the ancestral rate (per promoter) prior to the X chromosome formation, then the X is not a tolerable environment for genes with very high maximal net levels of expression, owing to transcriptional traffic jams. We test this hypothesis using The Encyclopedia of DNA Elements (ENCODE) and data from the Functional Annotation of the Mammalian Genome (FANTOM5) project. As predicted, the maximal expression of human X-linked genes is much lower than that of genes on autosomes: on average, maximal expression is three times lower on the X chromosome than on autosomes. Similarly, autosome-to-X retroposition events are associated with lower maximal expression of retrogenes on the X than seen for X-to-autosome retrogenes on autosomes. Also as expected, X-linked genes have a lesser degree of increase in gene expression than autosomal ones (compared to the human/Chimpanzee common ancestor) if highly expressed, but not if lowly expressed. The traffic jam model also explains the known lower breadth of expression for genes on the X (and the Z of birds), as genes with broad expression are, on average, those with high maximal expression. As then further predicted, highly expressed tissue-specific genes are also rare on the X and broadly expressed genes on the X tend to be lowly expressed, both indicating that the trend is shaped by the maximal expression level not the breadth of expression per se. Importantly, a limit to the maximal expression level explains biased tissue of expression profiles of X-linked genes. Tissues whose tissue-specific genes are very highly expressed (e.g., secretory tissues, tissues abundant in structural proteins) are also tissues in which gene expression is relatively rare on the X chromosome. These trends cannot be fully accounted for in terms of alternative models of biased expression. In conclusion, the notion that it is hard for genes on the Therian X to be highly expressed, owing to transcriptional traffic jams, provides a simple yet robustly supported rationale of many peculiar features of X’s gene content, gene expression, and evolution., Laurence Hurst, Lukasz Huminiecki, and the FANTOM5 consortium propose a new explanation for the peculiar expression properties of genes on the human X chromosome, based on the premise that very high expression levels cannot be achieved on a haploid-expressed chromosome., Author Summary Genes located on the human X chromosome are not a random mix of genes: they tend to be expressed in relatively few tissues or are specific for a particular set of tissues, e.g., brain regions. Prior attempts to explain this skewed gene content have hypothesized that the X chromosome might be peculiar because it has to balance mutations that are advantageous to one sex but deleterious to the other, or because it has to shut down during the process of sperm manufacture in males. Here we suggest and test a third possible explanation: that genes on the X chromosome are limited in their transcription levels and thus tend to be genes that are lowly or specifically expressed. We consider the suggestion that since these genes can only be expressed from one chromosome, as males only have one X, the ability to express a gene at very high rates is limited owing to potential transcriptional traffic jams. As predicted, we find that human X-located genes have maximal expression rates far below that of genes residing on autosomes. When we look at genes that have moved onto or off the X chromosome during recent evolution, we find the maximal expression is higher when not on the X chromosome. We also find that X-located genes that are relatively highly expressed are not able to increase their expression level further. Our model explains both the enrichment for tissue specificity and the paucity of certain tissues with X-located genes. Genes underrepresented on the X are either expressed in many tissues—such genes tend to have high maximal expression—or are from tissues that require a lot of transcription (e.g., fast secreting tissues like the liver). Just as many of the findings cannot be explained by the two earlier models, neither can the traffic jam model explain all the peculiar features of the genes found on the X chromosome. Indeed, we find evidence of a reproduction-related bias in X-located genes, even after allowing for the traffic jam problem.
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- 2015
23. Shared regulatory sites are abundant in the human genome and shed light on genome evolution and disease pleiotropy
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Tong, Pin, primary, Monahan, Jack, additional, and Prendergast, James G. D., additional
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- 2017
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24. Side Effects: Substantial Non-Neutral Evolution Flanking Regulatory Sites
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Prendergast, James G. D., primary and Semple, Colin A., additional
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- 2013
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25. Sequencing Illustrates the Transcriptional Response of Legionella pneumophila during Infection and Identifies Seventy Novel Small Non-Coding RNAs
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Weissenmayer, Barbara A., primary, Prendergast, James G. D., additional, Lohan, Amanda J., additional, and Loftus, Brendan J., additional
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- 2011
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26. 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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27. hapbin: An Efficient Program for Performing Haplotype-Based Scans for Positive Selection in Large Genomic Datasets.
- Author
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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]
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- 2015
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28. Chromatin structure and evolution in the human genome.
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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]
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- 2007
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29. 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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30. Genomic Reference Resource for African Cattle: Genome Sequences and High-Density Array Variants.
