Online Methods - p763

doi:10.1038/ng0709-763

Most of our readers access our articles online, in formats that deal well with increasingly complex research methods and the growing requirement for increased precision of citation. These considerations have now led us to publish Methods online.

Abstract - Online Methods | Full Text - Online Methods | PDF (73 KB) - Online Methods

High marks for GWAS - pp765 - 766

Stephen Chanock

doi:10.1038/ng0709-765

Abstract - High marks for GWAS | Full Text - High marks for GWAS | PDF (380 KB) - High marks for GWAS

See also: Letter by Rapley et al. | Letter by Kanetsky et al.

TET2 mutations in myelodysplasia and myeloid malignancies - pp766 - 767

Charles G Mullighan

doi:10.1038/ng0709-766

Abstract - TET2: mutations in myelodysplasia and myeloid malignancies | Full Text - TET2 mutations in myelodysplasia and myeloid malignancies | PDF (254 KB) - TET2 mutations in myelodysplasia and myeloid malignancies

See also: Letter by Langemeijer et al.

Tumors line up for a letdown - pp768 - 769

Joshua T Mendell

doi:10.1038/ng0709-768

Abstract - Tumors : lin: e up for a : let: down | Full Text - Tumors line up for a letdown | PDF (427 KB) - Tumors line up for a letdown

See also: Letter by Viswanathan et al.

Research highlights - p770

doi:10.1038/ng0709-770

Full Text - Research highlights | PDF (71 KB) - Research highlights

RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection - pp773 - 775

Marco Henneke, Simone Diekmann, Andreas Ohlenbusch, Jens Kaiser, Volkher Engelbrecht, Alfried Kohlschütter, Ralph Krätzner, Marcos Madruga-Garrido, Michèle Mayer, Lennart Opitz, Diana Rodriguez, Franz Rüschendorf, Johannes Schumacher, Holger Thiele, Sven Thoms, Robert Steinfeld, Peter Nürnberg & Jutta Gärtner

doi:10.1038/ng.398

Jutta Gartner and colleagues identify five pathologic mutant alleles in the RNASET2 gene that compromise its enzymatic activity and that are responsible for the CMV infection–like neurological disorder cystic leukoencephalopathy without megalencephaly (CLM).

Abstract - RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection | Full Text - RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection | PDF (243 KB) - RNASET2-deficient cystic leukoencephalopathy resembles congenital cytomegalovirus brain infection | Supplementary information

Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci - pp776 - 782

Philip L De Jager, Xiaoming Jia, Joanne Wang, Paul I W de Bakker, Linda Ottoboni, Neelum T Aggarwal, Laura Piccio, Soumya Raychaudhuri, Dong Tran, Cristin Aubin, Rebeccah Briskin, Susan Romano, International MS Genetics Consortium, Sergio E Baranzini, Jacob L McCauley, Margaret A Pericak-Vance, Jonathan L Haines, Rachel A Gibson, Yvonne Naeglin, Bernard Uitdehaag, Paul M Matthews, Ludwig Kappos, Chris Polman, Wendy L McArdle, David P Strachan, Denis Evans, Anne H Cross, Mark J Daly, Alastair Compston, Stephen J Sawcer, Howard L Weiner, Stephen L Hauser, David A Hafler & Jorge R Oksenberg

doi:10.1038/ng.401

Philip De Jager and colleagues report results of a large genome-wide association and replication study for multiple sclerosis. The work uncovers three new susceptibility loci for MS, including common and rare variants at TNFRSF1A and common variants at IRF8 and CD6.

Abstract - Meta-analysis of genome scans and replication identify : CD6: , : IRF8: and : TNFRSF1A: as new multiple sclerosis susceptibility loci | Full Text - Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci | PDF (385 KB) - Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci | Supplementary information

Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia - pp783 - 792

Yaoyu Chen, Yiguo Hu, Haojian Zhang, Cong Peng & Shaoguang Li

doi:10.1038/ng.389

Shaoguang Li and colleagues identify Alox5 as a key gene that regulates the function of leukemia stem cells but not normal hematopoietic stem cells in mice, highlighting how cancer and normal stem cells distinctly self-renew and differentiate.

Abstract - Loss of the : Alox5: gene impairs leukemia stem cells and prevents chronic myeloid leukemia | Full Text - Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia | PDF (919 KB) - Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia | Supplementary information

Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis - pp793 - 799

Courtney M Karner, Rani Chirumamilla, Shigehisa Aoki, Peter Igarashi, John B Wallingford & Thomas J Carroll

doi:10.1038/ng.400

Thomas Carroll and colleagues show that attenuation of Wnt9b signaling during kidney morphogenesis affects planar cell polarity and causes an increase in tubule diameter. Their analyses suggest that tubule diameter is established by convergent extension movements and subsequently maintained by polarized cell divisions.

