ALBERT

Description: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (〉/=140 mm Hg systolic blood pressure or 〉/=90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340926/" 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/PMC3340926/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Consortium for Blood Pressure Genome-Wide Association Studies -- Ehret, Georg B -- Munroe, Patricia B -- Rice, Kenneth M -- Bochud, Murielle -- Johnson, Andrew D -- Chasman, Daniel I -- Smith, Albert V -- Tobin, Martin D -- Verwoert, Germaine C -- Hwang, Shih-Jen -- Pihur, Vasyl -- Vollenweider, Peter -- O'Reilly, Paul F -- Amin, Najaf -- Bragg-Gresham, Jennifer L -- Teumer, Alexander -- Glazer, Nicole L -- Launer, Lenore -- Zhao, Jing Hua -- Aulchenko, Yurii -- Heath, Simon -- Sober, Siim -- Parsa, Afshin -- Luan, Jian'an -- Arora, Pankaj -- Dehghan, Abbas -- Zhang, Feng -- Lucas, Gavin -- Hicks, Andrew A -- Jackson, Anne U -- Peden, John F -- Tanaka, Toshiko -- Wild, Sarah H -- Rudan, Igor -- Igl, Wilmar -- Milaneschi, Yuri -- Parker, Alex N -- Fava, Cristiano -- Chambers, John C -- Fox, Ervin R -- Kumari, Meena -- Go, Min Jin -- van der Harst, Pim -- Kao, Wen Hong Linda -- Sjogren, Marketa -- Vinay, D G -- Alexander, Myriam -- Tabara, Yasuharu -- Shaw-Hawkins, Sue -- Whincup, Peter H -- Liu, Yongmei -- Shi, Gang -- Kuusisto, Johanna -- Tayo, Bamidele -- Seielstad, Mark -- Sim, Xueling -- Nguyen, Khanh-Dung Hoang -- Lehtimaki, Terho -- Matullo, Giuseppe -- Wu, Ying -- Gaunt, Tom R -- Onland-Moret, N Charlotte -- Cooper, Matthew N -- Platou, Carl G P -- Org, Elin -- Hardy, Rebecca -- Dahgam, Santosh -- Palmen, Jutta -- Vitart, Veronique -- Braund, Peter S -- Kuznetsova, Tatiana -- Uiterwaal, Cuno S P M -- Adeyemo, Adebowale -- Palmas, Walter -- Campbell, Harry -- Ludwig, Barbara -- Tomaszewski, Maciej -- Tzoulaki, Ioanna -- Palmer, Nicholette D -- CARDIoGRAM consortium -- CKDGen Consortium -- KidneyGen Consortium -- EchoGen consortium -- CHARGE-HF consortium -- Aspelund, Thor -- Garcia, Melissa -- Chang, Yen-Pei C -- O'Connell, Jeffrey R -- Steinle, Nanette I -- Grobbee, Diederick E -- Arking, Dan E -- Kardia, Sharon L -- Morrison, Alanna C -- Hernandez, Dena -- Najjar, Samer -- McArdle, Wendy L -- Hadley, David -- Brown, Morris J -- Connell, John M -- Hingorani, Aroon D -- Day, Ian N M -- Lawlor, Debbie A -- Beilby, John P -- Lawrence, Robert W -- Clarke, Robert -- Hopewell, Jemma C -- Ongen, Halit -- Dreisbach, Albert W -- Li, Yali -- Young, J Hunter -- Bis, Joshua C -- Kahonen, Mika -- Viikari, Jorma -- Adair, Linda S -- Lee, Nanette R -- Chen, Ming-Huei -- Olden, Matthias -- Pattaro, Cristian -- Bolton, Judith A Hoffman -- Kottgen, Anna -- Bergmann, Sven -- Mooser, Vincent -- Chaturvedi, Nish -- Frayling, Timothy M -- Islam, Muhammad -- Jafar, Tazeen H -- Erdmann, Jeanette -- Kulkarni, Smita R -- Bornstein, Stefan R -- Grassler, Jurgen -- Groop, Leif -- Voight, Benjamin F -- Kettunen, Johannes -- Howard, Philip -- Taylor, Andrew -- Guarrera, Simonetta -- Ricceri, Fulvio -- Emilsson, Valur -- Plump, Andrew -- Barroso, Ines -- Khaw, Kay-Tee -- Weder, Alan B -- Hunt, Steven C -- Sun, Yan V -- Bergman, Richard N -- Collins, Francis S -- Bonnycastle, Lori L -- Scott, Laura J -- Stringham, Heather M -- Peltonen, Leena -- Perola, Markus -- Vartiainen, Erkki -- Brand, Stefan-Martin -- Staessen, Jan A -- Wang, Thomas J -- Burton, Paul R -- Soler Artigas, Maria -- Dong, Yanbin -- Snieder, Harold -- Wang, Xiaoling -- Zhu, Haidong -- Lohman, Kurt K -- Rudock, Megan E -- Heckbert, Susan R -- Smith, Nicholas L -- Wiggins, Kerri L -- Doumatey, Ayo -- Shriner, Daniel -- Veldre, Gudrun -- Viigimaa, Margus -- Kinra, Sanjay -- Prabhakaran, Dorairaj -- Tripathy, Vikal -- Langefeld, Carl D -- Rosengren, Annika -- Thelle, Dag S -- Corsi, Anna Maria -- Singleton, Andrew -- Forrester, Terrence -- Hilton, Gina -- McKenzie, Colin A -- Salako, Tunde -- Iwai, Naoharu -- Kita, Yoshikuni -- Ogihara, Toshio -- Ohkubo, Takayoshi -- Okamura, Tomonori -- Ueshima, Hirotsugu -- Umemura, Satoshi -- Eyheramendy, Susana -- Meitinger, Thomas -- Wichmann, H-Erich -- Cho, Yoon Shin -- Kim, Hyung-Lae -- Lee, Jong-Young -- Scott, James -- Sehmi, Joban S -- Zhang, Weihua -- Hedblad, Bo -- Nilsson, Peter -- Smith, George Davey -- Wong, Andrew -- Narisu, Narisu -- Stancakova, Alena -- Raffel, Leslie J -- Yao, Jie -- Kathiresan, Sekar -- O'Donnell, Christopher J -- Schwartz, Stephen M -- Ikram, M Arfan -- Longstreth, W T Jr -- Mosley, Thomas H -- Seshadri, Sudha -- Shrine, Nick R G -- Wain, Louise V -- Morken, Mario A -- Swift, Amy J -- Laitinen, Jaana -- Prokopenko, Inga -- Zitting, Paavo -- Cooper, Jackie A -- Humphries, Steve E -- Danesh, John -- Rasheed, Asif -- Goel, Anuj -- Hamsten, Anders -- Watkins, Hugh -- Bakker, Stephan J L -- van Gilst, Wiek H -- Janipalli, Charles S -- Mani, K Radha -- Yajnik, Chittaranjan S -- Hofman, Albert -- Mattace-Raso, Francesco U S -- Oostra, Ben A -- Demirkan, Ayse -- Isaacs, Aaron -- Rivadeneira, Fernando -- Lakatta, Edward G -- Orru, Marco -- Scuteri, Angelo -- Ala-Korpela, Mika -- Kangas, Antti J -- Lyytikainen, Leo-Pekka -- Soininen, Pasi -- Tukiainen, Taru -- Wurtz, Peter -- Ong, Rick Twee-Hee -- Dorr, Marcus -- Kroemer, Heyo K -- Volker, Uwe -- Volzke, Henry -- Galan, Pilar -- Hercberg, Serge -- Lathrop, Mark -- Zelenika, Diana -- Deloukas, Panos -- Mangino, Massimo -- Spector, Tim D -- Zhai, Guangju -- Meschia, James F -- Nalls, Michael A -- Sharma, Pankaj -- Terzic, Janos -- Kumar, M V Kranthi -- Denniff, Matthew -- Zukowska-Szczechowska, Ewa -- Wagenknecht, Lynne E -- Fowkes, F Gerald R -- Charchar, Fadi J -- Schwarz, Peter E H -- Hayward, Caroline -- Guo, Xiuqing -- Rotimi, Charles -- Bots, Michiel L -- Brand, Eva -- Samani, Nilesh J -- Polasek, Ozren -- Talmud, Philippa J -- Nyberg, Fredrik -- Kuh, Diana -- Laan, Maris -- Hveem, Kristian -- Palmer, Lyle J -- van der Schouw, Yvonne T -- Casas, Juan P -- Mohlke, Karen L -- Vineis, Paolo -- Raitakari, Olli -- Ganesh, Santhi K -- Wong, Tien Y -- Tai, E Shyong -- Cooper, Richard S -- Laakso, Markku -- Rao, Dabeeru