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Editorial

Cool as a cucumber p1259

doi:10.1038/ng1209-1259

The genome of the seventh plant to be sequenced, Cucumis sativus L., was assembled using the conventional long-read Sanger sequencing and higher-throughput short-read technology. This genome is the entry point for exploring the diversity and function of the Cucurbitaceae family of agriculturally important plants. Its compact genome, without evidence of recent duplication, will be useful in comparative analysis of plant genome evolution.


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News and Views

Evidence for a common pathway linking neurodegenerative diseases pp1261 - 1262

Joshua M Shulman & Philip L De Jager

doi:10.1038/ng1209-1261

In the largest Parkinson's disease genome-wide association studies to date, common variants in three familiar genes—SNCA, MAPT and LRRK2—and two new loci are found to increase disease susceptibility. The studies suggest genetic heterogeneity for Parkinson's disease risk in different human populations and lend support to the idea of a common pathway for Parkinson's and Alzheimer's diseases.

See also: Letter by Satake et al. | Letter by Simón-Sánchez et al.


Copy number variation and antigenic repertoire pp1263 - 1264

John A L Armour

doi:10.1038/ng1209-1263

The success of bone marrow transplantation depends on whether transplanted immune cells respond in graft versus host disease. A new study identifies a common gene deletion that is associated with immune response following transplantation.

See also: Letter by McCarroll et al.


Putting leprosy on the map pp1264 - 1266

Martin C J Maiden

doi:10.1038/ng1209-1264

Sequencing of the genome of a second strain of Mycobacterium leprae and the development of a genome-wide typing scheme have provided deeper understanding of the evolution and epidemiology of the leprosy bacillus. A new study confirms that leprosy has a single clone origin and has spread around the globe, following human migration and trade over the last several thousand years.

See also: Article by Monot et al.


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Research Highlights

Research highlights p1267

doi:10.1038/ng1209-1267


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Brief Communications

A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes pp1269 - 1271

Marwan Shinawi, Christian P Schaaf, Samarth S Bhatt, Zhilian Xia, Ankita Patel, Sau Wai Cheung, Brendan Lanpher, Sandra Nagl, Heinrich Stephan Herding, Claudia Nevinny-Stickel, LaDonna L Immken, Gayle Simpson Patel, Jennifer Ruth German, Arthur L Beaudet & Pawel Stankiewicz

doi:10.1038/ng.481

Arthur Beaudet and colleagues report a recurrent 680-kb deletion within chromosome 15q13.3 associated with a range of neurodevelopmental phenotypes, including developmental delay, mental retardation and seizures. The deletion lies within the previously reported 1.5-Mb 15q13.3 deletion and spans only two genes, CHRNA7 and OTUD7A.


Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans pp1272 - 1274

Marielle Alders, Benjamin M Hogan, Evisa Gjini, Faranak Salehi, Lihadh Al-Gazali, Eric A Hennekam, Eva E Holmberg, Marcel M A M Mannens, Margot F Mulder, G Johan A Offerhaus, Trine E Prescott, Eelco J Schroor, Joke B G M Verheij, Merlijn Witte, Petra J Zwijnenburg, Mikka Vikkula, Stefan Schulte-Merker & Raoul C Hennekam

doi:10.1038/ng.484

Raoul Hennekam and colleagues report the identification of mutations in CCBE1 that cause Hennekam syndrome in humans. Features of Hennekam syndrome include lymphedema, lymphangiectasias, mental retardation and unusual facial characteristics. CCBE1 encodes Collagen and Calcium-Binding EGF domain-1, a secreted protein that has been shown to be required for embryonic lymphangiogenesis in zebrafish.


