Teamwork - p1

doi:10.1038/ng0109-1

An increasing number of research papers are the products of research consortia. How is the journal coping with the effects of team knowledge production on publication? What can you do to expedite the publication of your work?

Abstract - | Full Text - Teamwork | PDF (141 KB) - Teamwork

Without apology - p3

Robin Bennett reviews Heredity and Hope: The Case for Genetic Screening by Ruth Schwartz Cowan

doi:10.1038/ng0109-3

Full Text - Without apology | PDF (141 KB) - Without apology

Cohort studies and the genetics of complex disease - pp5 - 6

Teri A Manolio

doi:10.1038/ng0109-5

Three new studies identify nearly 20 new loci for serum lipid levels using predominantly a prospective cohort study design which also permits extensive and unbiased characterization of environmental exposures. Given the known, strong environmental influences on these traits, investigation of gene-environment interactions should be emphasized in attempts to understand the complete epidemiologic and genetic architecture of these complex traits.

Abstract - | Full Text - Cohort studies and the genetics of complex disease | PDF (316 KB) - Cohort studies and the genetics of complex disease

See also: Article by Sabatti et al. | Article by Aulchenko et al. | Article by Kathiresan et al.

Searching for targets of viral microRNAs - pp7 - 8

Denise Whitby

doi:10.1038/ng0109-7

The identification of targets of virally encoded microRNAs is essential to understanding their role in the viral life cycle. A new study reports the successful use of a microarray-based approach to identify a key target of a microRNA encoded by Kaposi's sarcoma–associated herpesvirus, with implications for microRNA target identification in other contexts as well.

Abstract - | Full Text - Searching for targets of viral microRNAs | PDF (133 KB) - Searching for targets of viral microRNAs

See also: Letter by Ziegelbauer et al.

Evaluating signatures of sex-specific processes in the human genome - pp8 - 10

Carlos D Bustamante & Sohini Ramachandran

doi:10.1038/ng0109-8

Comparing levels of genetic variation between the X chromosome and autosomes can reveal the different demographic histories of males and females of a species. Taking this approach, two new studies report that the effective population sizes of men and women differ, but they disagree as to which sex outnumbered the other.

Abstract - | Full Text - Evaluating signatures of sex-specific processes in the human genome | PDF (220 KB) - Evaluating signatures of sex-specific processes in the human genome

See also: Letter by Keinan et al.

Protein demethylation required for DNA methylation - pp10 - 11

Hans-Rudolf Hotz & Antoine H F M Peters

doi:10.1038/ng0109-10

DNA methylation is an epigenetic mark directing stable, heritable gene silencing through development. A new study uncovers the importance of demethylation of the DNA methyltransferase-1 for maintenance of DNA methylation.

Abstract - | Full Text - Protein demethylation required for DNA methylation | PDF (631 KB) - Protein demethylation required for DNA methylation

See also: Letter by Wang et al.

Research Highlights - p13

doi:10.1038/ng0109-13

Full Text - Research Highlights | PDF (132 KB) - Research Highlights

New sequence variants associated with bone mineral density - pp15 - 17

Unnur Styrkarsdottir, Bjarni V Halldorsson, Solveig Gretarsdottir, Daniel F Gudbjartsson, G Bragi Walters, Thorvaldur Ingvarsson, Thorbjorg Jonsdottir, Jona Saemundsdottir, Steinunn Snorradóttir, Jacqueline R Center, Tuan V Nguyen, Peter Alexandersen, Jeffrey R Gulcher, John A Eisman, Claus Christiansen, Gunnar Sigurdsson, Augustine Kong, Unnur Thorsteinsdottir & Kari Stefansson

doi:10.1038/ng.284

Unnur Styrkarsdottir and Kari Stefansson and colleagues report the results of an expanded genome-wide association study for bone mineral density at the hip or the spine. New SNP associations were identified downstream of the SOST gene on 17q21, and in intron 1 of the MARK3 gene on 14q32.