C -- Harris, Tamara B -- Morris, Richard W -- Dominiczak, Anna F -- Kivimaki, Mika -- Marmot, Michael G -- Miki, Tetsuro -- Saleheen, Danish -- Chandak, Giriraj R -- Coresh, Josef -- Navis, Gerjan -- Salomaa, Veikko -- Han, Bok-Ghee -- Zhu, Xiaofeng -- Kooner, Jaspal S -- Melander, Olle -- Ridker, Paul M -- Bandinelli, Stefania -- Gyllensten, Ulf B -- Wright, Alan F -- Wilson, James F -- Ferrucci, Luigi -- Farrall, Martin -- Tuomilehto, Jaakko -- Pramstaller, Peter P -- Elosua, Roberto -- Soranzo, Nicole -- Sijbrands, Eric J G -- Altshuler, David -- Loos, Ruth J F -- Shuldiner, Alan R -- Gieger, Christian -- Meneton, Pierre -- Uitterlinden, Andre G -- Wareham, Nicholas J -- Gudnason, Vilmundur -- Rotter, Jerome I -- Rettig, Rainer -- Uda, Manuela -- Strachan, David P -- Witteman, Jacqueline C M -- Hartikainen, Anna-Liisa -- Beckmann, Jacques S -- Boerwinkle, Eric -- Vasan, Ramachandran S -- Boehnke, Michael -- Larson, Martin G -- Jarvelin, Marjo-Riitta -- Psaty, Bruce M -- Abecasis, Goncalo R -- Chakravarti, Aravinda -- Elliott, Paul -- van Duijn, Cornelia M -- Newton-Cheh, Christopher -- Levy, Daniel -- Caulfield, Mark J -- Johnson, Toby -- 068545/Z/02/Wellcome Trust/United Kingdom -- 070191/Z/03/Z/Wellcome Trust/United Kingdom -- 077016/Z/05/Z/Wellcome Trust/United Kingdom -- 079895/Wellcome Trust/United Kingdom -- 080747/Z/06/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 1R01AG032098-01A/AG/NIA NIH HHS/ -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 263 MD 821336/MD/NIMHD NIH HHS/ -- 263 MD 9164/MD/NIMHD NIH HHS/ -- 263-MA-410953/PHS HHS/ -- 2M01RR010284/RR/NCRR NIH HHS/ -- 33014/PHS HHS/ -- 55005617/Howard Hughes Medical Institute/ -- 5R01HL086694-03/HL/NHLBI NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01HL08770002/HL/NHLBI NIH HHS/ -- 5R01MH63706:02/MH/NIMH NIH HHS/ -- 5U01CA086308/CA/NCI NIH HHS/ -- AG13196/AG/NIA NIH HHS/ -- CH/03/001/British Heart Foundation/United Kingdom -- CZB/4/276/Chief Scientist Office/United Kingdom -- CZB/4/710/Chief Scientist Office/United Kingdom -- DK062370/DK/NIDDK NIH HHS/ -- DK063491/DK/NIDDK NIH HHS/ -- DK072193/DK/NIDDK NIH HHS/ -- DK075787/DK/NIDDK NIH HHS/ -- DK078150/DK/NIDDK NIH HHS/ -- DK56350/DK/NIDDK NIH HHS/ -- ES10126/ES/NIEHS NIH HHS/ -- FS05/125/British Heart Foundation/United Kingdom -- G0000934/Medical Research Council/United Kingdom -- G0100222/Medical Research Council/United Kingdom -- G0400874/Medical Research Council/United Kingdom -- G0401527/Medical Research Council/United Kingdom -- G0500539/Medical Research Council/United Kingdom -- G0501942/British Heart Foundation/United Kingdom -- G0501942/Medical Research Council/United Kingdom -- G0600331/Medical Research Council/United Kingdom -- G0600705/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 -- G0902037/Medical Research Council/United Kingdom -- G0902313/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- G19/35/Medical Research Council/United Kingdom -- G20234/Biotechnology and Biological Sciences Research Council/United Kingdom -- G8802774/Medical Research Council/United Kingdom -- G9521010/Medical Research Council/United Kingdom -- G9521010D/Medical Research Council/United Kingdom -- HG003054/HG/NHGRI NIH HHS/ -- HG005581/HG/NHGRI NIH HHS/ -- HHSN268200625226C/PHS HHS/ -- HHSN268200782096/PHS HHS/ -- HHSN268200782096C/PHS HHS/ -- HL 54512/HL/NHLBI NIH HHS/ -- HL-87660/HL/NHLBI NIH HHS/ -- HL043851/HL/NHLBI NIH HHS/ -- HL080025/HL/NHLBI NIH HHS/ -- HL084729/HL/NHLBI NIH HHS/ -- HL085144/HL/NHLBI NIH HHS/ -- HL086718/HL/NHLBI NIH HHS/ -- HL087647/HL/NHLBI NIH HHS/ -- HL098283/HL/NHLBI NIH HHS/ -- HL36310/HL/NHLBI NIH HHS/ -- HL45508/HL/NHLBI NIH HHS/ -- HL53353/HL/NHLBI NIH HHS/ -- HL54512/HL/NHLBI NIH HHS/ -- HS06516/HS/AHRQ HHS/ -- K12RR023250/RR/NCRR NIH HHS/ -- M01 RR16500/RR/NCRR NIH HHS/ -- M01-RR00425/RR/NCRR NIH HHS/ -- MC_PC_U127561128/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- MC_U123092720/Medical Research Council/United Kingdom -- MC_U123092723/Medical Research Council/United Kingdom -- MC_U127561128/Medical Research Council/United Kingdom -- MC_U137686857/Medical Research Council/United Kingdom -- MC_UP_A100_1003/Medical Research Council/United Kingdom -- MOP-82810/Canadian Institutes of Health Research/Canada -- MOP172605/Canadian Institutes of Health Research/Canada -- MOP77682/Canadian Institutes of Health Research/Canada -- N01 HC-15103/HC/NHLBI NIH HHS/ -- N01 HC-55222/HC/NHLBI NIH HHS/ -- N01 HC-95159/HC/NHLBI NIH HHS/ -- N01 HC-95169/HC/NHLBI NIH HHS/ -- N01-AG-1-2109/AG/NIA 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-HC-95160/HC/NHLBI NIH HHS/ -- N01-HC-95161/HC/NHLBI NIH HHS/ -- N01-HC-95162/HC/NHLBI NIH HHS/ -- N01-HC-95163/HC/NHLBI NIH HHS/ -- N01-HC-95164/HC/NHLBI NIH HHS/ -- N01-HC-95165/HC/NHLBI NIH HHS/ -- N01-HC-95166/HC/NHLBI NIH HHS/ -- N01-HC-95167/HC/NHLBI NIH HHS/ -- N01-HC-95168/HC/NHLBI NIH HHS/ -- N01-HD-1-3107/HD/NICHD NIH HHS/ -- N01AG6210/AG/NIA NIH HHS/ -- N01AG62101/AG/NIA NIH HHS/ -- N01AG62103/AG/NIA NIH HHS/ -- N02-HL-6-4278/HL/NHLBI NIH HHS/ -- P01CA055075/CA/NCI NIH HHS/ -- P01CA087969/CA/NCI NIH HHS/ -- P30 ES010126/ES/NIEHS NIH HHS/ -- P30ES007033/ES/NIEHS NIH HHS/ -- PG/02/128/British Heart Foundation/United Kingdom -- PG97012/British Heart Foundation/United Kingdom -- PG97027/British Heart Foundation/United Kingdom -- R01 AG017644-09S1/AG/NIA NIH HHS/ -- R01 AG18728/AG/NIA NIH HHS/ -- R01 DK072193/DK/NIDDK NIH HHS/ -- R01 DK078150/DK/NIDDK NIH HHS/ -- R01 HL073410/HL/NHLBI NIH HHS/ -- R01 HL085251/HL/NHLBI NIH HHS/ -- R01 HL086694/HL/NHLBI NIH HHS/ -- R01 HL086694-03/HL/NHLBI NIH HHS/ -- R01 HL086694-04A1/HL/NHLBI NIH HHS/ -- R01 HL086694-05/HL/NHLBI NIH HHS/ -- R01 HL087647/HL/NHLBI NIH HHS/ -- R01 HL087652/HL/NHLBI NIH HHS/ -- R01 HL088119/HL/NHLBI NIH HHS/ -- R01 NS39987/NS/NINDS NIH HHS/ -- R01 NS42733/NS/NINDS NIH HHS/ -- R01DK058845/DK/NIDDK NIH HHS/ -- R01DK066574/DK/NIDDK NIH HHS/ -- R01HL056931/HL/NHLBI NIH HHS/ -- R01HL060894/HL/NHLBI NIH HHS/ -- R01HL060919/HL/NHLBI NIH HHS/ -- R01HL06094/HL/NHLBI NIH HHS/ -- R01HL061019/HL/NHLBI NIH HHS/ -- R01HL071051/HL/NHLBI NIH HHS/ -- R01HL071205/HL/NHLBI NIH HHS/ -- R01HL071250/HL/NHLBI NIH HHS/ -- R01HL071251/HL/NHLBI NIH HHS/ -- R01HL071252/HL/NHLBI NIH HHS/ -- R01HL071258/HL/NHLBI NIH HHS/ -- R01HL071259/HL/NHLBI NIH HHS/ -- R01HL086694/HL/NHLBI NIH HHS/ -- R01HL087641/HL/NHLBI NIH HHS/ -- R01HL089650-02/HL/NHLBI NIH HHS/ -- R01HL59367/HL/NHLBI NIH HHS/ -- R03 TW007165/TW/FIC NIH HHS/ -- R37HL051021/HL/NHLBI NIH HHS/ -- RG/07/005/23633/British Heart Foundation/United Kingdom -- RG/07/008/23674/British Heart Foundation/United Kingdom -- RG/08/008/25291/British Heart Foundation/United Kingdom -- RG/08/013/25942/British Heart Foundation/United Kingdom -- RG/08/014/24067/British Heart Foundation/United Kingdom -- RG/98002/British Heart Foundation/United Kingdom -- RG08/01/British Heart Foundation/United Kingdom -- RR-024156/RR/NCRR NIH HHS/ -- RR20649/RR/NCRR NIH HHS/ -- S06GM008016-320107/GM/NIGMS NIH HHS/ -- S06GM008016-380111/GM/NIGMS NIH HHS/ -- SP/04/002/British Heart Foundation/United Kingdom -- SP/08/005/25115/British Heart Foundation/United Kingdom -- TW008288/TW/FIC NIH HHS/ -- TW05596/TW/FIC NIH HHS/ -- U01 DK062418/DK/NIDDK NIH HHS/ -- U01 GM074518-04/GM/NIGMS NIH HHS/ -- U01 HL054466/HL/NHLBI NIH HHS/ -- U01 HL054466-11/HL/NHLBI NIH HHS/ -- U01 HL054471/HL/NHLBI NIH HHS/ -- U01 HL054473/HL/NHLBI NIH HHS/ -- U01 HL054527/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL080295/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 NS069208/NS/NINDS NIH HHS/ -- U01 NS069208-01/NS/NINDS NIH HHS/ -- U01DE018903/DE/NIDCR NIH HHS/ -- U01DE01899/DE/NIDCR NIH HHS/ -- U01HG004399/HG/NHGRI NIH HHS/ -- U01HG004402/HG/NHGRI NIH HHS/ -- U01HG004415/HG/NHGRI NIH HHS/ -- U01HG004422/HG/NHGRI NIH HHS/ -- U01HG004423/HG/NHGRI NIH HHS/ -- U01HG004436/HG/NHGRI NIH HHS/ -- U01HG004438/HG/NHGRI NIH HHS/ -- U01HG004446/HG/NHGRI NIH HHS/ -- U01HG004726/HG/NHGRI NIH HHS/ -- U01HG004728/HG/NHGRI NIH HHS/ -- U01HG004729/HG/NHGRI NIH HHS/ -- U01HG004735/HG/NHGRI NIH HHS/ -- U01HG004738/HG/NHGRI NIH HHS/ -- U10 HL054512/HL/NHLBI NIH HHS/ -- U10HL054512/HL/NHLBI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- UL1RR025005/RR/NCRR NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2011 Sep 11;478(7367):103-9. doi: 10.1038/nature10405.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21909115" target="_blank"〉PubMed〈/a〉

Description: Arising from M. A. Nowak, C. E. Tarnita & E. O. Wilson 466, 1057-1062 (2010); Nowak et al. reply. Nowak et al. argue that inclusive fitness theory has been of little value in explaining the natural world, and that it has led to negligible progress in explaining the evolution of eusociality. However, we believe that their arguments are based upon a misunderstanding of evolutionary theory and a misrepresentation of the empirical literature. We will focus our comments on three general issues.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836173/" 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/PMC3836173/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Abbot, Patrick -- Abe, Jun -- Alcock, John -- Alizon, Samuel -- Alpedrinha, Joao A C -- Andersson, Malte -- Andre, Jean-Baptiste -- van Baalen, Minus -- Balloux, Francois -- Balshine, Sigal -- Barton, Nick -- Beukeboom, Leo W -- Biernaskie, Jay M -- Bilde, Trine -- Borgia, Gerald -- Breed, Michael -- Brown, Sam -- Bshary, Redouan -- Buckling, Angus -- Burley, Nancy T -- Burton-Chellew, Max N -- Cant, Michael A -- Chapuisat, Michel -- Charnov, Eric L -- Clutton-Brock, Tim -- Cockburn, Andrew -- Cole, Blaine J -- Colegrave, Nick -- Cosmides, Leda -- Couzin, Iain D -- Coyne, Jerry A -- Creel, Scott -- Crespi, Bernard -- Curry, Robert L -- Dall, Sasha R X -- Day, Troy -- Dickinson, Janis L -- Dugatkin, Lee Alan -- El Mouden, Claire -- Emlen, Stephen T -- Evans, Jay -- Ferriere, Regis -- Field, Jeremy -- Foitzik, Susanne -- Foster, Kevin -- Foster, William A -- Fox, Charles W -- Gadau, Juergen -- Gandon, Sylvain -- Gardner, Andy -- Gardner, Michael G -- Getty, Thomas -- Goodisman, Michael A D -- Grafen, Alan -- Grosberg, Rick -- Grozinger, Christina M -- Gouyon, Pierre-Henri -- Gwynne, Darryl -- Harvey, Paul H -- Hatchwell, Ben J -- Heinze, Jurgen -- Helantera, Heikki -- Helms, Ken R -- Hill, Kim -- Jiricny, Natalie -- Johnstone, Rufus A -- Kacelnik, Alex -- Kiers, E Toby -- Kokko, Hanna -- Komdeur, Jan -- Korb, Judith -- Kronauer, Daniel -- Kummerli, Rolf -- Lehmann, Laurent -- Linksvayer, Timothy A -- Lion, Sebastien -- Lyon, Bruce -- Marshall, James A R -- McElreath, Richard -- Michalakis, Yannis -- Michod, Richard E -- Mock, Douglas -- Monnin, Thibaud -- Montgomerie, Robert -- Moore, Allen J -- Mueller, Ulrich G -- Noe, Ronald -- Okasha, Samir -- Pamilo, Pekka -- Parker, Geoff A -- Pedersen, Jes S -- Pen, Ido -- Pfennig, David -- Queller, David C -- Rankin, Daniel J -- Reece, Sarah E -- Reeve, Hudson K -- Reuter, Max -- Roberts, Gilbert -- Robson, Simon K A -- Roze, Denis -- Rousset, Francois -- Rueppell, Olav -- Sachs, Joel L -- Santorelli, Lorenzo -- Schmid-Hempel, Paul -- Schwarz, Michael P -- Scott-Phillips, Tom -- Shellmann-Sherman, Janet -- Sherman, Paul W -- Shuker, David M -- Smith, Jeff -- Spagna, Joseph C -- Strassmann, Beverly -- Suarez, Andrew V -- Sundstrom, Liselotte -- Taborsky, Michael -- Taylor, Peter -- Thompson, Graham -- Tooby, John -- Tsutsui, Neil D -- Tsuji, Kazuki -- Turillazzi, Stefano -- Ubeda, Francisco -- Vargo, Edward L -- Voelkl, Bernard -- Wenseleers, Tom -- West, Stuart A -- West-Eberhard, Mary Jane -- Westneat, David F -- Wiernasz, Diane C -- Wild, Geoff -- Wrangham, Richard -- Young, Andrew J -- Zeh, David W -- Zeh, Jeanne A -- Zink, Andrew -- BB/H022716/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2011 Mar 24;471(7339):E1-4; author reply E9-10. doi: 10.1038/nature09831.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21430721" target="_blank"〉PubMed〈/a〉