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Articles

The genome of the cucumber, Cucumis sativus L. pp1275 - 1281

Sanwen Huang, Ruiqiang Li, Zhonghua Zhang, Li Li, Xingfang Gu, Wei Fan, William J Lucas, Xiaowu Wang, Bingyan Xie, Peixiang Ni, Yuanyuan Ren, Hongmei Zhu, Jun Li, Kui Lin, Weiwei Jin, Zhangjun Fei, Guangcun Li, Jack Staub, Andrzej Kilian, Edwin A G van der Vossen, Yang Wu, Jie Guo, Jun He, Zhiqi Jia, Yi Ren, Geng Tian, Yao Lu, Jue Ruan, Wubin Qian, Mingwei Wang, Quanfei Huang, Bo Li, Zhaoling Xuan, Jianjun Cao, Asan, Zhigang Wu, Juanbin Zhang, Qingle Cai, Yinqi Bai, Bowen Zhao, Yonghua Han, Ying Li, Xuefeng Li, Shenhao Wang, Qiuxiang Shi, Shiqiang Liu, Won Kyong Cho, Jae-Yean Kim, Yong Xu, Katarzyna Heller-Uszynska, Han Miao, Zhouchao Cheng, Shengping Zhang, Jian Wu, Yuhong Yang, Houxiang Kang, Man Li, Huiqing Liang, Xiaoli Ren, Zhongbin Shi, Ming Wen, Min Jian, Hailong Yang, Guojie Zhang, Zhentao Yang, Rui Chen, Shifang Liu, Jianwen Li, Lijia Ma, Hui Liu, Yan Zhou, Jing Zhao, Xiaodong Fang, Guoqing Li, Lin Fang, Yingrui Li, Dongyuan Liu, Hongkun Zheng, Yong Zhang, Nan Qin, Zhuo Li, Guohua Yang, Shuang Yang, Lars Bolund, Karsten Kristiansen, Hancheng Zheng, Shaochuan Li, Xiuqing Zhang, Huanming Yang, Jian Wang, Rifei Sun, Baoxi Zhang, Shuzhi Jiang, Jun Wang, Yongchen Du & Songgang Li

doi:10.1038/ng.475

Jun Wang and colleagues report the genome sequence of the cucumber. The cucumber genome is the seventh plant genome sequence to be reported and was assembled with a combination of traditional Sanger and next-generation sequencing methods.


Comparative genomic and phylogeographic analysis of Mycobacterium leprae pp1282 - 1289

Marc Monot, Nadine Honoré, Thierry Garnier, Nora Zidane, Diana Sherafi, Alberto Paniz-Mondolfi, Masanori Matsuoka, G Michael Taylor, Helen D Donoghue, Abi Bouwman, Simon Mays, Claire Watson, Diana Lockwood, Ali Khamispour, Yahya Dowlati, Shen Jianping, Thomas H Rea, Lucio Vera-Cabrera, Mariane M Stefani, Sayera Banu, Murdo Macdonald, Bishwa Raj Sapkota, John S Spencer, Jérôme Thomas, Keith Harshman, Pushpendra Singh, Philippe Busso, Alexandre Gattiker, Jacques Rougemont, Patrick J Brennan & Stewart T Cole

doi:10.1038/ng.477

Stewart Cole and colleagues report the genome sequence and comparative analyses of Brazilian, Indian, North American and Thai strains of Mycobacterium leprae, the etiologial agent of leprosy. They define 16 sub-types of M. leprae and examine their geographical distribution.

See also: News and Views by Maiden


HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C pp1290 - 1294

Rasmi Thomas, Richard Apps, Ying Qi, Xiaojiang Gao, Victoria Male, Colm O'hUigin, Geraldine O'Connor, Dongliang Ge, Jacques Fellay, Jeffrey N Martin, Joseph Margolick, James J Goedert, Susan Buchbinder, Gregory D Kirk, Maureen P Martin, Amalio Telenti, Steven G Deeks, Bruce D Walker, David Goldstein, Daniel W McVicar, Ashley Moffett & Mary Carrington

doi:10.1038/ng.486

Mary Carrington and colleagues follow up on an earlier association of a variant upstream of HLA-C to HIV viral load setpoint, showing that this variant is associated with high HLA-C cell surface expression and demonstrating a protective effect of the variant in viral load and disease progression.


Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis pp1295 - 1302

Benson C Lu, Cristina Cebrian, Xuan Chi, Satu Kuure, Richard Kuo, Carlton M Bates, Silvia Arber, John Hassell, Lesley MacNeil, Masato Hoshi, Sanjay Jain, Naoya Asai, Masahide Takahashi, Kai M Schmidt-Ott, Jonathan Barasch, Vivette D'Agati & Frank Costantini

doi:10.1038/ng.476

Frank Costantini and colleagues report the identification of the ETS transcription factors, Etv4 and Etv5, as key targets of Ret signaling during kidney branching morphogenesis. Loss of Etv4 and Etv5 function in mice leads to complete failure of kidney development.


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Letters

Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease pp1303 - 1307

Wataru Satake, Yuko Nakabayashi, Ikuko Mizuta, Yushi Hirota, Chiyomi Ito, Michiaki Kubo, Takahisa Kawaguchi, Tatsuhiko Tsunoda, Masahiko Watanabe, Atsushi Takeda, Hiroyuki Tomiyama, Kenji Nakashima, Kazuko Hasegawa, Fumiya Obata, Takeo Yoshikawa, Hideshi Kawakami, Saburo Sakoda, Mitsutoshi Yamamoto, Nobutaka Hattori, Miho Murata, Yusuke Nakamura & Tatsushi Toda

doi:10.1038/ng.485

Tatsushi Toda and colleagues report results of a genome-wide association study of Parkinson's disease in the Japanese population. They identify four loci harboring common variants associated with Parkinson's disease, including two newly discovered risk regions on 1q32 and 4p15.