Abstract - | Full Text - New sequence variants associated with bone mineral density | PDF (243 KB) - New sequence variants associated with bone mineral density | Supplementary information

Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity - pp18 - 24

Gudmar Thorleifsson, G Bragi Walters, Daniel F Gudbjartsson, Valgerdur Steinthorsdottir, Patrick Sulem, Anna Helgadottir, Unnur Styrkarsdottir, Solveig Gretarsdottir, Steinunn Thorlacius, Ingileif Jonsdottir, Thorbjorg Jonsdottir, Elinborg J Olafsdottir, Gudridur H Olafsdottir, Thorvaldur Jonsson, Frosti Jonsson, Knut Borch-Johnsen, Torben Hansen, Gitte Andersen, Torben Jorgensen, Torsten Lauritzen, Katja K Aben, André LM Verbeek, Nel Roeleveld, Ellen Kampman, Lisa R Yanek, Lewis C Becker, Laufey Tryggvadottir, Thorunn Rafnar, Diane M Becker, Jeffrey Gulcher, Lambertus A Kiemeney, Oluf Pedersen, Augustine Kong, Unnur Thorsteinsdottir & Kari Stefansson

doi:10.1038/ng.274

Gudmar Thorleifsson and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Joel Hirschhorn and colleagues.

Abstract - | Full Text - Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity | PDF (307 KB) - Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity | Supplementary information

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation - pp25 - 34

Cristen J Willer, Elizabeth K Speliotes, Ruth J F Loos, Shengxu Li, Cecilia M Lindgren, Iris M Heid, Sonja I Berndt, Amanda L Elliott, Anne U Jackson, Claudia Lamina, Guillaume Lettre, Noha Lim, Helen N Lyon, Steven A McCarroll, Konstantinos Papadakis, Lu Qi, Joshua C Randall, Rosa Maria Roccasecca, Serena Sanna, Paul Scheet, Michael N Weedon, Eleanor Wheeler, Jing Hua Zhao, Leonie C Jacobs, Inga Prokopenko, Nicole Soranzo, Toshiko Tanaka, Nicholas J Timpson, Peter Almgren, Amanda Bennett, Richard N Bergman, Sheila A Bingham, Lori L Bonnycastle, Morris Brown, Noël P Burtt, Peter Chines, Lachlan Coin, Francis S Collins, John M Connell, Cyrus Cooper, George Davey Smith, Elaine M Dennison, Parimal Deodhar, Paul Elliott, Michael R Erdos, Karol Estrada, David M Evans, Lauren Gianniny, Christian Gieger, Christopher J Gillson, Candace Guiducci, Rachel Hackett, David Hadley, Alistair S Hall, Aki S Havulinna, Johannes Hebebrand, Albert Hofman, Bo Isomaa, Kevin B Jacobs, Toby Johnson, Pekka Jousilahti, Zorica Jovanovic, Kay-Tee Khaw, Peter Kraft, Mikko Kuokkanen, Johanna Kuusisto, Jaana Laitinen, Edward G Lakatta, Jian'an Luan, Robert N Luben, Massimo Mangino, Wendy L McArdle, Thomas Meitinger, Antonella Mulas, Patricia B Munroe, Narisu Narisu, Andrew R Ness, Kate Northstone, Stephen O'Rahilly, Carolin Purmann, Matthew G Rees, Martin Ridderstråle, Susan M Ring, Fernando Rivadeneira, Aimo Ruokonen, Manjinder S Sandhu, Jouko Saramies, Laura J Scott, Angelo Scuteri, Kaisa Silander, Matthew A Sims, Kijoung Song, Jonathan Stephens, Suzanne Stevens, Heather M Stringham, Y C Loraine Tung, Timo T Valle, Cornelia M Van Duijn, Karani S Vimaleswaran, Peter Vollenweider, Gerard Waeber, Chris Wallace, Richard M Watanabe, Dawn M Waterworth, Nicholas Watkins, Jacqueline C M Witteman, Eleftheria Zeggini, Guangju Zhai, M Carola Zillikens, David Altshuler, Mark J Caulfield, Stephen J Chanock, I Sadaf Farooqi, Luigi Ferrucci, Jack M Guralnik, Andrew T Hattersley, Frank B Hu, Marjo-Riitta Jarvelin, Markku Laakso, Vincent Mooser, Ken K Ong, Willem H Ouwehand, Veikko Salomaa, Nilesh J Samani, Timothy D Spector, Tiinamaija Tuomi, Jaakko Tuomilehto, Manuela Uda, André G Uitterlinden, Nicholas J Wareham, Panagiotis Deloukas, Timothy M Frayling, Leif C Groop, Richard B Hayes, David J Hunter, Karen L Mohlke, Leena Peltonen, David Schlessinger, David P Strachan, H-Erich Wichmann, Mark I McCarthy, Michael Boehnke, Inês Barroso, Gonçalo R Abecasis & Joel N Hirschhorn for the GIANT Consortium