Description: Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) 〈/= 18.5 kg per m(2) in adults and 〈/= -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a approximately 600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637175/" 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/PMC3637175/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacquemont, Sebastien -- Reymond, Alexandre -- Zufferey, Flore -- Harewood, Louise -- Walters, Robin G -- Kutalik, Zoltan -- Martinet, Danielle -- Shen, Yiping -- Valsesia, Armand -- Beckmann, Noam D -- Thorleifsson, Gudmar -- Belfiore, Marco -- Bouquillon, Sonia -- Campion, Dominique -- de Leeuw, Nicole -- de Vries, Bert B A -- Esko, Tonu -- Fernandez, Bridget A -- Fernandez-Aranda, Fernando -- Fernandez-Real, Jose Manuel -- Gratacos, Monica -- Guilmatre, Audrey -- Hoyer, Juliane -- Jarvelin, Marjo-Riitta -- Kooy, R Frank -- Kurg, Ants -- Le Caignec, Cedric -- Mannik, Katrin -- Platt, Orah S -- Sanlaville, Damien -- Van Haelst, Mieke M -- Villatoro Gomez, Sergi -- Walha, Faida -- Wu, Bai-Lin -- Yu, Yongguo -- Aboura, Azzedine -- Addor, Marie-Claude -- Alembik, Yves -- Antonarakis, Stylianos E -- Arveiler, Benoit -- Barth, Magalie -- Bednarek, Nathalie -- Bena, Frederique -- Bergmann, Sven -- Beri, Mylene -- Bernardini, Laura -- Blaumeiser, Bettina -- Bonneau, Dominique -- Bottani, Armand -- Boute, Odile -- Brunner, Han G -- Cailley, Dorothee -- Callier, Patrick -- Chiesa, Jean -- Chrast, Jacqueline -- Coin, Lachlan -- Coutton, Charles -- Cuisset, Jean-Marie -- Cuvellier, Jean-Christophe -- David, Albert -- de Freminville, Benedicte -- Delobel, Bruno -- Delrue, Marie-Ange -- Demeer, Benedicte -- Descamps, Dominique -- Didelot, Gerard -- Dieterich, Klaus -- Disciglio, Vittoria -- Doco-Fenzy, Martine -- Drunat, Severine -- Duban-Bedu, Benedicte -- Dubourg, Christele -- El-Sayed Moustafa, Julia S -- Elliott, Paul -- Faas, Brigitte H W -- Faivre, Laurence -- Faudet, Anne -- Fellmann, Florence -- Ferrarini, Alessandra -- Fisher, Richard -- Flori, Elisabeth -- Forer, Lukas -- Gaillard, Dominique -- Gerard, Marion -- Gieger, Christian -- Gimelli, Stefania -- Gimelli, Giorgio -- Grabe, Hans J -- Guichet, Agnes -- Guillin, Olivier -- Hartikainen, Anna-Liisa -- Heron, Delphine -- Hippolyte, Loyse -- Holder, Muriel -- Homuth, Georg -- Isidor, Bertrand -- Jaillard, Sylvie -- Jaros, Zdenek -- Jimenez-Murcia, Susana -- Helas, Geraldine Joly -- Jonveaux, Philippe -- Kaksonen, Satu -- Keren, Boris -- Kloss-Brandstatter, Anita -- Knoers, Nine V A M -- Koolen, David A -- Kroisel, Peter M -- Kronenberg, Florian -- Labalme, Audrey -- Landais, Emilie -- Lapi, Elisabetta -- Layet, Valerie -- Legallic, Solenn -- Leheup, Bruno -- Leube, Barbara -- Lewis, Suzanne -- Lucas, Josette -- MacDermot, Kay D -- Magnusson, Pall -- Marshall, Christian -- Mathieu-Dramard, Michele -- McCarthy, Mark I -- Meitinger, Thomas -- Mencarelli, Maria Antonietta -- Merla, Giuseppe -- Moerman, Alexandre -- Mooser, Vincent -- Morice-Picard, Fanny -- Mucciolo, Mafalda -- Nauck, Matthias -- Ndiaye, Ndeye Coumba -- Nordgren, Ann -- Pasquier, Laurent -- Petit, Florence -- Pfundt, Rolph -- Plessis, Ghislaine -- Rajcan-Separovic, Evica -- Ramelli, Gian Paolo -- Rauch, Anita -- Ravazzolo, Roberto -- Reis, Andre -- Renieri, Alessandra -- Richart, Cristobal -- Ried, Janina S -- Rieubland, Claudine -- Roberts, Wendy -- Roetzer, Katharina M -- Rooryck, Caroline -- Rossi, Massimiliano -- Saemundsen, Evald -- Satre, Veronique -- Schurmann, Claudia -- Sigurdsson, Engilbert -- Stavropoulos, Dimitri J -- Stefansson, Hreinn -- Tengstrom, Carola -- Thorsteinsdottir, Unnur -- Tinahones, Francisco J -- Touraine, Renaud -- Vallee, Louis -- van Binsbergen, Ellen -- Van der Aa, Nathalie -- Vincent-Delorme, Catherine -- Visvikis-Siest, Sophie -- Vollenweider, Peter -- Volzke, Henry -- Vulto-van Silfhout, Anneke T -- Waeber, Gerard -- Wallgren-Pettersson, Carina -- Witwicki, Robert M -- Zwolinksi, Simon -- Andrieux, Joris -- Estivill, Xavier -- Gusella, James F -- Gustafsson, Omar -- Metspalu, Andres -- Scherer, Stephen W -- Stefansson, Kari -- Blakemore, Alexandra I F -- Beckmann, Jacques S -- Froguel, Philippe -- 090532/Wellcome Trust/United Kingdom -- 1RL1MH083268-01/MH/NIMH NIH HHS/ -- 5R01HL087679-02/HL/NHLBI NIH HHS/ -- 5R01MH63706:02/MH/NIMH NIH HHS/ -- AS2173/Autism Speaks/ -- G0500539/Medical Research Council/United Kingdom -- G0600705/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- GM061354/GM/NIGMS NIH HHS/ -- MH071425/MH/NIMH NIH HHS/ -- MOP 74502/Canadian Institutes of Health Research/Canada -- Wellcome Trust/United Kingdom -- England -- Nature. 2011 Aug 31;478(7367):97-102. doi: 10.1038/nature10406.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21881559" target="_blank"〉PubMed〈/a〉

Description: Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335296/" 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/PMC3335296/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gieger, Christian -- Radhakrishnan, Aparna -- Cvejic, Ana -- Tang, Weihong -- Porcu, Eleonora -- Pistis, Giorgio -- Serbanovic-Canic, Jovana -- Elling, Ulrich -- Goodall, Alison H -- Labrune, Yann -- Lopez, Lorna M -- Magi, Reedik -- Meacham, Stuart -- Okada, Yukinori -- Pirastu, Nicola -- Sorice, Rossella -- Teumer, Alexander -- Voss, Katrin -- Zhang, Weihua -- Ramirez-Solis, Ramiro -- Bis, Joshua C -- Ellinghaus, David -- Gogele, Martin -- Hottenga, Jouke-Jan -- Langenberg, Claudia -- Kovacs, Peter -- O'Reilly, Paul F -- Shin, So-Youn -- Esko, Tonu -- Hartiala, Jaana -- Kanoni, Stavroula -- Murgia, Federico -- Parsa, Afshin -- Stephens, Jonathan -- van der Harst, Pim -- Ellen van der Schoot, C -- Allayee, Hooman -- Attwood, Antony -- Balkau, Beverley -- Bastardot, Francois -- Basu, Saonli -- Baumeister, Sebastian E -- Biino, Ginevra -- Bomba, Lorenzo -- Bonnefond, Amelie -- Cambien, Francois -- Chambers, John C -- Cucca, Francesco -- D'Adamo, Pio -- Davies, Gail -- de Boer, Rudolf A -- de Geus, Eco J C -- Doring, Angela -- Elliott, Paul -- Erdmann, Jeanette -- Evans, David M -- Falchi, Mario -- Feng, Wei -- Folsom, Aaron R -- Frazer, Ian H -- Gibson, Quince D -- Glazer, Nicole L -- Hammond, Chris -- Hartikainen, Anna-Liisa -- Heckbert, Susan R -- Hengstenberg, Christian -- Hersch, Micha -- Illig, Thomas -- Loos, Ruth J F -- Jolley, Jennifer -- Khaw, Kay Tee -- Kuhnel, Brigitte -- Kyrtsonis, Marie-Christine -- Lagou, Vasiliki -- Lloyd-Jones, Heather -- Lumley, Thomas -- Mangino, Massimo -- Maschio, Andrea -- Mateo Leach, Irene -- McKnight, Barbara -- Memari, Yasin -- Mitchell, Braxton D -- Montgomery, Grant W -- Nakamura, Yusuke -- Nauck, Matthias -- Navis, Gerjan -- Nothlings, Ute -- Nolte, Ilja M -- Porteous, David J -- Pouta, Anneli -- Pramstaller, Peter P -- Pullat, Janne -- Ring, Susan M -- Rotter, Jerome I -- Ruggiero, Daniela -- Ruokonen, Aimo -- Sala, Cinzia -- Samani, Nilesh J -- Sambrook, Jennifer -- Schlessinger, David -- Schreiber, Stefan -- Schunkert, Heribert -- Scott, James -- Smith, Nicholas L -- Snieder, Harold -- Starr, John M -- Stumvoll, Michael -- Takahashi, Atsushi -- Tang, W H Wilson -- Taylor, Kent -- Tenesa, Albert -- Lay Thein, Swee -- Tonjes, Anke -- Uda, Manuela -- Ulivi, Sheila -- van Veldhuisen, Dirk J -- Visscher, Peter M -- Volker, Uwe -- Wichmann, H-Erich -- Wiggins, Kerri L -- Willemsen, Gonneke -- Yang, Tsun-Po -- Hua Zhao, Jing -- Zitting, Paavo -- Bradley, John R -- Dedoussis, George V -- Gasparini, Paolo -- Hazen, Stanley L -- Metspalu, Andres -- Pirastu, Mario -- Shuldiner, Alan R -- Joost van Pelt, L -- Zwaginga, Jaap-Jan -- Boomsma, Dorret I -- Deary, Ian J -- Franke, Andre -- Froguel, Philippe -- Ganesh, Santhi K -- Jarvelin, Marjo-Riitta -- Martin, Nicholas G -- Meisinger, Christa -- Psaty, Bruce M -- Spector, Timothy D -- Wareham, Nicholas J -- Akkerman, Jan-Willem N -- Ciullo, Marina -- Deloukas, Panos -- Greinacher, Andreas -- Jupe, Steve -- Kamatani, Naoyuki -- Khadake, Jyoti -- Kooner, Jaspal S -- Penninger, Josef -- Prokopenko, Inga -- Stemple, Derek -- Toniolo, Daniela -- Wernisch, Lorenz -- Sanna, Serena -- Hicks, Andrew A -- Rendon, Augusto -- Ferreira, Manuel A -- Ouwehand, Willem H -- Soranzo, Nicole -- 092731/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- BB/F019394/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- CZB/4/505/Chief Scientist Office/United Kingdom -- ETM/55/Chief Scientist Office/United Kingdom -- G0000111/Medical Research Council/United Kingdom -- G0601966/Medical Research Council/United Kingdom -- G0700704/Medical Research Council/United Kingdom -- G0700931/Medical Research Council/United Kingdom -- G0701120/Medical Research Council/United Kingdom -- G0701863/Medical Research Council/United Kingdom -- G0801056/Medical Research Council/United Kingdom -- G1000143/Medical Research Council/United Kingdom -- K12 RR023250/RR/NCRR NIH HHS/ -- K12 RR023250-05/RR/NCRR NIH HHS/ -- M01 RR016500/RR/NCRR NIH HHS/ -- M01 RR016500-08/RR/NCRR NIH HHS/ -- MC_U105260799/Medical Research Council/United Kingdom -- MC_U106179471/Medical Research Council/United Kingdom -- MC_U106188470/Medical Research Council/United Kingdom -- N01 HC055015/HC/NHLBI NIH HHS/ -- N01 HC055016/HC/NHLBI NIH HHS/ -- N01 HC055018/HC/NHLBI NIH HHS/ -- N01 HC055019/HC/NHLBI NIH HHS/ -- N01 HC055020/HC/NHLBI NIH HHS/ -- N01 HC055021/HC/NHLBI NIH HHS/ -- N01 HC055022/HC/NHLBI NIH HHS/ -- N01 HC085079/HC/NHLBI NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL076491-09/HL/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- P01 HL098055-03/HL/NHLBI NIH HHS/ -- P30 DK072488/DK/NIDDK NIH HHS/ -- P30 DK072488-08/DK/NIDDK NIH HHS/ -- P41 HG003751/HG/NHGRI NIH HHS/ -- R01 AG018728/AG/NIA NIH HHS/ -- R01 AG018728-05S1/AG/NIA NIH HHS/ -- R01 GM053275/GM/NIGMS NIH HHS/ -- R01 GM053275-14/GM/NIGMS NIH HHS/ -- R01 HD042157/HD/NICHD NIH HHS/ -- R01 HD042157-01A1/HD/NICHD NIH HHS/ -- R01 HL059367/HL/NHLBI NIH HHS/ -- R01 HL059367-11/HL/NHLBI NIH HHS/ -- R01 HL068986/HL/NHLBI NIH HHS/ -- R01 HL068986-06/HL/NHLBI NIH HHS/ -- R01 HL073410/HL/NHLBI NIH HHS/ -- R01 HL073410-08/HL/NHLBI NIH HHS/ -- R01 HL085251/HL/NHLBI NIH HHS/ -- R01 HL085251-04/HL/NHLBI NIH HHS/ -- R01 HL086694/HL/NHLBI NIH HHS/ -- R01 HL086694-05/HL/NHLBI NIH HHS/ -- R01 HL087641/HL/NHLBI NIH HHS/ -- R01 HL087641-03/HL/NHLBI NIH HHS/ -- R01 HL087679-03/HL/NHLBI NIH HHS/ -- R01 HL088119/HL/NHLBI NIH HHS/ -- R01 HL088119-04/HL/NHLBI NIH HHS/ -- R01 HL103866/HL/NHLBI NIH HHS/ -- R01 HL103866-03/HL/NHLBI NIH HHS/ -- R01 HL105756/HL/NHLBI NIH HHS/ -- RG/09/012/28096/British Heart Foundation/United Kingdom -- RL1 MH083268/MH/NIMH NIH HHS/ -- RL1 MH083268-05/MH/NIMH NIH HHS/ -- U01 GM074518/GM/NIGMS NIH HHS/ -- U01 GM074518-04/GM/NIGMS NIH HHS/ -- U01 HL072515/HL/NHLBI NIH HHS/ -- U01 HL072515-06/HL/NHLBI NIH HHS/ -- U01 HL084756/HL/NHLBI NIH HHS/ -- U01 HL084756-03/HL/NHLBI NIH HHS/ -- U54 RR020278/RR/NCRR NIH HHS/ -- U54 RR020278-06/RR/NCRR NIH HHS/ -- UL1 RR025005/RR/NCRR NIH HHS/ -- UL1 RR025005-05/RR/NCRR NIH HHS/ -- WT077037/Z/05/Z/Wellcome Trust/United Kingdom -- WT077047/Z/05/Z/Wellcome Trust/United Kingdom -- WT082597/Z/07/Z/Wellcome Trust/United Kingdom -- England -- Nature. 2011 Nov 30;480(7376):201-8. doi: 10.1038/nature10659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Genetic Epidemiology, Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Ingolstadter Landstr 1, 85764 Neuherberg, Germany. christian.gieger@helmholtz-muenchen.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22139419" target="_blank"〉PubMed〈/a〉