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Tijjani A, Kambal S, Terefe E, Njeru R, Ogugo M, Ndambuki G, Missohou A, Traore A, Salim B, Ezeasor C, D'andre H C, Obishakin ET, Diallo B, Talaki E, Abdoukarim IY, Nash O, Osei-Amponsah R, Ravaorimanana S, Issa Y, Zegeye T, Mukasa C, Tiambo C, Prendergast JGD, Kemp SJ, Han J, Marshall K, and Hanotte O
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- Cattle genetics, Animals, Genomics, Africa, Breeding, Genetic Variation, Genome
- Abstract
The diversity in genome resources is fundamental to designing genomic strategies for local breed improvement and utilisation. These resources also support gene discovery and enhance our understanding of the mechanisms of resilience with applications beyond local breeds. Here, we report the genome sequences of 555 cattle (208 of which comprise new data) and high-density (HD) array genotyping of 1,082 samples (537 new samples) from indigenous African cattle populations. The new sequences have an average genome coverage of ~30X, three times higher than the average (~10X) of the over 300 sequences already in the public domain. Following variant quality checks, we identified approximately 32.3 million sequence variants and 661,943 HD autosomal variants mapped to the Bos taurus reference genome (ARS-UCD1.2). The new datasets were generated as part of the Centre for Tropical Livestock Genetics and Health (CTLGH) Genomic Reference Resource for African Cattle (GRRFAC) initiative, which aspires to facilitate the generation of this livestock resource and hopes for its utilisation for complete indigenous breed characterisation and sustainable global livestock improvement., (© 2024. The Author(s).)
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- 2024
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31. Sequence-level mechanisms of human epigenome evolution.
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Prendergast JG, Chambers EV, and Semple CA
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- Alu Elements genetics, Amino Acid Motifs, Cell Lineage, DNA Methylation, Gene Expression Regulation, Humans, Chromatin genetics, Epigenomics, Evolution, Molecular
- Abstract
DNA methylation and chromatin states play key roles in development and disease. However, the extent of recent evolutionary divergence in the human epigenome and the influential factors that have shaped it are poorly understood. To determine the links between genome sequence and human epigenome evolution, we examined the divergence of DNA methylation and chromatin states following segmental duplication events in the human lineage. Chromatin and DNA methylation states were found to have been generally well conserved following a duplication event, with the evolution of the epigenome largely uncoupled from the total number of genetic changes in the surrounding DNA sequence. However, the epigenome at tissue-specific, distal regulatory regions was observed to be unusually prone to diverge following duplication, with particular sequence differences, altering known sequence motifs, found to be associated with divergence in patterns of DNA methylation and chromatin. Alu elements were found to have played a particularly prominent role in shaping human epigenome evolution, and we show that human-specific AluY insertion events are strongly linked to the evolution of the DNA methylation landscape and gene expression levels, including at key neurological genes in the human brain. Studying paralogous regions within the same sample enables the study of the links between genome and epigenome evolution while controlling for biological and technical variation. We show DNA methylation and chromatin divergence between duplicated regions are linked to the divergence of particular genetic motifs, with Alu elements having played a disproportionate role in the evolution of the epigenome in the human lineage., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)
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- 2014
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32. Sequencing and analysis of an Irish human genome.
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Tong P, Prendergast JG, Lohan AJ, Farrington SM, Cronin S, Friel N, Bradley DG, Hardiman O, Evans A, Wilson JF, and Loftus B
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- Base Sequence, Chromosome Mapping, Codon, Nonsense, Gene Duplication, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Geography, Haplotypes, Human Genome Project, Humans, INDEL Mutation, Inflammatory Bowel Diseases genetics, Ireland, Male, Polymorphism, Single Nucleotide, Selection, Genetic, Genome, Human, Sequence Analysis, DNA, White People genetics
- Abstract
Background: Recent studies generating complete human sequences from Asian, African and European subgroups have revealed population-specific variation and disease susceptibility loci. Here, choosing a DNA sample from a population of interest due to its relative geographical isolation and genetic impact on further populations, we extend the above studies through the generation of 11-fold coverage of the first Irish human genome sequence., Results: Using sequence data from a branch of the European ancestral tree as yet unsequenced, we identify variants that may be specific to this population. Through comparisons with HapMap and previous genetic association studies, we identified novel disease-associated variants, including a novel nonsense variant putatively associated with inflammatory bowel disease. We describe a novel method for improving SNP calling accuracy at low genome coverage using haplotype information. This analysis has implications for future re-sequencing studies and validates the imputation of Irish haplotypes using data from the current Human Genome Diversity Cell Line Panel (HGDP-CEPH). Finally, we identify gene duplication events as constituting significant targets of recent positive selection in the human lineage., Conclusions: Our findings show that there remains utility in generating whole genome sequences to illustrate both general principles and reveal specific instances of human biology. With increasing access to low cost sequencing we would predict that even armed with the resources of a small research group a number of similar initiatives geared towards answering specific biological questions will emerge.
- Published
- 2010
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- View/download PDF
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