Abstract - Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis | Full Text - Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis | PDF (672 KB) - Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis | Supplementary information

The establishment of gene silencing at single-cell resolution - pp800 - 806

Erin A Osborne, Sandrine Dudoit & Jasper Rine

doi:10.1038/ng.402

Jasper Rine and colleagues examine the silencing of the HML locus in synchronous S. cerevisiae cells at single-cell resolution. They demonstrate that the establishment of silencing under native conditions occurs rapidly, within two cell cycles.

Abstract - The establishment of gene silencing at single-cell resolution | Full Text - The establishment of gene silencing at single-cell resolution | PDF (349 KB) - The establishment of gene silencing at single-cell resolution | Supplementary information

A genome-wide association study of testicular germ cell tumor - pp807 - 810

Elizabeth A Rapley, Clare Turnbull, Ali Amin Al Olama, Emmanouil T Dermitzakis, Rachel Linger, Robert A Huddart, Anthony Renwick, Deborah Hughes, Sarah Hines, Sheila Seal, Jonathan Morrison, Jeremie Nsengimana, Panagiotis Deloukas, The UK Testicular Cancer Collaboration, Nazneen Rahman, D Timothy Bishop, Douglas F Easton & Michael R Stratton

doi:10.1038/ng.394

Michael Stratton and colleagues report a genome-wide association study for testicular germ cell tumor (TGCT) in a UK population, identifying three associated loci.

First Paragraph - A genome-wide association study of testicular germ cell tumor | Full Text - A genome-wide association study of testicular germ cell tumor | PDF (171 KB) - A genome-wide association study of testicular germ cell tumor | Supplementary information

See also: News and Views by Chanock | Letter by Kanetsky et al.

Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer - pp811 - 815

Peter A Kanetsky, Nandita Mitra, Saran Vardhanabhuti, Mingyao Li, David J Vaughn, Richard Letrero, Stephanie L Ciosek, David R Doody, Lauren M Smith, JoEllen Weaver, Anthony Albano, Chu Chen, Jacqueline R Starr, Daniel J Rader, Andrew K Godwin, Muredach P Reilly, Hakon Hakonarson, Stephen M Schwartz & Katherine L Nathanson

doi:10.1038/ng.393

Katherine Nathanson and colleagues report a genome-wide association study identifying two loci associated with susceptibility to testicular germ cell tumor.

First Paragraph - Common variation in : KITLG: and at 5q31.3 predisposes to testicular germ cell cancer | Full Text - Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer | PDF (267 KB) - Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer | Supplementary information

See also: News and Views by Chanock | Letter by Rapley et al.

HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin - pp816 - 819

Ann K Daly, Peter T Donaldson, Pallav Bhatnagar, Yufeng Shen, Itsik Pe'er, Aris Floratos, Mark J Daly, David B Goldstein, Sally John, Matthew R Nelson, Julia Graham, B Kevin Park, John F Dillon, William Bernal, Heather J Cordell, Munir Pirmohamed, Guruprasad P Aithal, Christopher P Day, for the DILIGEN study & International SAE Consortium

doi:10.1038/ng.379

Ann Daly and colleagues report results of a genome-wide association study to identify common variants associated with drug-induced liver injury due to flucloxacillin. They show that carriers of the HLA-B*5701 allele in the MHC region are at 80-fold increased risk of developing this severe adverse drug reaction.

First Paragraph - HLA-B[ast]5701: genotype is a major determinant of drug-induced liver injury due to flucloxacillin | Full Text - HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin | PDF (251 KB) - HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin | Supplementary information

REL, encoding a member of the NF-B family of transcription factors, is a newly defined risk locus for rheumatoid arthritis - pp820 - 823

Peter K Gregersen, Chistopher I Amos, Annette T Lee, Yue Lu, Elaine F Remmers, Daniel L Kastner, Michael F Seldin, Lindsey A Criswell, Robert M Plenge, V Michael Holers, Ted R Mikuls, Tuulikki Sokka, Larry W Moreland, S Louis Bridges Jr, Gang Xie, Ann B Begovich & Katherine A Siminovitch

doi:10.1038/ng.395

Peter Gregersen and colleagues report that common variants at the REL locus are associated with risk of rheumatoid arthritis. REL encodes a member of the NF-B family of transcription factors, which play key roles in coordinating immune and inflammatory responses.

