ALBERT

Description: Birds are the most species-rich class of tetrapod vertebrates and have wide relevance across many research fields. We explored bird macroevolution using full genomes from 48 avian species representing all major extant clades. The avian genome is principally characterized by its constrained size, which predominantly arose because of lineage-specific erosion of repetitive elements, large segmental deletions, and gene loss. Avian genomes furthermore show a remarkably high degree of evolutionary stasis at the levels of nucleotide sequence, gene synteny, and chromosomal structure. Despite this pattern of conservation, we detected many non-neutral evolutionary changes in protein-coding genes and noncoding regions. These analyses reveal that pan-avian genomic diversity covaries with adaptations to different lifestyles and convergent evolution of traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390078/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390078/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Guojie -- Li, Cai -- Li, Qiye -- Li, Bo -- Larkin, Denis M -- Lee, Chul -- Storz, Jay F -- Antunes, Agostinho -- Greenwold, Matthew J -- Meredith, Robert W -- Odeen, Anders -- Cui, Jie -- Zhou, Qi -- Xu, Luohao -- Pan, Hailin -- Wang, Zongji -- Jin, Lijun -- Zhang, Pei -- Hu, Haofu -- Yang, Wei -- Hu, Jiang -- Xiao, Jin -- Yang, Zhikai -- Liu, Yang -- Xie, Qiaolin -- Yu, Hao -- Lian, Jinmin -- Wen, Ping -- Zhang, Fang -- Li, Hui -- Zeng, Yongli -- Xiong, Zijun -- Liu, Shiping -- Zhou, Long -- Huang, Zhiyong -- An, Na -- Wang, Jie -- Zheng, Qiumei -- Xiong, Yingqi -- Wang, Guangbiao -- Wang, Bo -- Wang, Jingjing -- Fan, Yu -- da Fonseca, Rute R -- Alfaro-Nunez, Alonzo -- Schubert, Mikkel -- Orlando, Ludovic -- Mourier, Tobias -- Howard, Jason T -- Ganapathy, Ganeshkumar -- Pfenning, Andreas -- Whitney, Osceola -- Rivas, Miriam V -- Hara, Erina -- Smith, Julia -- Farre, Marta -- Narayan, Jitendra -- Slavov, Gancho -- Romanov, Michael N -- Borges, Rui -- Machado, Joao Paulo -- Khan, Imran -- Springer, Mark S -- Gatesy, John -- Hoffmann, Federico G -- Opazo, Juan C -- Hastad, Olle -- Sawyer, Roger H -- Kim, Heebal -- Kim, Kyu-Won -- Kim, Hyeon Jeong -- Cho, Seoae -- Li, Ning -- Huang, Yinhua -- Bruford, Michael W -- Zhan, Xiangjiang -- Dixon, Andrew -- Bertelsen, Mads F -- Derryberry, Elizabeth -- Warren, Wesley -- Wilson, Richard K -- Li, Shengbin -- Ray, David A -- Green, Richard E -- O'Brien, Stephen J -- Griffin, Darren -- Johnson, Warren E -- Haussler, David -- Ryder, Oliver A -- Willerslev, Eske -- Graves, Gary R -- Alstrom, Per -- Fjeldsa, Jon -- Mindell, David P -- Edwards, Scott V -- Braun, Edward L -- Rahbek, Carsten -- Burt, David W -- Houde, Peter -- Zhang, Yong -- Yang, Huanming -- Wang, Jian -- Avian Genome Consortium -- Jarvis, Erich D -- Gilbert, M Thomas P -- Wang, Jun -- DP1 OD000448/OD/NIH HHS/ -- DP1OD000448/OD/NIH HHS/ -- R01 HL087216/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1311-20. doi: 10.1126/science.1251385. Epub 2014 Dec 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. Centre for Social Evolution, Department of Biology, Universitetsparken 15, University of Copenhagen, DK-2100 Copenhagen, Denmark. zhanggj@genomics.cn jarvis@neuro.duke.edu mtpgilbert@gmail.com wangj@genomics.cn. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. ; Royal Veterinary College, University of London, London, UK. ; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Republic of Korea. Cho and Kim Genomics, Seoul National University Research Park, Seoul 151-919, Republic of Korea. ; School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA. ; Centro de Investigacion en Ciencias del Mar y Limnologia (CIMAR)/Centro Interdisciplinar de Investigacao Marinha e Ambiental (CIIMAR), Universidade do Porto, Rua dos Bragas, 177, 4050-123 Porto, Portugal. Departamento de Biologia, Faculdade de Ciencias, Universidade do Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal. ; Department of Biological Sciences, University of South Carolina, Columbia, SC, USA. ; Department of Biology and Molecular Biology, Montclair State University, Montclair, NJ 07043, USA. ; Department of Animal Ecology, Uppsala University, Norbyvagen 18D, S-752 36 Uppsala, Sweden. ; Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857, Singapore. ; Department of Integrative Biology University of California, Berkeley, CA 94720, USA. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. College of Life Sciences, Wuhan University, Wuhan 430072, China. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. BGI Education Center,University of Chinese Academy of Sciences,Shenzhen, 518083, China. ; Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. ; Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. ; Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, UK. ; School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK. ; Centro de Investigacion en Ciencias del Mar y Limnologia (CIMAR)/Centro Interdisciplinar de Investigacao Marinha e Ambiental (CIIMAR), Universidade do Porto, Rua dos Bragas, 177, 4050-123 Porto, Portugal. Instituto de Ciencias Biomedicas Abel Salazar (ICBAS), Universidade do Porto, Portugal. ; Department of Biology, University of California Riverside, Riverside, CA 92521, USA. ; Department of Biochemistry, Molecular Biology, Entomology and Plant Pathology, Mississippi State University, Mississippi State, MS 39762, USA. Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA. ; Instituto de Ciencias Ambientales y Evolutivas, Facultad de Ciencias, Universidad Austral de Chile, Valdivia, Chile. ; Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Post Office Box 7011, S-750 07, Uppsala, Sweden. ; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Republic of Korea. Cho and Kim Genomics, Seoul National University Research Park, Seoul 151-919, Republic of Korea. Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Republic of Korea. ; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-742, Republic of Korea. ; Cho and Kim Genomics, Seoul National University Research Park, Seoul 151-919, Republic of Korea. ; State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, China. ; State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, China. College of Animal Science and Technology, China Agricultural University, Beijing 100094, China. ; Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK. ; Organisms and Environment Division, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK. Key Lab of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 China. ; International Wildlife Consultants, Carmarthen SA33 5YL, Wales, UK. ; Centre for Zoo and Wild Animal Health, Copenhagen Zoo, Roskildevej 38, DK-2000 Frederiksberg, Denmark. ; Department of Ecology and Evolutionary Biology, Tulane University, New Orleans, LA, USA. Museum of Natural Science, Louisiana State University, Baton Rouge, LA 70803, USA. ; The Genome Institute at Washington University, St. Louis, MO 63108, USA. ; College of Medicine and Forensics, Xi'an Jiaotong University, Xi'an, 710061, China. ; Institute for Genomics, Biocomputing and Biotechnology, Mississippi State University, Mississippi State, MS 39762, USA. ; Department of Biomolecular Engineering, University of California, Santa Cruz, CA 95064, USA. ; Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg, Russia. Nova Southeastern University Oceanographic Center 8000 N Ocean Drive, Dania, FL 33004, USA. ; Smithsonian Conservation Biology Institute, National Zoological Park, 1500 Remount Road, Front Royal, VA 22630, USA. ; Genetics Division, San Diego Zoo Institute for Conservation Research, 15600 San Pasqual Valley Road, Escondido, CA 92027, USA. ; Department of Vertebrate Zoology, MRC-116, National Museum of Natural History, Smithsonian Institution, Post Office Box 37012, Washington, DC 20013-7012, USA. Center for Macroecology, Evolution and Climate, the Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. ; Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, Beijing 100101, China. Swedish Species Information Centre, Swedish University of Agricultural Sciences, Box 7007, SE-750 07 Uppsala, Sweden. ; Center for Macroecology, Evolution and