doi:10.1038/ng.287

Joel Hirschhorn and colleagues report results of a large-scale genome-wide association and replication study for obesity-related traits. The newly discovered loci are enriched for genes expressed in the central nervous system, and may thus contribute to weight gain by modulating food intake. Similar results are reported in a related study by Gudmar Thorleifsson and colleagues.

Abstract - | Full Text - Six new loci associated with body mass index highlight a neuronal influence on body weight regulation | PDF (753 KB) - Six new loci associated with body mass index highlight a neuronal influence on body weight regulation | Supplementary information

Genome-wide association analysis of metabolic traits in a birth cohort from a founder population - pp35 - 46

Chiara Sabatti, Susan K Service, Anna-Liisa Hartikainen, Anneli Pouta, Samuli Ripatti, Jae Brodsky, Chris G Jones, Noah A Zaitlen, Teppo Varilo, Marika Kaakinen, Ulla Sovio, Aimo Ruokonen, Jaana Laitinen, Eveliina Jakkula, Lachlan Coin, Clive Hoggart, Andrew Collins, Hannu Turunen, Stacey Gabriel, Paul Elliot, Mark I McCarthy, Mark J Daly, Marjo-Riitta Järvelin, Nelson B Freimer & Leena Peltonen

doi:10.1038/ng.271

Nelson Freimer and colleagues report the first genome-wide association study of a longitudinal birth cohort (the Northern Finland Birth Cohort 1966). The results include new associations for nine quantitative metabolic traits.

Abstract - | Full Text - Genome-wide association analysis of metabolic traits in a birth cohort from a founder population | PDF (13,340 KB) - Genome-wide association analysis of metabolic traits in a birth cohort from a founder population | Supplementary information

See also: News and Views by Manolio | Article by Aulchenko et al. | Article by Kathiresan et al.

Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts - pp47 - 55

Yurii S Aulchenko, Samuli Ripatti, Ida Lindqvist, Dorret Boomsma, Iris M Heid, Peter P Pramstaller, Brenda W J H Penninx, A Cecile J W Janssens, James F Wilson, Tim Spector, Nicholas G Martin, Nancy L Pedersen, Kirsten Ohm Kyvik, Jaakko Kaprio, Albert Hofman, Nelson B Freimer, Marjo-Riitta Jarvelin, Ulf Gyllensten, Harry Campbell, Igor Rudan, Åsa Johansson, Fabio Marroni, Caroline Hayward, Veronique Vitart, Inger Jonasson, Cristian Pattaro, Alan Wright, Nick Hastie, Irene Pichler, Andrew A Hicks, Mario Falchi, Gonneke Willemsen, Jouke-Jan Hottenga, Eco J C de Geus, Grant W Montgomery, John Whitfield, Patrik Magnusson, Juha Saharinen, Markus Perola, Kaisa Silander, Aaron Isaacs, Eric J G Sijbrands, Andre G Uitterlinden, Jacqueline C M Witteman, Ben A Oostra, Paul Elliott, Aimo Ruokonen, Chiara Sabatti, Christian Gieger, Thomas Meitinger, Florian Kronenberg, Angela Döring, H-Erich Wichmann, Johannes H Smit, Mark I McCarthy, Cornelia M van Duijn & Leena Peltonen for the ENGAGE Consortium