Abstract - REL: , encoding a member of the NF-[kappa]B family of transcription factors, is a newly defined risk locus for rheumatoid arthritis | Full Text - REL, encoding a member of the NF-B family of transcription factors, is a newly defined risk locus for rheumatoid arthritis | PDF (349 KB) - REL, encoding a member of the NF-B family of transcription factors, is a newly defined risk locus for rheumatoid arthritis | Supplementary information

Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20 - pp824 - 828

The Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene)

doi:10.1038/ng.396

Justin Rubio and colleagues report results of a genome-wide association study of multiple sclerosis using cases from Australia and New Zealand. Their findings confirm several published risk loci for MS and identify two new risk loci on chromosomes 12 and 20.

First Paragraph - Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20 | Full Text - Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20 | PDF (501 KB) - Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20 | Supplementary information

Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response - pp829 - 832

Gillian I Rice, Jacquelyn Bond, Aruna Asipu, Rebecca L Brunette, Iain W Manfield, Ian M Carr, Jonathan C Fuller, Richard M Jackson, Teresa Lamb, Tracy A Briggs, Manir Ali, Hannah Gornall, Lydia R Couthard, Alec Aeby, Simon P Attard-Montalto, Enrico Bertini, Christine Bodemer, Knut Brockmann, Louise A Brueton, Peter C Corry, Isabelle Desguerre, Elisa Fazzi, Angels Garcia Cazorla, Blanca Gener, Ben C J Hamel, Arvid Heiberg, Matthew Hunter, Marjo S van der Knaap, Ram Kumar, Lieven Lagae, Pierre G Landrieu, Charles M Lourenco, Daphna Marom, Michael F McDermott, William van der Merwe, Simona Orcesi, Julie S Prendiville, Magnhild Rasmussen, Stavit A Shalev, Doriette M Soler, Marwan Shinawi, Ronen Spiegel, Tiong Y Tan, Adeline Vanderver, Emma L Wakeling, Evangeline Wassmer, Elizabeth Whittaker, Pierre Lebon, Daniel B Stetson, David T Bonthron & Yanick J Crow

doi:10.1038/ng.373

Aicardi-Goutieres syndrome is a genetically determined encephalopathy that is associated with an increased production of interferon alpha, which in turn is central to the pathogenesis of systemic lupus erythematosus. Yanick Crow and colleagues now identify homozygous mutations in an interferon-inducible nuclear gene encoding SAMHD1 in AGS-affected individuals across several pedigrees and characterize its function in modulating an innate immune response.

First Paragraph - Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response | Full Text - Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response | PDF (313 KB) - Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response | Supplementary information

Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome - pp833 - 837

Woranontee Weraarpachai, Hana Antonicka, Florin Sasarman, Jürgen Seeger, Bertold Schrank, Jill E Kolesar, Hanns Lochmüller, Mario Chevrette, Brett A Kaufman, Rita Horvath & Eric A Shoubridge

doi:10.1038/ng.390

Eric Shoubridge and colleagues report the identification of a mutation in the CCDC44 gene that is causal in a Leigh syndrome pedigree. The CCDC44 gene product, TACO1, is involved in mitochondrial translation and is the first specific mitochondrial translational activator identified in mammals.

First Paragraph - Mutation in : TACO1: , encoding a translational activator of COX I, results in cytochrome : c: oxidase deficiency and late-onset Leigh syndrome | Full Text - Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome | PDF (403 KB) - Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome | Supplementary information

Acquired mutations in TET2 are common in myelodysplastic syndromes - pp838 - 842

Saskia M C Langemeijer, Roland P Kuiper, Marieke Berends, Ruth Knops, Mariam G Aslanyan, Marion Massop, Ellen Stevens-Linders, Patricia van Hoogen, Ad Geurts van Kessel, Reinier A P Raymakers, Eveline J Kamping, Gregor E Verhoef, Estelle Verburgh, Anne Hagemeijer, Peter Vandenberghe, Theo de Witte, Bert A van der Reijden & Joop H Jansen

doi:10.1038/ng.391

Joop Jansen and colleagues show that myelodysplastic syndromes frequently harbor somatic mutations in TET2. Analysis of lineage markers suggests that TET2 mutations are early events contributing to malignant transformation.

First Paragraph - Acquired mutations in : TET2: are common in myelodysplastic syndromes | Full Text - Acquired mutations in TET2 are common in myelodysplastic syndromes | PDF (572 KB) - Acquired mutations in TET2 are common in myelodysplastic syndromes | Supplementary information

See also: News and Views by Mullighan

Lin28 promotes transformation and is associated with advanced human malignancies - pp843 - 848

Srinivas R Viswanathan, John T Powers, William Einhorn, Yujin Hoshida, Tony L Ng, Sara Toffanin, Maureen O'Sullivan, Jun Lu, Letha A Phillips, Victoria L Lockhart, Samar P Shah, Pradeep S Tanwar, Craig H Mermel, Rameen Beroukhim, Mohammad Azam, Jose Teixeira, Matthew Meyerson, Timothy P Hughes, Josep M Llovet, Jerald Radich, Charles G Mullighan, Todd R Golub, Poul H Sorensen & George Q Daley

doi:10.1038/ng.392

George Daley and colleagues show that Lin28 and Lin28B promote cellular transformation by repressing let-7 family members, leading to derepression of let-7 targets. They also find that LIN28 and LIN28B are overexpressed in 15% of primary human tumors and cancer cell lines and that their expression is associated with aggressive disease and poor prognosis across multiple tumor types.