Description: Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182531/" 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/PMC3182531/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Multiple Sclerosis Genetics Consortium -- Wellcome Trust Case Control Consortium 2 -- Sawcer, Stephen -- Hellenthal, Garrett -- Pirinen, Matti -- Spencer, Chris C A -- Patsopoulos, Nikolaos A -- Moutsianas, Loukas -- Dilthey, Alexander -- Su, Zhan -- Freeman, Colin -- Hunt, Sarah E -- Edkins, Sarah -- Gray, Emma -- Booth, David R -- Potter, Simon C -- Goris, An -- Band, Gavin -- Oturai, Annette Bang -- Strange, Amy -- Saarela, Janna -- Bellenguez, Celine -- Fontaine, Bertrand -- Gillman, Matthew -- Hemmer, Bernhard -- Gwilliam, Rhian -- Zipp, Frauke -- Jayakumar, Alagurevathi -- Martin, Roland -- Leslie, Stephen -- Hawkins, Stanley -- Giannoulatou, Eleni -- D'alfonso, Sandra -- Blackburn, Hannah -- Martinelli Boneschi, Filippo -- Liddle, Jennifer -- Harbo, Hanne F -- Perez, Marc L -- Spurkland, Anne -- Waller, Matthew J -- Mycko, Marcin P -- Ricketts, Michelle -- Comabella, Manuel -- Hammond, Naomi -- Kockum, Ingrid -- McCann, Owen T -- Ban, Maria -- Whittaker, Pamela -- Kemppinen, Anu -- Weston, Paul -- Hawkins, Clive -- Widaa, Sara -- Zajicek, John -- Dronov, Serge -- Robertson, Neil -- Bumpstead, Suzannah J -- Barcellos, Lisa F -- Ravindrarajah, Rathi -- Abraham, Roby -- Alfredsson, Lars -- Ardlie, Kristin -- Aubin, Cristin -- Baker, Amie -- Baker, Katharine -- Baranzini, Sergio E -- Bergamaschi, Laura -- Bergamaschi, Roberto -- Bernstein, Allan -- Berthele, Achim -- Boggild, Mike -- Bradfield, Jonathan P -- Brassat, David -- Broadley, Simon A -- Buck, Dorothea -- Butzkueven, Helmut -- Capra, Ruggero -- Carroll, William M -- Cavalla, Paola -- Celius, Elisabeth G -- Cepok, Sabine -- Chiavacci, Rosetta -- Clerget-Darpoux, Francoise -- Clysters, Katleen -- Comi, Giancarlo -- Cossburn, Mark -- Cournu-Rebeix, Isabelle -- Cox, Mathew B -- Cozen, Wendy -- Cree, Bruce A C -- Cross, Anne H -- Cusi, Daniele -- Daly, Mark J -- Davis, Emma -- de Bakker, Paul I W -- Debouverie, Marc -- D'hooghe, Marie Beatrice -- Dixon, Katherine -- Dobosi, Rita -- Dubois, Benedicte -- Ellinghaus, David -- Elovaara, Irina -- Esposito, Federica -- Fontenille, Claire -- Foote, Simon -- Franke, Andre -- Galimberti, Daniela -- Ghezzi, Angelo -- Glessner, Joseph -- Gomez, Refujia -- Gout, Olivier -- Graham, Colin -- Grant, Struan F A -- Guerini, Franca Rosa -- Hakonarson, Hakon -- Hall, Per -- Hamsten, Anders -- Hartung, Hans-Peter -- Heard, Rob N -- Heath, Simon -- Hobart, Jeremy -- Hoshi, Muna -- Infante-Duarte, Carmen -- Ingram, Gillian -- Ingram, Wendy -- Islam, Talat -- Jagodic, Maja -- Kabesch, Michael -- Kermode, Allan G -- Kilpatrick, Trevor J -- Kim, Cecilia -- Klopp, Norman -- Koivisto, Keijo -- Larsson, Malin -- Lathrop, Mark -- Lechner-Scott, Jeannette S -- Leone, Maurizio A -- Leppa, Virpi -- Liljedahl, Ulrika -- Bomfim, Izaura Lima -- Lincoln, Robin R -- Link, Jenny -- Liu, Jianjun -- Lorentzen, Aslaug R -- Lupoli, Sara -- Macciardi, Fabio -- Mack, Thomas -- Marriott, Mark -- Martinelli, Vittorio -- Mason, Deborah -- McCauley, Jacob L -- Mentch, Frank -- Mero, Inger-Lise -- Mihalova, Tania -- Montalban, Xavier -- Mottershead, John -- Myhr, Kjell-Morten -- Naldi, Paola -- Ollier, William -- Page, Alison -- Palotie, Aarno -- Pelletier, Jean -- Piccio, Laura -- Pickersgill, Trevor -- Piehl, Fredrik -- Pobywajlo, Susan -- Quach, Hong L -- Ramsay, Patricia P -- Reunanen, Mauri -- Reynolds, Richard -- Rioux, John D -- Rodegher, Mariaemma -- Roesner, Sabine -- Rubio, Justin P -- Ruckert, Ina-Maria -- Salvetti, Marco -- Salvi, Erika -- Santaniello, Adam -- Schaefer, Catherine A -- Schreiber, Stefan -- Schulze, Christian -- Scott, Rodney J -- Sellebjerg, Finn -- Selmaj, Krzysztof W -- Sexton, David -- Shen, Ling -- Simms-Acuna, Brigid -- Skidmore, Sheila -- Sleiman, Patrick M A -- Smestad, Cathrine -- Sorensen, Per Soelberg -- Sondergaard, Helle Bach -- Stankovich, Jim -- Strange, Richard C -- Sulonen, Anna-Maija -- Sundqvist, Emilie -- Syvanen, Ann-Christine -- Taddeo, Francesca -- Taylor, Bruce -- Blackwell, Jenefer M -- Tienari, Pentti -- Bramon, Elvira -- Tourbah, Ayman -- Brown, Matthew A -- Tronczynska, Ewa -- Casas, Juan P -- Tubridy, Niall -- Corvin, Aiden -- Vickery, Jane -- Jankowski, Janusz -- Villoslada, Pablo -- Markus, Hugh S -- Wang, Kai -- Mathew, Christopher G -- Wason, James -- Palmer, Colin N A -- Wichmann, H-Erich -- Plomin, Robert -- Willoughby, Ernest -- Rautanen, Anna -- Winkelmann, Juliane -- Wittig, Michael -- Trembath, Richard C -- Yaouanq, Jacqueline -- Viswanathan, Ananth C -- Zhang, Haitao -- Wood, Nicholas W -- Zuvich, Rebecca -- Deloukas, Panos -- Langford, Cordelia -- Duncanson, Audrey -- Oksenberg, Jorge R -- Pericak-Vance, Margaret A -- Haines, Jonathan L -- Olsson, Tomas -- Hillert, Jan -- Ivinson, Adrian J -- De Jager, Philip L -- Peltonen, Leena -- Stewart, Graeme J -- Hafler, David A -- Hauser, Stephen L -- McVean, Gil -- Donnelly, Peter -- Compston, Alastair -- 068545/Z/02/Wellcome Trust/United Kingdom -- 075491/Z/04/Z/Wellcome Trust/United Kingdom -- 084702/Wellcome Trust/United Kingdom -- 085475/Wellcome Trust/United Kingdom -- 085475/B/08/Z/Wellcome Trust/United Kingdom -- 085475/Z/08/Z/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 898/Multiple Sclerosis Society/United Kingdom -- AI076544/AI/NIAID NIH HHS/ -- CA104021/CA/NCI NIH HHS/ -- G0100594/Medical Research Council/United Kingdom -- G0400017/Medical Research Council/United Kingdom -- G0700061/Medical Research Council/United Kingdom -- G0901310/Medical Research Council/United Kingdom -- G0901461/Medical Research Council/United Kingdom -- G19/2/Medical Research Council/United Kingdom -- K23N/S048869/PHS HHS/ -- NS032830/NS/NINDS NIH HHS/ -- NS049477/NS/NINDS NIH HHS/ -- NS049510/NS/NINDS NIH HHS/ -- NS067305/NS/NINDS NIH HHS/ -- NS19142/NS/NINDS NIH HHS/ -- NS26799/NS/NINDS NIH HHS/ -- NS43559/NS/NINDS NIH HHS/ -- PDA/02/06/016/Department of Health/United Kingdom -- R01 NS026799/NS/NINDS NIH HHS/ -- R01 NS049477/NS/NINDS NIH HHS/ -- R01 NS049477-06A1/NS/NINDS NIH HHS/ -- RR020092/RR/NCRR NIH HHS/ -- RR024992/RR/NCRR NIH HHS/ -- UL1 TR000448/TR/NCATS NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Aug 10;476(7359):214-9. doi: 10.1038/nature10251.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21833088" target="_blank"〉PubMed〈/a〉