doi:10.1038/ng.269

Leena Peltonen and colleagues report a genome-wide association study of cholesterol and triglyceride levels in 16 population-based cohorts across Europe. Six new loci were identified, and overall a genetic risk score improves the screening of high risk groups for dyslipidemia.

Abstract - | Full Text - Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts | PDF (487 KB) - Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts | Supplementary information

See also: News and Views by Manolio | Article by Sabatti et al. | Article by Kathiresan et al.

Common variants at 30 loci contribute to polygenic dyslipidemia - pp56 - 65

Sekar Kathiresan, Cristen J Willer, Gina M Peloso, Serkalem Demissie, Kiran Musunuru, Eric E Schadt, Lee Kaplan, Derrick Bennett, Yun Li, Toshiko Tanaka, Benjamin F Voight, Lori L Bonnycastle, Anne U Jackson, Gabriel Crawford, Aarti Surti, Candace Guiducci, Noel P Burtt, Sarah Parish, Robert Clarke, Diana Zelenika, Kari A Kubalanza, Mario A Morken, Laura J Scott, Heather M Stringham, Pilar Galan, Amy J Swift, Johanna Kuusisto, Richard N Bergman, Jouko Sundvall, Markku Laakso, Luigi Ferrucci, Paul Scheet, Serena Sanna, Manuela Uda, Qiong Yang, Kathryn L Lunetta, Josée Dupuis, Paul I W de Bakker, Christopher J O'Donnell, John C Chambers, Jaspal S Kooner, Serge Hercberg, Pierre Meneton, Edward G Lakatta, Angelo Scuteri, David Schlessinger, Jaakko Tuomilehto, Francis S Collins, Leif Groop, David Altshuler, Rory Collins, G Mark Lathrop, Olle Melander, Veikko Salomaa, Leena Peltonen, Marju Orho-Melander, Jose M Ordovas, Michael Boehnke, Gonçalo R Abecasis, Karen L Mohlke & L Adrienne Cupples

doi:10.1038/ng.291

Sekar Kathiresan et al. report genome-wide association studies for polygenic dyslipidemia. From a meta-analysis of seven genome-wide association studies and follow-up in five replication studies, they identify 11 new genetic associations for LDL cholesterol, HDL cholesterol and triglycerides.

Abstract - | Full Text - Common variants at 30 loci contribute to polygenic dyslipidemia | PDF (787 KB) - Common variants at 30 loci contribute to polygenic dyslipidemia | Supplementary information

See also: News and Views by Manolio | Article by Sabatti et al. | Article by Aulchenko et al.

Accelerated genetic drift on chromosome X during the human dispersal out of Africa - pp66 - 70

Alon Keinan, James C Mullikin, Nick Patterson & David Reich

doi:10.1038/ng.303

David Reich and colleagues report evidence for accelerated genetic drift on the X chromosome, on the basis of population genetic analyses comparing patterns of genetic variation on the X chromosome and the autosomes in West African, North European and East Asian datasets.