First Paragraph - Lin28 promotes transformation and is associated with advanced human malignancies | Full Text - Lin28 promotes transformation and is associated with advanced human malignancies | PDF (394 KB) - Lin28 promotes transformation and is associated with advanced human malignancies | Supplementary information

See also: News and Views by Mendell

The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans - pp849 - 853

Feng Zhang, Mehrdad Khajavi, Anne M Connolly, Charles F Towne, Sat Dev Batish & James R Lupski

doi:10.1038/ng.399

James Lupski and colleagues provide evidence that a replication-based mechanism termed FoSTeS/MMBIR can mediate rearrangements in humans ranging in size from a few hundred base pairs to several megabases. They propose that FoSTeS/MMBIR could be an important mechanism for generating structural variation.

First Paragraph - The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans | Full Text - The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans | PDF (590 KB) - The DNA replication FoSTeS/MMBIR mechanism can generate genomic, genic and exonic complex rearrangements in humans | Supplementary information

Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons - pp854 - 858

David A Lyons, Stephen G Naylor, Anja Scholze & William S Talbot

doi:10.1038/ng.376

William Talbot and colleagues show that a kinesin motor protein, Kif1b, is required for the specific localization of mRNAs that encode myelin proteins in central nervous system glia and mediates the development of myelinated axons. Kif1b has previously been linked to the susceptibility of multiple sclerosis, and damage to myelinated axons is central to the symptoms associated with multiple sclerosis. This suggests mechanisms by which defects in Kif1b may contribute to the disease.

First Paragraph - Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons | Full Text - Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons | PDF (1,195 KB) - Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons | Supplementary information

Corrigendum: Tiny RNAs associated with transcription start sites in animals - p859

Ryan J Taft, Evgeny A Glazov, Nicole Cloonan, Cas Simons, Stuart Stephen, Geoffrey J Faulkner, Timo Lassmann, Alistair R R Forrest, Sean M Grimmond, Kate Schroder, Katharine Irvine, Takahiro Arakawa, Mari Nakamura, Atsutaka Kubosaki, Kengo Hayashida, Chika Kawazu, Mitsuyoshi Murata, Hiromi Nishiyori, Shiro Fukuda, Jun Kawai, Carsten O Daub, David A Hume, Harukazu Suzuki, Valerio Orlando, Piero Carninci, Yoshihide Hayashizaki & John S Mattick

doi:10.1038/ng0709-859a

Full Text - Corrigendum: Tiny RNAs associated with transcription start sites in animals | PDF (54 KB) - Corrigendum: Tiny RNAs associated with transcription start sites in animals

Erratum: Narcolepsy is strongly associated with the T-cell receptor alpha locus - p859

Joachim Hallmayer, Juliette Faraco, Ling Lin, Stephanie Hesselson, Juliane Winkelmann, Minae Kawashima, Geert Mayer, Giuseppe Plazzi, Sona Nevsimalova, Patrice Bourgin, Sheng Seung-Chul Hong, Yutaka Honda, Makoto Honda, Birgit Högl, William T Longstreth Jr, Jacques Montplaisir, David Kemlink, Mali Einen, Justin Chen, Stacy L Musone, Matthew Akana, Taku Miyagawa, Jubao Duan, Alex Desautels, Christine Erhardt, Per Egil Hesla, Francesca Poli, Birgit Frauscher, Jong-Hyun Jeong, Sung-Pil Lee, Thanh G N Ton, Mark Kvale, Libor Kolesar, Marie Dobrovolná, Gerald T Nepom, Dan Salomon, H-Erich Wichmann, Guy A Rouleau, Christian Gieger, Douglas F Levinson, Pablo V Gejman, Thomas Meitinger, Terry Young, Paul Peppard, Katsushi Tokunaga, Pui-Yan Kwok, Neil Risch & Emmanuel Mignot

doi:10.1038/ng0709-859b

Full Text - Erratum: Narcolepsy is strongly associated with the T-cell receptor alpha locus | PDF (55 KB) - Erratum: Narcolepsy is strongly associated with the T-cell receptor alpha locus