Climate, the Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. ; Department of Biochemistry & Biophysics, University of California, San Francisco, CA 94158, USA. ; Department of Organismic and Evolutionary Biology and Museum of Comparative Zoology, Harvard University, 26 Oxford Street, Cambridge, MA 02138, USA. ; Department of Biology and Genetics Institute, University of Florida, Gainesville, FL 32611, USA. ; Center for Macroecology, Evolution and Climate, the Natural History Museum of Denmark, University of Copenhagen, Universitetsparken 15, DK-2100 Copenhagen O, Denmark. Imperial College London, Grand Challenges in Ecosystems and the Environment Initiative, Silwood Park Campus, Ascot, Berkshire SL5 7PY, UK. ; Division of Genetics and Genomics, The Roslin Institute and Royal (Dick) School of Veterinary Studies, The Roslin Institute Building, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK. ; Department of Biology, New Mexico State University, Box 30001 MSC 3AF, Las Cruces, NM 88003, USA. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. Macau University of Science and Technology, Avenida Wai long, Taipa, Macau 999078, China. ; Department of Neurobiology, Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. zhanggj@genomics.cn jarvis@neuro.duke.edu mtpgilbert@gmail.com wangj@genomics.cn. ; Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Oster Voldgade 5-7, 1350 Copenhagen, Denmark. Trace and Environmental DNA Laboratory, Department of Environment and Agriculture, Curtin University, Perth, Western Australia, 6102, Australia. zhanggj@genomics.cn jarvis@neuro.duke.edu mtpgilbert@gmail.com wangj@genomics.cn. ; China National GeneBank, Beijing Genomics Institute (BGI)-Shenzhen, Shenzhen, 518083, China. Macau University of Science and Technology, Avenida Wai long, Taipa, Macau 999078, China. Department of Biology, University of Copenhagen, Ole Maaloes Vej 5, 2200 Copenhagen, Denmark. Princess Al Jawhara Center of Excellence in the Research of Hereditary Disorders, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Department of Medicine, University of Hong Kong, Hong Kong. zhanggj@genomics.cn jarvis@neuro.duke.edu mtpgilbert@gmail.com wangj@genomics.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504712" target="_blank"〉PubMed〈/a〉

Description: Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Won, Hyejung -- Lee, Hye-Ryeon -- Gee, Heon Yung -- Mah, Won -- Kim, Jae-Ick -- Lee, Jiseok -- Ha, Seungmin -- Chung, Changuk -- Jung, Eun Suk -- Cho, Yi Sul -- Park, Sae-Geun -- Lee, Jung-Soo -- Lee, Kyungmin -- Kim, Daesoo -- Bae, Yong Chul -- Kaang, Bong-Kiun -- Lee, Min Goo -- Kim, Eunjoon -- England -- Nature. 2012 Jun 13;486(7402):261-5. doi: 10.1038/nature11208.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biological Sciences, KAIST, Daejeon 305-701, Korea.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22699620" target="_blank"〉PubMed〈/a〉

Description: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in 〉100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P 〈 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039276/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039276/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Teslovich, Tanya M -- Musunuru, Kiran -- Smith, Albert V -- Edmondson, Andrew C -- Stylianou, Ioannis M -- Koseki, Masahiro -- Pirruccello, James P -- Ripatti, Samuli -- Chasman, Daniel I -- Willer, Cristen J -- Johansen, Christopher T -- Fouchier, Sigrid W -- Isaacs, Aaron -- Peloso, Gina M -- Barbalic, Maja -- Ricketts, Sally L -- Bis, Joshua C -- Aulchenko, Yurii S -- Thorleifsson, Gudmar -- Feitosa, Mary F -- Chambers, John -- Orho-Melander, Marju -- Melander, Olle -- Johnson, Toby -- Li, Xiaohui -- Guo, Xiuqing -- Li, Mingyao -- Shin Cho, Yoon -- Jin Go, Min -- Jin Kim, Young -- Lee, Jong-Young -- Park, Taesung -- Kim, Kyunga -- Sim, Xueling -- Twee-Hee Ong, Rick -- Croteau-Chonka, Damien C -- Lange, Leslie A -- Smith, Joshua D -- Song, Kijoung -- Hua Zhao, Jing -- Yuan, Xin -- Luan, Jian'an -- Lamina, Claudia -- Ziegler, Andreas -- Zhang, Weihua -- Zee, Robert Y L -- Wright, Alan F -- Witteman, Jacqueline C M -- Wilson, James F -- Willemsen, Gonneke -- Wichmann, H-Erich -- Whitfield, John B -- Waterworth, Dawn M -- Wareham, Nicholas J -- Waeber, Gerard -- Vollenweider, Peter -- Voight, Benjamin F -- Vitart, Veronique -- Uitterlinden, Andre G -- Uda, Manuela -- Tuomilehto, Jaakko -- Thompson, John R -- Tanaka, Toshiko -- Surakka, Ida -- Stringham, Heather M -- Spector, Tim D -- Soranzo, Nicole -- Smit, Johannes H -- Sinisalo, Juha -- Silander, Kaisa -- Sijbrands, Eric J G -- Scuteri, Angelo -- Scott, James -- Schlessinger, David -- Sanna, Serena -- Salomaa, Veikko -- Saharinen, Juha -- Sabatti, Chiara -- Ruokonen, Aimo -- Rudan, Igor -- Rose, Lynda M -- Roberts, Robert -- Rieder, Mark -- Psaty, Bruce M -- Pramstaller, Peter P -- Pichler, Irene -- Perola, Markus -- Penninx, Brenda W J H -- Pedersen, Nancy L -- Pattaro, Cristian -- Parker, Alex N -- Pare, Guillaume -- Oostra, Ben A -- O'Donnell, Christopher J -- Nieminen, Markku S -- Nickerson, Deborah A -- Montgomery, Grant W -- Meitinger, Thomas -- McPherson, Ruth -- McCarthy, Mark I -- McArdle, Wendy -- Masson, David -- Martin, Nicholas G -- Marroni, Fabio -- Mangino, Massimo -- Magnusson, Patrik K E -- Lucas, Gavin -- Luben, Robert -- Loos, Ruth J F -- Lokki, Marja-Liisa -- Lettre, Guillaume -- Langenberg, Claudia -- Launer, Lenore J -- Lakatta, Edward G -- Laaksonen, Reijo -- Kyvik, Kirsten O -- Kronenberg, Florian -- Konig, Inke R -- Khaw, Kay-Tee -- Kaprio, Jaakko -- Kaplan, Lee M -- Johansson, Asa -- Jarvelin, Marjo-Riitta -- Janssens, A Cecile J W -- Ingelsson, Erik -- Igl, Wilmar -- Kees Hovingh, G -- Hottenga, Jouke-Jan -- Hofman, Albert -- Hicks, Andrew A -- Hengstenberg, Christian -- Heid, Iris M -- Hayward, Caroline -- Havulinna, Aki S -- Hastie, Nicholas D -- Harris, Tamara B -- Haritunians, Talin -- Hall, Alistair S -- Gyllensten, Ulf -- Guiducci, Candace -- Groop, Leif C -- Gonzalez, Elena -- Gieger, Christian -- Freimer, Nelson B -- Ferrucci, Luigi -- Erdmann, Jeanette -- Elliott, Paul -- Ejebe, Kenechi G -- Doring, Angela -- Dominiczak, Anna F -- Demissie, Serkalem -- Deloukas, Panagiotis -- de Geus, Eco J C -- de Faire, Ulf -- Crawford, Gabriel -- Collins, Francis S -- Chen, Yii-der I -- Caulfield, Mark J -- Campbell, Harry -- Burtt, Noel P -- Bonnycastle, Lori L -- Boomsma, Dorret I -- Boekholdt, S Matthijs -- Bergman, Richard N -- Barroso, Ines -- Bandinelli, Stefania -- Ballantyne, Christie M -- Assimes, Themistocles L -- Quertermous, Thomas -- Altshuler, David -- Seielstad, Mark -- Wong, Tien Y -- Tai, E-Shyong -- Feranil, Alan B -- Kuzawa, Christopher W -- Adair, Linda S -- Taylor, Herman A Jr -- Borecki, Ingrid B -- Gabriel, Stacey B -- Wilson, James G -- Holm, Hilma -- Thorsteinsdottir, Unnur -- Gudnason, Vilmundur -- Krauss, Ronald M -- Mohlke, Karen L -- Ordovas, Jose M -- Munroe, Patricia B -- Kooner, Jaspal S -- Tall, Alan R -- Hegele, Robert A -- Kastelein, John J P -- Schadt, Eric E -- Rotter, Jerome I -- Boerwinkle, Eric -- Strachan, David P -- Mooser, Vincent -- Stefansson, Kari -- Reilly, Muredach P -- Samani, Nilesh J -- Schunkert, Heribert -- Cupples, L Adrienne -- Sandhu, Manjinder S -- Ridker, Paul M -- Rader, Daniel J -- van Duijn, Cornelia M -- Peltonen, Leena -- Abecasis, Goncalo R -- Boehnke, Michael -- Kathiresan, Sekar -- 068545/Z/02/Wellcome Trust/United Kingdom -- 076113/B/04/Z/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 1Z01 HG000024/HG/NHGRI NIH HHS/ -- 5R01DK06833603/DK/NIDDK NIH HHS/ -- 5R01DK07568102/DK/NIDDK NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01HL08770003/HL/NHLBI NIH HHS/ -- 5R01HL08821502/HL/NHLBI NIH HHS/ -- CA 047988/CA/NCI NIH HHS/ -- CZB/4/710/Chief Scientist Office/United Kingdom -- DK062370/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK072193/DK/NIDDK NIH HHS/ -- DK078150/DK/NIDDK NIH HHS/ -- DK56350/DK/NIDDK NIH HHS/ -- ES10126/ES/NIEHS NIH HHS/ -- G0000934/Medical Research Council/United Kingdom -- G0401527/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G0801566/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- G9521010D/Medical Research Council/United Kingdom -- HHSN268200625226C/PHS HHS/ -- HL 