Description: The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering approximately 4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for approximately 60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3207357/" 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/PMC3207357/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lindblad-Toh, Kerstin -- Garber, Manuel -- Zuk, Or -- Lin, Michael F -- Parker, Brian J -- Washietl, Stefan -- Kheradpour, Pouya -- Ernst, Jason -- Jordan, Gregory -- Mauceli, Evan -- Ward, Lucas D -- Lowe, Craig B -- Holloway, Alisha K -- Clamp, Michele -- Gnerre, Sante -- Alfoldi, Jessica -- Beal, Kathryn -- Chang, Jean -- Clawson, Hiram -- Cuff, James -- Di Palma, Federica -- Fitzgerald, Stephen -- Flicek, Paul -- Guttman, Mitchell -- Hubisz, Melissa J -- Jaffe, David B -- Jungreis, Irwin -- Kent, W James -- Kostka, Dennis -- Lara, Marcia -- Martins, Andre L -- Massingham, Tim -- Moltke, Ida -- Raney, Brian J -- Rasmussen, Matthew D -- Robinson, Jim -- Stark, Alexander -- Vilella, Albert J -- Wen, Jiayu -- Xie, Xiaohui -- Zody, Michael C -- Broad Institute Sequencing Platform and Whole Genome Assembly Team -- Baldwin, Jen -- Bloom, Toby -- Chin, Chee Whye -- Heiman, Dave -- Nicol, Robert -- Nusbaum, Chad -- Young, Sarah -- Wilkinson, Jane -- Worley, Kim C -- Kovar, Christie L -- Muzny, Donna M -- Gibbs, Richard A -- Baylor College of Medicine Human Genome Sequencing Center Sequencing Team -- Cree, Andrew -- Dihn, Huyen H -- Fowler, Gerald -- Jhangiani, Shalili -- Joshi, Vandita -- Lee, Sandra -- Lewis, Lora R -- Nazareth, Lynne V -- Okwuonu, Geoffrey -- Santibanez, Jireh -- Warren, Wesley C -- Mardis, Elaine R -- Weinstock, George M -- Wilson, Richard K -- Genome Institute at Washington University -- Delehaunty, Kim -- Dooling, David -- Fronik, Catrina -- Fulton, Lucinda -- Fulton, Bob -- Graves, Tina -- Minx, Patrick -- Sodergren, Erica -- Birney, Ewan -- Margulies, Elliott H -- Herrero, Javier -- Green, Eric D -- Haussler, David -- Siepel, Adam -- Goldman, Nick -- Pollard, Katherine S -- Pedersen, Jakob S -- Lander, Eric S -- Kellis, Manolis -- 095908/Wellcome Trust/United Kingdom -- GM82901/GM/NIGMS NIH HHS/ -- R01 HG003474/HG/NHGRI NIH HHS/ -- R01 HG004037/HG/NHGRI NIH HHS/ -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-09/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Oct 12;478(7370):476-82. doi: 10.1038/nature10530.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. kersli@broadinstitute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21993624" target="_blank"〉PubMed〈/a〉

Description: The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse-more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3184186/" 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/PMC3184186/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alfoldi, Jessica -- Di Palma, Federica -- Grabherr, Manfred -- Williams, Christina -- Kong, Lesheng -- Mauceli, Evan -- Russell, Pamela -- Lowe, Craig B -- Glor, Richard E -- Jaffe, Jacob D -- Ray, David A -- Boissinot, Stephane -- Shedlock, Andrew M -- Botka, Christopher -- Castoe, Todd A -- Colbourne, John K -- Fujita, Matthew K -- Moreno, Ricardo Godinez -- ten Hallers, Boudewijn F -- Haussler, David -- Heger, Andreas -- Heiman, David -- Janes, Daniel E -- Johnson, Jeremy -- de Jong, Pieter J -- Koriabine, Maxim Y -- Lara, Marcia -- Novick, Peter A -- Organ, Chris L -- Peach, Sally E -- Poe, Steven -- Pollock, David D -- de Queiroz, Kevin -- Sanger, Thomas -- Searle, Steve -- Smith, Jeremy D -- Smith, Zachary -- Swofford, Ross -- Turner-Maier, Jason -- Wade, Juli -- Young, Sarah -- Zadissa, Amonida -- Edwards, Scott V -- Glenn, Travis C -- Schneider, Christopher J -- Losos, Jonathan B -- Lander, Eric S -- Breen, Matthew -- Ponting, Chris P -- Lindblad-Toh, Kerstin -- BB/F007590/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- MC_U137761446/Medical Research Council/United Kingdom -- U54 HG003067/HG/NHGRI NIH HHS/ -- U54 HG003067-08/HG/NHGRI NIH HHS/ -- England -- Nature. 2011 Aug 31;477(7366):587-91. doi: 10.1038/nature10390.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA. jalfoldi@broadinstitute.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21881562" target="_blank"〉PubMed〈/a〉

Description: Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070744/" 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/PMC4070744/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lorenzen, Eline D -- Nogues-Bravo, David -- Orlando, Ludovic -- Weinstock, Jaco -- Binladen, Jonas -- Marske, Katharine A -- Ugan, Andrew -- Borregaard, Michael K -- Gilbert, M Thomas P -- Nielsen, Rasmus -- Ho, Simon Y W -- Goebel, Ted -- Graf, Kelly E -- Byers, David -- Stenderup, Jesper T -- Rasmussen, Morten -- Campos, Paula F -- Leonard, Jennifer A -- Koepfli, Klaus-Peter -- Froese, Duane -- Zazula, Grant -- Stafford, Thomas W Jr -- Aaris-Sorensen, Kim -- Batra, Persaram -- Haywood, Alan M -- Singarayer, Joy S -- Valdes, Paul J -- Boeskorov, Gennady -- Burns, James A -- Davydov, Sergey P -- Haile, James -- Jenkins, Dennis L -- Kosintsev, Pavel -- Kuznetsova, Tatyana -- Lai, Xulong -- Martin, Larry D -- McDonald, H Gregory -- Mol, Dick -- Meldgaard, Morten -- Munch, Kasper -- Stephan, Elisabeth -- Sablin, Mikhail -- Sommer, Robert S -- Sipko, Taras -- Scott, Eric -- Suchard, Marc A -- Tikhonov, Alexei -- Willerslev, Rane -- Wayne, Robert K -- Cooper, Alan -- Hofreiter, Michael -- Sher, Andrei -- Shapiro, Beth -- Rahbek, Carsten -- Willerslev, Eske -- R01 HG003229/HG/NHGRI NIH HHS/ -- England -- Nature. 2011 Nov 2;479(7373):359-64. doi: 10.1038/nature10574.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for GeoGenetics, University of Copenhagen, Oster Voldgade 5-7, DK-1350 Copenhagen K, Denmark.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22048313" target="_blank"〉PubMed〈/a〉