See also: News and Views by Shulman & De Jager | Letter by Simón-Sánchez et al.


Genome-wide association study reveals genetic risk underlying Parkinson's disease pp1308 - 1312

Javier Simón-Sánchez, Claudia Schulte, Jose M Bras, Manu Sharma, J Raphael Gibbs, Daniela Berg, Coro Paisan-Ruiz, Peter Lichtner, Sonja W Scholz, Dena G Hernandez, Rejko Krüger, Monica Federoff, Christine Klein, Alison Goate, Joel Perlmutter, Michael Bonin, Michael A Nalls, Thomas Illig, Christian Gieger, Henry Houlden, Michael Steffens, Michael S Okun, Brad A Racette, Mark R Cookson, Kelly D Foote, Hubert H Fernandez, Bryan J Traynor, Stefan Schreiber, Sampath Arepalli, Ryan Zonozi, Katrina Gwinn, Marcel van der Brug, Grisel Lopez, Stephen J Chanock, Arthur Schatzkin, Yikyung Park, Albert Hollenbeck, Jianjun Gao, Xuemei Huang, Nick W Wood, Delia Lorenz, Günther Deuschl, Honglei Chen, Olaf Riess, John A Hardy, Andrew B Singleton & Thomas Gasser

doi:10.1038/ng.487

Andrew Singleton, Thomas Gasser and colleagues report results of a genome-wide association study of Parkinson's disease among individuals of European ancestry. They find genome-wide significant associations at two loci, SNCA and MAPT, and provide supporting evidence for a new risk locus on 1q32.

See also: News and Views by Shulman & De Jager | Letter by Satake et al.


Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk pp1313 - 1318

Soumya Raychaudhuri, Brian P Thomson, Elaine F Remmers, Stephen Eyre, Anne Hinks, Candace Guiducci, Joseph J Catanese, Gang Xie, Eli A Stahl, Robert Chen, Lars Alfredsson, Christopher I Amos, Kristin G Ardlie, BIRAC Consortium, Anne Barton, John Bowes, Noel P Burtt, Monica Chang, Jonathan Coblyn, Karen H Costenbader, Lindsey A Criswell, J Bart A Crusius, Jing Cui, Phillip L De Jager, Bo Ding, Paul Emery, Edward Flynn, Pille Harrison, Lynne J Hocking, Tom W J Huizinga, Daniel L Kastner, Xiayi Ke, Fina A S Kurreeman, Annette T Lee, Xiangdong Liu, Yonghong Li, Paul Martin, Ann W Morgan, Leonid Padyukov, David M Reid, Mark Seielstad, Michael F Seldin, Nancy A Shadick, Sophia Steer, Paul P Tak, Wendy Thomson, Annette H M van der Helm-van Mil, Irene E van der Horst-Bruinsma, Michael E Weinblatt, Anthony G Wilson, Gert Jan Wolbink, Paul Wordsworth, YEAR Consortium, David Altshuler, Elizabeth W Karlson, Rene E M Toes, Niek de Vries, Ann B Begovich, Katherine A Siminovitch, Jane Worthington, Lars Klareskog, Peter K Gregersen, Mark J Daly & Robert M Plenge

doi:10.1038/ng.479

Soumya Raychaudhuri and colleagues demonstrate the utility of GRAIL, a software program used to prioritize results from genome-wide association studies for further replication, applied here to rheumatoid arthritis. The authors seek replication of their predictions in additional independent cohorts and report three new genetic loci associated with RA susceptibility.


Specific interaction between genotype, smoking and autoimmunity to citrullinated alpha-enolase in the etiology of rheumatoid arthritis pp1319 - 1324

Hiba Mahdi, Benjamin A Fisher, Henrik Källberg, Darren Plant, Vivianne Malmström, Johan Rönnelid, Peter Charles, Bo Ding, Lars Alfredsson, Leonid Padyukov, Deborah P M Symmons, Patrick J Venables, Lars Klareskog & Karin Lundberg

doi:10.1038/ng.480

Karin Lundberg and colleagues explore gene-gene and gene-environment interactions in susceptibility to rheumatoid arthritis, reporting an association of HLA-DRB1, PTPN22 and smoking stratified by the autoantigen CEP-1.