04381/HL/NHLBI NIH HHS/ -- HL 080467/HL/NHLBI NIH HHS/ -- HL-54776/HL/NHLBI NIH HHS/ -- HL085144/HL/NHLBI NIH HHS/ -- K99 HL098364/HL/NHLBI NIH HHS/ -- K99 HL098364-01/HL/NHLBI NIH HHS/ -- K99HL094535/HL/NHLBI NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- MC_QA137934/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- MC_U127561128/Medical Research Council/United Kingdom -- N01 HC-15103/HC/NHLBI NIH HHS/ -- N01 HC-55222/HC/NHLBI NIH HHS/ -- N01-AG-12100/AG/NIA NIH HHS/ -- N01-HC-25195/HC/NHLBI NIH HHS/ -- N01-HC-35129/HC/NHLBI NIH HHS/ -- N01-HC-45133/HC/NHLBI NIH HHS/ -- N01-HC-55015/HC/NHLBI NIH HHS/ -- N01-HC-55016/HC/NHLBI NIH HHS/ -- N01-HC-55018/HC/NHLBI NIH HHS/ -- N01-HC-55019/HC/NHLBI NIH HHS/ -- N01-HC-55020/HC/NHLBI NIH HHS/ -- N01-HC-55021/HC/NHLBI NIH HHS/ -- N01-HC-55022/HC/NHLBI NIH HHS/ -- N01-HC-75150/HC/NHLBI NIH HHS/ -- N01-HC-85079/HC/NHLBI NIH HHS/ -- N01-HC-85080/HC/NHLBI NIH HHS/ -- N01-HC-85081/HC/NHLBI NIH HHS/ -- N01-HC-85082/HC/NHLBI NIH HHS/ -- N01-HC-85083/HC/NHLBI NIH HHS/ -- N01-HC-85084/HC/NHLBI NIH HHS/ -- N01-HC-85085/HC/NHLBI NIH HHS/ -- N01-HC-85086/HC/NHLBI NIH HHS/ -- N01-HG-65403/HG/NHGRI NIH HHS/ -- N02-HL-6-4278/HL/NHLBI NIH HHS/ -- PG/02/128/British Heart Foundation/United Kingdom -- PG/08/094/British Heart Foundation/United Kingdom -- PG/08/094/26019/British Heart Foundation/United Kingdom -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087676/HL/NHLBI NIH HHS/ -- R01 HL089650/HL/NHLBI NIH HHS/ -- R01HL086694/HL/NHLBI NIH HHS/ -- R01HL087641/HL/NHLBI NIH HHS/ -- R01HL087652/HL/NHLBI NIH HHS/ -- R01HL59367/HL/NHLBI NIH HHS/ -- R24 HD050924/HD/NICHD NIH HHS/ -- RC1 HL099634/HL/NHLBI NIH HHS/ -- RC1 HL099634-02/HL/NHLBI NIH HHS/ -- RC1 HL099793/HL/NHLBI NIH HHS/ -- RC2 HL101864,/HL/NHLBI NIH HHS/ -- RC2 HL102419/HL/NHLBI NIH HHS/ -- RG/07/005/23633/British Heart Foundation/United Kingdom -- RR20649/RR/NCRR NIH HHS/ -- SP/08/005/25115/British Heart Foundation/United Kingdom -- T32 GM007092/GM/NIGMS NIH HHS/ -- T32 HG00040/HG/NHGRI NIH HHS/ -- T32HL007208/HL/NHLBI NIH HHS/ -- TW05596/TW/FIC NIH HHS/ -- U01 DK062370/DK/NIDDK NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 HL069757/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01HG004402/HG/NHGRI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1RR025005/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):707-13. doi: 10.1038/nature09270.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686565" target="_blank"〉PubMed〈/a〉

Description: Algorithms designed to identify canonical yeast prions predict that around 250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbour a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here we define pathogenic mutations in PrLDs of heterogeneous nuclear ribonucleoproteins (hnRNPs) A2B1 and A1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and in one case of familial amyotrophic lateral sclerosis. Wild-type hnRNPA2 (the most abundant isoform of hnRNPA2B1) and hnRNPA1 show an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a 'steric zipper' motif in the PrLD, which accelerates the formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Notably, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant steric zipper motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs should therefore be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756911/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756911/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Hong Joo -- Kim, Nam Chul -- Wang, Yong-Dong -- Scarborough, Emily A -- Moore, Jennifer -- Diaz, Zamia -- MacLea, Kyle S -- Freibaum, Brian -- Li, Songqing -- Molliex, Amandine -- Kanagaraj, Anderson P -- Carter, Robert -- Boylan, Kevin B -- Wojtas, Aleksandra M -- Rademakers, Rosa -- Pinkus, Jack L -- Greenberg, Steven A -- Trojanowski, John Q -- Traynor, Bryan J -- Smith, Bradley N -- Topp, Simon -- Gkazi, Athina-Soragia -- Miller, Jack -- Shaw, Christopher E -- Kottlors, Michael -- Kirschner, Janbernd -- Pestronk, Alan -- Li, Yun R -- Ford, Alice Flynn -- Gitler, Aaron D -- Benatar, Michael -- King, Oliver D -- Kimonis, Virginia E -- Ross, Eric D -- Weihl, Conrad C -- Shorter, James -- Taylor, J Paul -- 089701/Wellcome Trust/United Kingdom -- AG031867/AG/NIA NIH HHS/ -- AG032953/AG/NIA NIH HHS/ -- DP2OD002177/OD/NIH HHS/ -- G0900688/Medical Research Council/United Kingdom -- K02 AG042095/AG/NIA NIH HHS/ -- MC_G1000733/Medical Research Council/United Kingdom -- NS053825/NS/NINDS NIH HHS/ -- NS067354/NS/NINDS NIH HHS/ -- P01 AG032953/AG/NIA NIH HHS/ -- R01 AG031867/AG/NIA NIH HHS/ -- R01 NS053825/NS/NINDS NIH HHS/ -- England -- Nature. 