Description: Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210554/" 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/PMC3210554/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morin, Ryan D -- Mendez-Lago, Maria -- Mungall, Andrew J -- Goya, Rodrigo -- Mungall, Karen L -- Corbett, Richard D -- Johnson, Nathalie A -- Severson, Tesa M -- Chiu, Readman -- Field, Matthew -- Jackman, Shaun -- Krzywinski, Martin -- Scott, David W -- Trinh, Diane L -- Tamura-Wells, Jessica -- Li, Sa -- Firme, Marlo R -- Rogic, Sanja -- Griffith, Malachi -- Chan, Susanna -- Yakovenko, Oleksandr -- Meyer, Irmtraud M -- Zhao, Eric Y -- Smailus, Duane -- Moksa, Michelle -- Chittaranjan, Suganthi -- Rimsza, Lisa -- Brooks-Wilson, Angela -- Spinelli, John J -- Ben-Neriah, Susana -- Meissner, Barbara -- Woolcock, Bruce -- Boyle, Merrill -- McDonald, Helen -- Tam, Angela -- Zhao, Yongjun -- Delaney, Allen -- Zeng, Thomas -- Tse, Kane -- Butterfield, Yaron -- Birol, Inanc -- Holt, Rob -- Schein, Jacqueline -- Horsman, Douglas E -- Moore, Richard -- Jones, Steven J M -- Connors, Joseph M -- Hirst, Martin -- Gascoyne, Randy D -- Marra, Marco A -- 1U01CA114778/CA/NCI NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- P50CA130805-01/CA/NCI NIH HHS/ -- TGT-53912/Canadian Institutes of Health Research/Canada -- U24 CA143866/CA/NCI NIH HHS/ -- U24 CA143866-01/CA/NCI NIH HHS/ -- U24 CA143866-02/CA/NCI NIH HHS/ -- U24 CA143866-03/CA/NCI NIH HHS/ -- England -- Nature. 2011 Jul 27;476(7360):298-303. doi: 10.1038/nature10351.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21796119" target="_blank"〉PubMed〈/a〉

Description: 'Orang-utan' is derived from a Malay term meaning 'man of the forest' and aptly describes the southeast Asian great apes native to Sumatra and Borneo. The orang-utan species, Pongo abelii (Sumatran) and Pongo pygmaeus (Bornean), are the most phylogenetically distant great apes from humans, thereby providing an informative perspective on hominid evolution. Here we present a Sumatran orang-utan draft genome assembly and short read sequence data from five Sumatran and five Bornean orang-utan genomes. Our analyses reveal that, compared to other primates, the orang-utan genome has many unique features. Structural evolution of the orang-utan genome has proceeded much more slowly than other great apes, evidenced by fewer rearrangements, less segmental duplication, a lower rate of gene family turnover and surprisingly quiescent Alu repeats, which have played a major role in restructuring other primate genomes. We also describe a primate polymorphic neocentromere, found in both Pongo species, emphasizing the gradual evolution of orang-utan genome structure. Orang-utans have extremely low energy usage for a eutherian mammal, far lower than their hominid relatives. Adding their genome to the repertoire of sequenced primates illuminates new signals of positive selection in several pathways including glycolipid metabolism. From the population perspective, both Pongo species are deeply diverse; however, Sumatran individuals possess greater diversity than their Bornean counterparts, and more species-specific variation. Our estimate of Bornean/Sumatran speciation time, 400,000 years ago, is more recent than most previous studies and underscores the complexity of the orang-utan speciation process. Despite a smaller modern census population size, the Sumatran effective population size (N(e)) expanded exponentially relative to the ancestral N(e) after the split, while Bornean N(e) declined over the same period. Overall, the resources and analyses presented here offer new opportunities in evolutionary genomics, insights into hominid biology, and an extensive database of variation for conservation efforts.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060778/" 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/PMC3060778/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Locke, Devin P -- Hillier, LaDeana W -- Warren, Wesley C -- Worley, Kim C -- Nazareth, Lynne V -- Muzny, Donna M -- Yang, Shiaw-Pyng -- Wang, Zhengyuan -- Chinwalla, Asif T -- Minx, Pat -- Mitreva, Makedonka -- Cook, Lisa -- Delehaunty, Kim D -- Fronick, Catrina -- Schmidt, Heather -- Fulton, Lucinda A -- Fulton, Robert S -- Nelson, Joanne O -- Magrini, Vincent -- Pohl, Craig -- Graves, Tina A -- Markovic, Chris -- Cree, Andy -- Dinh, Huyen H -- Hume, Jennifer -- Kovar, Christie L -- Fowler, Gerald R -- Lunter, Gerton -- Meader, Stephen -- Heger, Andreas -- Ponting, Chris P -- Marques-Bonet, Tomas -- Alkan, Can -- Chen, Lin -- Cheng, Ze -- Kidd, Jeffrey M -- Eichler, Evan E -- White, Simon -- Searle, Stephen -- Vilella, Albert J -- Chen, Yuan -- Flicek, Paul -- Ma, Jian -- Raney, Brian -- Suh, Bernard -- Burhans, Richard -- Herrero, Javier -- Haussler, David -- Faria, Rui -- Fernando, Olga -- Darre, Fleur -- Farre, Domenec -- Gazave, Elodie -- Oliva, Meritxell -- Navarro, Arcadi -- Roberto, Roberta -- Capozzi, Oronzo -- Archidiacono, Nicoletta -- Della Valle, Giuliano -- Purgato, Stefania -- Rocchi, Mariano -- Konkel, Miriam K -- Walker, Jerilyn A -- Ullmer, Brygg -- Batzer, Mark A -- Smit, Arian F A -- Hubley, Robert -- Casola, Claudio -- Schrider, Daniel R -- Hahn, Matthew W -- Quesada, Victor -- Puente, Xose S -- Ordonez, Gonzalo R -- Lopez-Otin, Carlos -- Vinar, Tomas -- Brejova, Brona -- Ratan, Aakrosh -- Harris, Robert S -- Miller, Webb -- Kosiol, Carolin -- Lawson, Heather A -- Taliwal, Vikas -- Martins, Andre L -- Siepel, Adam -- Roychoudhury, Arindam -- Ma, Xin -- Degenhardt, Jeremiah -- Bustamante, Carlos D -- Gutenkunst, Ryan N -- Mailund, Thomas -- Dutheil, Julien Y -- Hobolth, Asger -- Schierup, Mikkel H -- Ryder, Oliver A -- Yoshinaga, Yuko -- de Jong, Pieter J -- Weinstock, George M -- Rogers, Jeffrey -- Mardis, Elaine R -- Gibbs, Richard A -- Wilson, Richard K -- G0501331/Medical Research Council/United Kingdom -- HG002238/HG/NHGRI NIH HHS/ -- HG002385/HG/NHGRI NIH HHS/ -- MC_U137761446/Medical Research Council/United Kingdom -- P01 AG022064/AG/NIA NIH HHS/ -- R01 GM059290/GM/NIGMS NIH HHS/ -- R01 GM59290/GM/NIGMS NIH HHS/ -- R01 HG002939/HG/NHGRI NIH HHS/ -- U54 HG003079/HG/NHGRI NIH HHS/ -- U54 HG003079-08/HG/NHGRI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Medical Research Council/United Kingdom -- England -- Nature. 2011 Jan 27;469(7331):529-33. doi: 10.1038/nature09687.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Genome Center at Washington University, Washington University School of Medicine, 4444 Forest Park Avenue, Saint Louis, Missouri 63108, USA. dlocke@wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21270892" target="_blank"〉PubMed〈/a〉