First Paragraph - | Full Text - Accelerated genetic drift on chromosome X during the human dispersal out of Africa | PDF (293 KB) - Accelerated genetic drift on chromosome X during the human dispersal out of Africa | Supplementary information

See also: News and Views by Bustamante & Ramachandran

Common variants in the NLRP3 region contribute to Crohn's disease susceptibility - pp71 - 76

Alexandra-Chloé Villani, Mathieu Lemire, Geneviève Fortin, Edouard Louis, Mark S Silverberg, Catherine Collette, Nobuyasu Baba, Cécile Libioulle, Jacques Belaiche, Alain Bitton, Daniel Gaudet, Albert Cohen, Diane Langelier, Paul R Fortin, Joan E Wither, Marika Sarfati, Paul Rutgeerts, John D Rioux, Severine Vermeire, Thomas J Hudson & Denis Franchimont

doi:10.1038/ng.285

Alexandra-Chloé Villani and colleagues have identified SNPs located on chromosome 1q44 downstream of the NLRP3 gene that are associated with increased risk of Crohn's disease.

First Paragraph - | Full Text - Common variants in the NLRP3 region contribute to Crohn's disease susceptibility | PDF (676 KB) - Common variants in the NLRP3 region contribute to Crohn's disease susceptibility | Supplementary information

Variants in MTNR1B influence fasting glucose levels - pp77 - 81

Inga Prokopenko, Claudia Langenberg, Jose C Florez, Richa Saxena, Nicole Soranzo, Gudmar Thorleifsson, Ruth J F Loos, Alisa K Manning, Anne U Jackson, Yurii Aulchenko, Simon C Potter, Michael R Erdos, Serena Sanna, Jouke-Jan Hottenga, Eleanor Wheeler, Marika Kaakinen, Valeriya Lyssenko, Wei-Min Chen, Kourosh Ahmadi, Jacques S Beckmann, Richard N Bergman, Murielle Bochud, Lori L Bonnycastle, Thomas A Buchanan, Antonio Cao, Alessandra Cervino, Lachlan Coin, Francis S Collins, Laura Crisponi, Eco J C de Geus, Abbas Dehghan, Panos Deloukas, Alex S F Doney, Paul Elliott, Nelson Freimer, Vesela Gateva, Christian Herder, Albert Hofman, Thomas E Hughes, Sarah Hunt, Thomas Illig, Michael Inouye, Bo Isomaa, Toby Johnson, Augustine Kong, Maria Krestyaninova, Johanna Kuusisto, Markku Laakso, Noha Lim, Ulf Lindblad, Cecilia M Lindgren, Owen T McCann, Karen L Mohlke, Andrew D Morris, Silvia Naitza, Marco Orrù, Colin N A Palmer, Anneli Pouta, Joshua Randall, Wolfgang Rathmann, Jouko Saramies, Paul Scheet, Laura J Scott, Angelo Scuteri, Stephen Sharp, Eric Sijbrands, Jan H Smit, Kijoung Song, Valgerdur Steinthorsdottir, Heather M Stringham, Tiinamaija Tuomi, Jaakko Tuomilehto, André G Uitterlinden, Benjamin F Voight, Dawn Waterworth, H-Erich Wichmann, Gonneke Willemsen, Jacqueline C M Witteman, Xin Yuan, Jing Hua Zhao, Eleftheria Zeggini, David Schlessinger, Manjinder Sandhu, Dorret I Boomsma, Manuela Uda, Tim D Spector, Brenda WJH Penninx, David Altshuler, Peter Vollenweider, Marjo Riitta Jarvelin, Edward Lakatta, Gerard Waeber, Caroline S Fox, Leena Peltonen, Leif C Groop, Vincent Mooser, L Adrienne Cupples, Unnur Thorsteinsdottir, Michael Boehnke, Inês Barroso, Cornelia Van Duijn, Josée Dupuis, Richard M Watanabe, Kari Stefansson, Mark I McCarthy, Nicholas J Wareham, James B Meigs & Gonçalo R Abecasis

doi:10.1038/ng.290

Gonçalo Abecasis and colleagues report associations with fasting plasma glucose levels in a collection of ten genome–wide association scans from the MAGIC consortium. They find variants in the gene encoding melatonin receptor 1B that are associated with fasting glucose levels and, in a meta-analysis of 13 case-control studies, also show association with increased risk of type 2 diabetes.