2013 Mar 28;495(7442):467-73. doi: 10.1038/nature11922. Epub 2013 Mar 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38120, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23455423" target="_blank"〉PubMed〈/a〉

Description: Silent information regulator 2 (Sir2) proteins (sirtuins) are nicotinamide adenine dinucleotide-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, Sirt1 to Sirt7. Four of them (Sirt4 to Sirt7) have no detectable or very weak deacetylase activity. We found that Sirt5 is an efficient protein lysine desuccinylase and demalonylase in vitro. The preference for succinyl and malonyl groups was explained by the presence of an arginine residue (Arg(105)) and tyrosine residue (Tyr(102)) in the acyl pocket of Sirt5. Several mammalian proteins were identified with mass spectrometry to have succinyl or malonyl lysine modifications. Deletion of Sirt5 in mice appeared to increase the level of succinylation on carbamoyl phosphate synthase 1, which is a known target of Sirt5. Thus, protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217313/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217313/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Du, Jintang -- Zhou, Yeyun -- Su, Xiaoyang -- Yu, Jiu Jiu -- Khan, Saba -- Jiang, Hong -- Kim, Jungwoo -- Woo, Jimin -- Kim, Jun Huyn -- Choi, Brian Hyun -- He, Bin -- Chen, Wei -- Zhang, Sheng -- Cerione, Richard A -- Auwerx, Johan -- Hao, Quan -- Lin, Hening -- 231138/European Research Council/International -- DK58920/DK/NIDDK NIH HHS/ -- P41 RR001646/RR/NCRR NIH HHS/ -- P41 RR001646-27/RR/NCRR NIH HHS/ -- R01 GM086703/GM/NIGMS NIH HHS/ -- R01 GM086703-03/GM/NIGMS NIH HHS/ -- R01 GM086703-03S1/GM/NIGMS NIH HHS/ -- R01GM086703/GM/NIGMS NIH HHS/ -- RR01646/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2011 Nov 11;334(6057):806-9. doi: 10.1126/science.1207861.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22076378" target="_blank"〉PubMed〈/a〉

Description: Most cancer cells are characterized by aneuploidy, an abnormal number of chromosomes. We have identified a clue to the mechanistic origins of aneuploidy through integrative genomic analyses of human tumors. A diverse range of tumor types were found to harbor deletions or inactivating mutations of STAG2, a gene encoding a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Because STAG2 is on the X chromosome, its inactivation requires only a single mutational event. Studying a near-diploid human cell line with a stable karyotype, we found that targeted inactivation of STAG2 led to chromatid cohesion defects and aneuploidy, whereas in two aneuploid human glioblastoma cell lines, targeted correction of the endogenous mutant alleles of STAG2 led to enhanced chromosomal stability. Thus, genetic disruption of cohesin is a cause of aneuploidy in human cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374335/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374335/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Solomon, David A -- Kim, Taeyeon -- Diaz-Martinez, Laura A -- Fair, Joshlean -- Elkahloun, Abdel G -- Harris, Brent T -- Toretsky, Jeffrey A -- Rosenberg, Steven A -- Shukla, Neerav -- Ladanyi, Marc -- Samuels, Yardena -- James, C David -- Yu, Hongtao -- Kim, Jung-Sik -- Waldman, Todd -- CA097257/CA/NCI NIH HHS/ -- R01 CA133662/CA/NCI NIH HHS/ -- R01 CA138212/CA/NCI NIH HHS/ -- R01 CA169345/CA/NCI NIH HHS/ -- R01CA115699/CA/NCI NIH HHS/ -- R21CA143282/CA/NCI NIH HHS/ -- Z01 HG200337-01/Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Aug 19;333(6045):1039-43. doi: 10.1126/science.1203619.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University School of Medicine, Washington, DC 20057, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21852505" target="_blank"〉PubMed〈/a〉