A genome-wide association study identifies three new susceptibility loci for ulcerative colitis in the Japanese population pp1325 - 1329

Kouichi Asano, Tomonaga Matsushita, Junji Umeno, Naoya Hosono, Atsushi Takahashi, Takahisa Kawaguchi, Takayuki Matsumoto, Toshiyuki Matsui, Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa, Masayo Hosokawa, Yoshiaki Arimura, Yasuhisa Shinomura, Yutaka Kiyohara, Tatsuhiko Tsunoda, Naoyuki Kamatani, Mitsuo Iida, Yusuke Nakamura & Michiaki Kubo

doi:10.1038/ng.482

Michiaki Kubo and colleagues report results of a genome-wide association study of ulcerative colitis in the Japanese population. Their study identifies three new susceptibility loci for this common inflammatory bowel disease, including FCGR2A, which has previously been implicated in other autoimmune diseases.

See also: Letter by Barrett et al. | Letter by Imielinski et al.


Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region pp1330 - 1334

The UK IBD Genetics Consortium & the Wellcome Trust Case Control Consortium 2

doi:10.1038/ng.483

The UK IBD Genetics Consortium and the Wellcome Trust Case Control Consortium 2 report results of a genome-wide association study of ulcerative colitis. They identify three new loci associated with the disease, including the HNF4A region on 20q13.

See also: Letter by Asano et al. | Letter by Imielinski et al.


Common variants at five new loci associated with early-onset inflammatory bowel disease pp1335 - 1340

Marcin Imielinski, Robert N Baldassano, Anne Griffiths, Richard K Russell, Vito Annese, Marla Dubinsky, Subra Kugathasan, Jonathan P Bradfield, Thomas D Walters, Patrick Sleiman, Cecilia E Kim, Aleixo Muise, Kai Wang, Joseph T Glessner, Shehzad Saeed, Haitao Zhang, Edward C Frackelton, Cuiping Hou, James H Flory, George Otieno, Rosetta M Chiavacci, Robert Grundmeier, Massimo Castro, Anna Latiano, Bruno Dallapiccola, Joanne Stempak, Debra J Abrams, Kent Taylor, Dermot McGovern, Western Regional Research Alliance for Pediatric IBD, International IBD Genetics Consortium, Melvin B Heyman, George D Ferry, Barbara Kirschner, Jessica Lee, Jonah Essers, Richard Grand, Michael Stephens, Arie Levine, David Piccoli, Johan Van Limbergen, Salvatore Cucchiara, Dimitri S Monos, Stephen L Guthery, Lee Denson, David C Wilson, Struan F A Grant, Mark Daly, Mark S Silverberg, Jack Satsangi & Hakon Hakonarson

doi:10.1038/ng.489

Hakon Hakonarson and colleagues report the discovery of five new regions associated with susceptibility to early-onset inflammatory bowel disease. They also identify multiple loci previously implicated in the etiology of adult-onset Crohn's disease and/or ulcerative colitis as risk factors for early-onset forms of these diseases.

See also: Letter by Asano et al. | Letter by Barrett et al.


Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease pp1341 - 1344

Steven A McCarroll, James E Bradner, Hannu Turpeinen, Liisa Volin, Paul J Martin, Shannon D Chilewski, Joseph H Antin, Stephanie J Lee, Tapani Ruutu, Barry Storer, Edus H Warren, Bo Zhang, Lue Ping Zhao, David Ginsburg, Robert J Soiffer, Jukka Partanen, John A Hansen, Jerome Ritz, Aarno Palotie & David Altshuler

doi:10.1038/ng.490

Steven McCarroll and colleagues examine common gene deletions in individuals that have undergone bone marrow transplantation. They find that risk of acute graft-versus-host disease is greater when the donor and recipient are mismatched for a homozygous deletion of UGT2B17.

See also: News and Views by Armour


Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy pp1345 - 1349

Colin J D Ross, Hagit Katzov-Eckert, Marie-Pierre Dubé, Beth Brooks, S Rod Rassekh, Amina Barhdadi, Yassamin Feroz-Zada, Henk Visscher, Andrew M K Brown, Michael J Rieder, Paul C Rogers, Michael S Phillips, Bruce C Carleton, Michael R Hayden & the CPNDS Consortium

doi:10.1038/ng.478

Colin Ross and colleagues report the association of variants in TPMT and COMT to cisplatin-induced hearing loss in children.


Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts pp1350 - 1353

Akiko Doi, In-Hyun Park, Bo Wen, Peter Murakami, Martin J Aryee, Rafael Irizarry, Brian Herb, Christine Ladd-Acosta, Junsung Rho, Sabine Loewer, Justine Miller, Thorsten Schlaeger, George Q Daley & Andrew P Feinberg

doi:10.1038/ng.471

Andrew Feinberg and colleagues show that differential methylation of CpG island shores distinguish human induced pluripotent stem cells from the fibroblasts from which they were derived. These differentially methylated regions of the genome can also distinguish normal colon tissue from colorectal cancer.


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