التفاصيل البيبلوغرافية
العنوان:
Identification of sixteen novel candidate genes for late onset Parkinson's disease
المؤلفون:
Gialluisi, Alessandro , Reccia, Mafalda Giovanna , Modugno, Nicola , Nutile, Teresa , Lombardi, Alessia , Di Giovannantonio, Luca Giovanni , Pietracupa, Sara , Ruggiero, Daniela , Scala, Simona , Gambardella, Stefano , Noyce, Alastair J. , Kaiyrzhanov, Rauan , Middlehurst, Ben , Kia, Demis A. , Tan, Manuela , Houlden, Henry , Morris, Huw R. , Plun-Favreau, Helen , Holmans, Peter , Hardy, John , Trabzuni, Daniah , Quinn, John , Bubb, Vivien , Mok, Kin Y. , Kinghorn, Kerri J. , Billingsley, Kimberley , Wood, Nicholas W. , Lewis, Patrick , Schreglmann, Sebastian , Lovering, Rruth , R'Bibo, Lea , Manzoni, Claudia , Rizig, Mie , Ryten, Mina , Guelfi, Sebastian , Escott-Price, Valentina , Chelban, Viorica , Foltynie, Thomas , Williams, Nigel , Morrison, Karen E. , Clarke, Carl , Brice, Alexis , Danjou, Fabrice , Lesage, Suzanne , Corvol, Jean-Christophe , Martinez, Maria , Schulte, Claudia , Brockmann, Kathrin , Simón-Sánchez, Javier , Heutink, Peter , Rizzu, Patrizia , Sharma, Manu , Gasser, Thomas , Cookson, Mark R. , Bandres-Ciga, Sara , Blauwendraat, Cornelis , Craig, David W. , Narendra, Derek , Faghri, Faraz , Gibbs, J.Raphael , Hernandez, Dena G. , Van Keuren-Jensen, Kendall , Shulman, Joshua M. , Iwaki, Hirotaka , Leonard, Hampton L. , Nalls, Mike A. , Robak, Laurie , Bras, Jose , Guerreiro, Rita , Lubbe, Steven , Finkbeiner, Steven , Mencacci, Niccolo E. , Lungu, Codrin , Singleton, Andrew B. , Scholz, Sonja W. , Reed, Xylena , Alcalay, Roy N. , Gan-Or, Zin , 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 , Blazquez, Marta , Bonilla-Toribio, Marta , Botía, Juan A. , Boungiorno, María Teresa , Buiza-Rueda, Dolores , 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 , Majamaa, Kari , Siitonen, Ari , Okubadejo, Njideka U. , Ojo, Oluwadamilola O. , Shashkin, Chingiz , Zharkynbekova, Nazira , Akhmetzhanov, Vadim , Aitkulova, Akbota , Zholdybayeva, Elena , Zharmukhanov, Zharkyn , Kaishybayeva, Gulnaz , Karimova, Altynay , Sadykova, Dinara , Iacoviello, Licia , Gianfrancesco, F. , Acampora, D. , D'Esposito, M. , Simeone, A. , Ciullo, M. , Esposito, T.
المساهمون:
Universidad de Cantabria
المصدر:
Molecular neurodegeneration 16, 35 (2021)https://doi.org/10.1186/s13024-021-00455-2Test
بيانات النشر:
BioMed Central, 2021.
سنة النشر:
2021
مصطلحات موضوعية:
0301 basic medicine , Male , Aging , Candidate gene , Parkinson's disease , Neurodegenerative , Bioinformatics , 0302 clinical medicine , Late onset Parkinson’s disease , Novel candidate genes for Parkinson’s disease , Rare variant burden analysis , Whole exome sequencing , Adult , Age of Onset , Aged , Female , Genetic Predisposition to Disease , Humans , Middle Aged , Parkinson Disease , Pedigree , Whole Exome Sequencing , 2.1 Biological and endogenous factors , Medicine , Novel candidate genes for Parkinson's disease , Aetiology , Exome , Exome sequencing , screening and diagnosis , education.field_of_study , Parkinson's Disease , LRRK2 , International Parkinson’s Disease Genomics Consortium , Detection , Neurological , Late onset Parkinson's disease , 4.2 Evaluation of markers and technologies , Research Article , Clinical Sciences , Population , 03 medical and health sciences , Cellular and Molecular Neuroscience , Clinical Research , Exome Sequencing , Genetics , RC346-429 , education , Molecular Biology , Neurology & Neurosurgery , business.industry , Genetic heterogeneity , Prevention , RC952-954.6 , Neurosciences , PARK7 , medicine.disease , Brain Disorders , 030104 developmental biology , Geriatrics , Neurology. Diseases of the nervous system , Neurology (clinical) , business , 030217 neurology & neurosurgery
الوصف:
Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis of PD. Methods The study includes a discovery stage based on the analysis of whole exome data from 26 dominant late onset PD families, a validation analysis performed on 1542 independent PD patients and 706 controls from different cohorts and the assessment of polygenic variants load in the Italian cohort (394 unrelated patients and 203 controls). Results Family-based approach identified 28 disrupting variants in 26 candidate genes for PD including PARK2, PINK1, DJ-1(PARK7), LRRK2, HTRA2, FBXO7, EIF4G1, DNAJC6, DNAJC13, SNCAIP, AIMP2, CHMP1A, GIPC1, HMOX2, HSPA8, IMMT, KIF21B, KIF24, MAN2C1, RHOT2, SLC25A39, SPTBN1, TMEM175, TOMM22, TVP23A and ZSCAN21. Sixteen of them have not been associated to PD before, were expressed in mesencephalon and were involved in pathways potentially deregulated in PD. Mutation analysis in independent cohorts disclosed a significant excess of highly deleterious variants in cases (p = 0.0001), supporting their role in PD. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in the 26 genes may predict PD occurrence in about 20% of patients, both familial and sporadic cases, with high specificity (> 93%; p = 4.4 × 10− 5). Moreover, our data highlight the fact that the genetic landmarks of late onset PD does not systematically differ between sporadic and familial forms, especially in the case of small nuclear families and underline the importance of rare variants in the genetics of sporadic PD. Furthermore, patients carrying multiple rare variants showed higher risk of manifesting dyskinesia induced by levodopa treatment. Conclusions Besides confirming the extreme genetic heterogeneity of PD, these data provide novel insights into the genetic of the disease and may be relevant for its prediction, diagnosis and treatment.
وصف الملف:
application/pdf
الوصول الحر:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7c06eb493f63a6ca32b1a3e8f8714119Test http://hdl.handle.net/10902/24037Test
حقوق:
OPEN
رقم الانضمام:
edsair.doi.dedup.....7c06eb493f63a6ca32b1a3e8f8714119
قاعدة البيانات:
OpenAIRE