Description: The NAD-dependent deacetylase Sir2 was initially identified as a mediator of replicative lifespan in budding yeast and was subsequently shown to modulate longevity in worms and flies. Its mammalian homologue, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. Recent studies suggest a functional relevance of SIRT1 in normal brain physiology and neurological disorders. However, it is unknown if SIRT1 has a role in higher-order brain functions. We report that SIRT1 modulates synaptic plasticity and memory formation via a microRNA-mediated mechanism. Activation of SIRT1 enhances, whereas its loss-of-function impairs, synaptic plasticity. Surprisingly, these effects were mediated via post-transcriptional regulation of cAMP response binding protein (CREB) expression by a brain-specific microRNA, miR-134. SIRT1 normally functions to limit expression of miR-134 via a repressor complex containing the transcription factor YY1, and unchecked miR-134 expression following SIRT1 deficiency results in the downregulated expression of CREB and brain-derived neurotrophic factor (BDNF), thereby impairing synaptic plasticity. These findings demonstrate a new role for SIRT1 in cognition and a previously unknown microRNA-based mechanism by which SIRT1 regulates these processes. Furthermore, these results describe a separate branch of SIRT1 signalling, in which SIRT1 has a direct role in regulating normal brain function in a manner that is disparate from its cell survival functions, demonstrating its value as a potential therapeutic target for the treatment of central nervous system disorders.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928875/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928875/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gao, Jun -- Wang, Wen-Yuan -- Mao, Ying-Wei -- Graff, Johannes -- Guan, Ji-Song -- Pan, Ling -- Mak, Gloria -- Kim, Dohoon -- Su, Susan C -- Tsai, Li-Huei -- P01 AG027916/AG/NIA NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 26;466(7310):1105-9. doi: 10.1038/nature09271. Epub 2010 Jul 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20622856" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Alison M -- Tingen, Candace M -- Woodruff, Teresa K -- England -- Nature. 2010 Jun 10;465(7299):688-9. doi: 10.1038/465688a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535184" target="_blank"〉PubMed〈/a〉

Description: Monozygotic or 'identical' twins have been widely studied to dissect the relative contributions of genetics and environment in human diseases. In multiple sclerosis (MS), an autoimmune demyelinating disease and common cause of neurodegeneration and disability in young adults, disease discordance in monozygotic twins has been interpreted to indicate environmental importance in its pathogenesis. However, genetic and epigenetic differences between monozygotic twins have been described, challenging the accepted experimental model in disambiguating the effects of nature and nurture. Here we report the genome sequences of one MS-discordant monozygotic twin pair, and messenger RNA transcriptome and epigenome sequences of CD4(+) lymphocytes from three MS-discordant, monozygotic twin pairs. No reproducible differences were detected between co-twins among approximately 3.6 million single nucleotide polymorphisms (SNPs) or approximately 0.2 million insertion-deletion polymorphisms. Nor were any reproducible differences observed between siblings of the three twin pairs in HLA haplotypes, confirmed MS-susceptibility SNPs, copy number variations, mRNA and genomic SNP and insertion-deletion genotypes, or the expression of approximately 19,000 genes in CD4(+) T cells. Only 2 to 176 differences in the methylation of approximately 2 million CpG dinucleotides were detected between siblings of the three twin pairs, in contrast to approximately 800 methylation differences between T cells of unrelated individuals and several thousand differences between tissues or between normal and cancerous tissues. In the first systematic effort to estimate sequence variation among monozygotic co-twins, we did not find evidence for genetic, epigenetic or transcriptome differences that explained disease discordance. These are the first, to our knowledge, female, twin and autoimmune disease individual genome sequences reported.