26 results on '"Prendergast, James G D"'
Search Results
2. 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
- Full Text
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3. 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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4. 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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5. 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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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. High performance imputation of structural and single nucleotide variants in Atlantic salmon using low-coverage whole genome sequencing
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Gundappa, Manu Kumar, primary, Robledo, Diego, additional, Hamilton, Alastair, additional, Houston, Ross D., additional, Prendergast, James G. D., additional, and Macqueen, Daniel J., additional
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- 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, 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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10. 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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11. 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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12. 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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13. 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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14. 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
15. 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
16. 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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17. 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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18. 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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19. 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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- 2018
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20. 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.
- Published
- 2015
21. 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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22. 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]
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- 2015
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23. 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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24. Continent-wide genomic analysis of the African buffalo (Syncerus caffer).
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Talenti A, Wilkinson T, Cook EA, Hemmink JD, Paxton E, Mutinda M, Ngulu SD, Jayaraman S, Bishop RP, Obara I, Hourlier T, Garcia Giron C, Martin FJ, Labuschagne M, Atimnedi P, Nanteza A, Keyyu JD, Mramba F, Caron A, Cornelis D, Chardonnet P, Fyumagwa R, Lembo T, Auty HK, Michaux J, Smitz N, Toye P, Robert C, Prendergast JGD, and Morrison LJ
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- Animals, Gene Flow, Africa South of the Sahara, Genetics, Population, Phylogeny, Genetic Variation, Buffaloes genetics, Genomics methods, Genome
- Abstract
The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided little support for the currently described four subspecies. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management., (© 2024. The Author(s).)
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- 2024
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25. Rare Missense Functional Variants at COL4A1 and COL4A2 in Sporadic Intracerebral Hemorrhage.
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Chung J, Hamilton G, Kim M, Marini S, Montgomery B, Henry J, Cho AE, Brown DL, Worrall BB, Meschia JF, Silliman SL, Selim M, Tirschwell DL, Kidwell CS, Kissela B, Greenberg SM, Viswanathan A, Goldstein JN, Langefeld CD, Rannikmae K, Sudlow CLM, Samarasekera N, Rodrigues M, Al-Shahi Salman R, Prendergast JGD, Harris SE, Deary I, Woo D, Rosand J, Van Agtmael T, and Anderson CD
- Abstract
Objective: To test the genetic contribution of rare missense variants in COL4A1 and COL4A2 in which common variants are genetically associated with sporadic intracerebral hemorrhage (ICH), we performed rare variant analysis in multiple sequencing data for the risk for sporadic ICH., Methods: We performed sequencing across 559 Kbp at 13q34 including COL4A1 and COL4A2 among 2,133 individuals (1,055 ICH cases; 1,078 controls) in United States-based and 1,381 individuals (192 ICH cases; 1,189 controls) from Scotland-based cohorts, followed by sequence annotation, functional impact prediction, genetic association testing, and in silico thermodynamic modeling., Results: We identified 107 rare nonsynonymous variants in sporadic ICH, of which 2 missense variants, rs138269346 (COL4A1
I110T ) and rs201716258 (COL4A2H203L ), were predicted to be highly functional and occurred in multiple ICH cases but not in controls from the United States-based cohort. The minor allele of rs201716258 was also present in Scottish patients with ICH, and rs138269346 was observed in 2 ICH-free controls with a history of hypertension and myocardial infarction. Rs138269346 was nominally associated with nonlobar ICH risk ( p = 0.05), but not with lobar ICH ( p = 0.08), while associations between rs201716258 and ICH subtypes were nonsignificant ( p > 0.12). Both variants were considered pathogenic based on minor allele frequency (<0.00035 in European populations), predicted functional impact (deleterious or probably damaging), and in silico modeling studies (substantially altered physical length and thermal stability of collagen)., Conclusions: We identified rare missense variants in COL4A1 / A2 in association with sporadic ICH. Our annotation and simulation studies suggest that these variants are highly functional and may represent targets for translational follow-up., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)- Published
- 2021
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26. Exome sequencing to detect rare variants associated with general cognitive ability: a pilot study.
- Author
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Luciano M, Svinti V, Campbell A, Marioni RE, Hayward C, Wright AF, Taylor MS, Porteous DJ, Thomson P, Prendergast JG, Hastie ND, Farrington SM, Scotland G, Dunlop MG, and Deary IJ
- Subjects
- Adult, Aged, Female, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Pilot Projects, Scotland, Cognition, Exome, Intelligence genetics, Quantitative Trait Loci
- Abstract
Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.
- Published
- 2015
- Full Text
- View/download PDF
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