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Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

التفاصيل البيبلوغرافية
العنوان: Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage
المؤلفون: Chen, Zhongbo, Zhang, David, Reynolds, Regina H., Gustavsson, Emil K., García-Ruiz, Sonia, D'Sa, Karishma, Fairbrother-Browne, Aine, Vandrovcova, Jana, Noyce, Alastair J., Kaiyrzhanov, Rauan, Middlehurst, Ben, Kia, Demis A., Tan, Manuela, Morris, Huw R., Plun-Favreau, Helen, Holmans, Peter, Trabzuni, Daniah, Bras, Jose, Quinn, John, Mok, Kin Y., Kinghorn, Kerri J., Billingsley, Kimberley, Wood, Nicholas W., Lewis, Patrick, Schreglmann, Sebastian, Guerreiro, Rita, Lovering, Ruth, R'Bibo, Lea, Manzoni, Claudia, Rizig, Mie, Guelfi, Sebastian, Escott-Price, Valentina, Chelban, Viorica, Foltynie, Thomas, Williams, Nigel, Brice, Alexis, Danjou, Fabrice, Lesage, Suzanne, Corvol, Jean-Christophe, Martinez Rande, Maria, Schulte, Claudia, Brockmann, Kathrin, Simón-Sánchez, Javier, Heutink, Peter, Rizzu, Patrizia, Sharma, Manu, Gasser, Thomas, Nicolas, Aude, Cookson, Mark R, Bandres-Ciga, Sara, Blauwendraat, Cornelis, Craig, David W, Faghri, Faraz, Gibbs, J.Raphael, Hernandez, Dena G., Van Keuren-Jensen, Kendall, Shulman, Joshua M., Leonard, Hampton L., Nalls, Mike A., Robak, Laurie, Lubbe, Steven, Finkbeiner, Steven, Mencacci, Niccolo E., Lungu, Codrin, Singleton, Andrew B., Scholz, Sonja W., Reed, Xylena, Alcalay, Roy N, Gan-Or, Ziv, Rouleau, Guy A., Krohn, Lynne, van Hilten, Jacobus J., Marinus, Johan, Adarmes-Gómez, A.D, Aguilar Barberà , Miquel, Alvarez, Ignacio, Alvarez, Victoria, Barrero, Francisco Javier, Bergareche Yarza, Jesús Alberto, Bernal-Bernal, Inmaculada, Blázquez Estrada, Marta, Bonilla-Toribio, Marta, Botía, Juan, Boungiorno, M. T, Buiza-Rueda, Dolores, Cámara, Ana, Carrillo, Fátima, Carrión-Claro, M, Cerdan, Debora, Clarimón, Jordi, Compta, Yaroslau, Diez-Fairen, Monica, Dols Icardo, Oriol, Duarte, Jacinto, Duran, Raquel, Escamilla-Sevilla, Francisco, Ezquerra, Mario, Feliz, Cici, Fernández, Manel, Fernández-Santiago, Rubén, Garcia, Ciara, García-Ruiz, Pedro, Gómez-Garre, Pilar, Gomez Heredia, Maria Jose, Gonzalez-Aramburu, Isabel, Gorostidi Pagola, Ana, Hoenicka, Janet, Infante, Jon, Jesús, Silvia, Jimenez-Escrig, Adriano, Kulisevsky, Jaime, Labrador-Espinosa, Miguel A, Lopez-Sendon, Jose Luis, López de Munain Arregui, Adolfo, Macias, Daniel, Martínez Torres, Irene, Marín, Juan, Marti, Maria Jose, Martínez-Castrillo, Juan Carlos, Méndez-del-Barrio, Carlota, Menéndez González, Manuel, Mata, Marina, Mínguez, Adolfo, Mir, Pablo, Mondragon Rezola, Elisabet, Muñoz, Esteban, Pagonabarraga Mora, Javier, Pastor, Pau, Perez Errazquin, Francisco, Periñán-Tocino, Teresa, Ruiz-Martínez, Javier, Ruz, Clara, Sanchez Rodriguez, Antonio, Sierra, María, Suarez-Sanmartin, Esther, Tabernero, Cesar, Tartari, Juan Pablo, Tejera-Parrado, Cristina, Tolosa, Eduard, Valldeoriola, Francesc, Vargas-González, Laura, Vela, Lydia, Vives, Francisco, Zimprich, Alexander, Pihlstrom, Lasse, Toft, Mathias, Koks, Sulev, Taba, Pille, Hassin-Baer, Sharon, Hardy, John, Houlden, Henry, Gagliano Taliun, Sarah A., Ryten, Mina, Universitat Autònoma de Barcelona
سنة النشر: 2021
المجموعة: Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB
مصطلحات موضوعية: Alzheimer Disease, Apolipoproteins E, Brain, Chromosomes, Human, Pair 19, Conserved Sequence, DNA, Intergenic, Gene Ontology, Genome, Humans, Introns, Linkage Disequilibrium, Molecular Sequence Annotation, Neurodegenerative Diseases, Phenotype, Phylogeny, Polymorphism, Single Nucleotide, Regression Analysis, RNA, Long Noncoding, Messenger
الوصف: Altres ajuts: Leonard Wolfson Foundation; United Kingdom Medical Research Council (MRC, MR/N008324/1); DRI Limited; UK Medical Research Council; Alzheimer's Society and Alzheimer's Research UK; Medical Research Council (MR/N026004/1); Wellcome Trust (202903/Z/16/Z); Dolby Family Fund; National Institute for Health Research; University College London; Fundación Séneca, Agencia de Ciencia y Tecnología de la Región de Murcia (00007/COVI/20). ; Knowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer's disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 20411723
4487-4138
العلاقة: Nature communications; Vol. 12 Núm. 1 (january 2021), p. 2076; https://ddd.uab.cat/record/272005Test; urn:10.1038/s41467-021-22262-5; urn:oai:ddd.uab.cat:272005; urn:scopus_id:85104099832; urn:articleid:20411723v12n1p2076; urn:pmid:33824317; urn:pmc-uid:8024253; urn:pmcid:PMC8024253; urn:oai:pubmedcentral.nih.gov:8024253; urn:oai:egreta.uab.cat:publications/c5981b2e-4487-4138-93ee-bac8e1b1beb4
الإتاحة: https://ddd.uab.cat/record/272005Test
حقوق: open access ; Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. ; https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.A8F739ED
قاعدة البيانات: BASE
الوصف
تدمد:20411723
44874138