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862593/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862593/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baranzini, Sergio E -- Mudge, Joann -- van Velkinburgh, Jennifer C -- Khankhanian, Pouya -- Khrebtukova, Irina -- Miller, Neil A -- Zhang, Lu -- Farmer, Andrew D -- Bell, Callum J -- Kim, Ryan W -- May, Gregory D -- Woodward, Jimmy E -- Caillier, Stacy J -- McElroy, Joseph P -- Gomez, Refujia -- Pando, Marcelo J -- Clendenen, Leonda E -- Ganusova, Elena E -- Schilkey, Faye D -- Ramaraj, Thiruvarangan -- Khan, Omar A -- Huntley, Jim J -- Luo, Shujun -- Kwok, Pui-Yan -- Wu, Thomas D -- Schroth, Gary P -- Oksenberg, Jorge R -- Hauser, Stephen L -- Kingsmore, Stephen F -- P20 RR016480/RR/NCRR NIH HHS/ -- P20 RR016480-09/RR/NCRR NIH HHS/ -- R01 NS026799/NS/NINDS NIH HHS/ -- R01 NS026799-20A1/NS/NINDS NIH HHS/ -- R01 NS046297/NS/NINDS NIH HHS/ -- R01 NS046297-06/NS/NINDS NIH HHS/ -- R01NS26799/NS/NINDS NIH HHS/ -- R01NS46297/NS/NINDS NIH HHS/ -- RR016480/RR/NCRR NIH HHS/ -- U01 AI066569/AI/NIAID NIH HHS/ -- U01 AI066569-05/AI/NIAID NIH HHS/ -- U19 HD077693/HD/NICHD NIH HHS/ -- England -- Nature. 2010 Apr 29;464(7293):1351-6. doi: 10.1038/nature08990.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of California at San Francisco, San Francisco, California 94143, USA. sebaran@cgl.ucsf.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20428171" target="_blank"〉PubMed〈/a〉

Description: The causes of amyotrophic lateral sclerosis (ALS), a devastating human neurodegenerative disease, are poorly understood, although the protein TDP-43 has been suggested to have a critical role in disease pathogenesis. Here we show that ataxin 2 (ATXN2), a polyglutamine (polyQ) protein mutated in spinocerebellar ataxia type 2, is a potent modifier of TDP-43 toxicity in animal and cellular models. ATXN2 and TDP-43 associate in a complex that depends on RNA. In spinal cord neurons of ALS patients, ATXN2 is abnormally localized; likewise, TDP-43 shows mislocalization in spinocerebellar ataxia type 2. To assess the involvement of ATXN2 in ALS, we analysed the length of the polyQ repeat in the ATXN2 gene in 915 ALS patients. We found that intermediate-length polyQ expansions (27-33 glutamines) in ATXN2 were significantly associated with ALS. These data establish ATXN2 as a relatively common ALS susceptibility gene. Furthermore, these findings indicate that the TDP-43-ATXN2 interaction may be a promising target for therapeutic intervention in ALS and other TDP-43 proteinopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965417/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965417/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Elden, Andrew C -- Kim, Hyung-Jun -- Hart, Michael P -- Chen-Plotkin, Alice S -- Johnson, Brian S -- Fang, Xiaodong -- Armakola, Maria -- Geser, Felix -- Greene, Robert -- Lu, Min Min -- Padmanabhan, Arun -- Clay-Falcone, Dana -- McCluskey, Leo -- Elman, Lauren -- Juhr, Denise -- Gruber, Peter J -- Rub, Udo -- Auburger, Georg -- Trojanowski, John Q -- Lee, Virginia M-Y -- Van Deerlin, Vivianna M -- Bonini, Nancy M -- Gitler, Aaron D -- 1DP2OD004417-01/OD/NIH HHS/ -- 1R01NS065317-01/NS/NINDS NIH HHS/ -- AG-10124/AG/NIA NIH HHS/ -- AG-17586/AG/NIA NIH HHS/ -- DP2 OD004417/OD/NIH HHS/ -- DP2 OD004417-01/OD/NIH HHS/ -- K08 AG-033101-01/AG/NIA NIH HHS/ -- P01 AG-09215/AG/NIA NIH HHS/ -- R01 NS065317/NS/NINDS NIH HHS/ -- R01 NS065317-01/NS/NINDS NIH HHS/ -- R01 NS065317-02/NS/NINDS NIH HHS/ -- R01 NS065317-03/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 26;466(7310):1069-75. doi: 10.1038/nature09320.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20740007" target="_blank"〉PubMed〈/a〉