First Paragraph - | Full Text - Variants in MTNR1B influence fasting glucose levels | PDF (346 KB) - Variants in MTNR1B influence fasting glucose levels | Supplementary information

Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion - pp82 - 88

Valeriya Lyssenko, Cecilia L F Nagorny, Michael R Erdos, Nils Wierup, Anna Jonsson, Peter Spégel, Marco Bugliani, Richa Saxena, Malin Fex, Nicolo Pulizzi, Bo Isomaa, Tiinamaija Tuomi, Peter Nilsson, Johanna Kuusisto, Jaakko Tuomilehto, Michael Boehnke, David Altshuler, Frank Sundler, Johan G Eriksson, Anne U Jackson, Markku Laakso, Piero Marchetti, Richard M Watanabe, Hindrik Mulder & Leif Groop

doi:10.1038/ng.288

Leif Groop and colleagues report that, in prospective studies, a variant in the gene encoding melantonin receptor 1B influences future risk of type 2 diabetes. Insulin release from pancreatic beta cells in response to glucose was inhibited by melatonin.

First Paragraph - | Full Text - Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion | PDF (424 KB) - Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion | Supplementary information

A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk - pp89 - 94

Nabila Bouatia-Naji, Amélie Bonnefond, Christine Cavalcanti-Proença, Thomas Sparsø, Johan Holmkvist, Marion Marchand, Jérôme Delplanque, Stéphane Lobbens, Ghislain Rocheleau, Emmanuelle Durand, Franck De Graeve, Jean-Claude Chèvre, Knut Borch-Johnsen, Anna-Liisa Hartikainen, Aimo Ruokonen, Jean Tichet, Michel Marre, Jacques Weill, Barbara Heude, Maithé Tauber, Katleen Lemaire, Frans Schuit, Paul Elliott, Torben Jørgensen, Guillaume Charpentier, Samy Hadjadj, Stéphane Cauchi, Martine Vaxillaire, Robert Sladek, Sophie Visvikis-Siest, Beverley Balkau, Claire Lévy-Marchal, François Pattou, David Meyre, Alexandra I F Blakemore, Marjo-Riita Jarvelin, Andrew J Walley, Torben Hansen, Christian Dina, Oluf Pedersen & Philippe Froguel

doi:10.1038/ng.277

Philippe Froguel and colleagues report an association of variants near the gene encoding melatonin receptor 2 with fasting glucose levels and risk of type 2 diabetes. The association suggests a possible link between circadian rhythm and glucose homeostasis.

First Paragraph - | Full Text - A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk | PDF (432 KB) - A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk | Supplementary information

Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis - pp95 - 100

Zandra A Jenkins, Margriet van Kogelenberg, Tim Morgan, Aaron Jeffs, Ryuji Fukuzawa, Esther Pearl, Christina Thaller, Anne V Hing, Mary E Porteous, Sixto Garcia-Miñaur, Axel Bohring, Didier Lacombe, Fiona Stewart, Torunn Fiskerstrand, Laurence Bindoff, Siren Berland, Lesley C Adès, Michel Tchan, Albert David, Louise C Wilson, Raoul C M Hennekam, Dian Donnai, Sahar Mansour, Valérie Cormier-Daire & Stephen P Robertson

doi:10.1038/ng.270

Stephen Robertson and colleagues report that germline mutations in WTX cause an X-linked sclerosing bone dysplasia marked by increased bone density and craniofacial malformations in females and lethality in males. In contrast with previous reports showing frequent somatic inactivation of WTX in Wilms tumor, individuals with germline WTX mutations are not predisposed to cancer.

First Paragraph - | Full Text - Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis | PDF (502 KB) - Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis | Supplementary information

Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2 - pp101 - 105

Ulrich Pannicke, Manfred Hönig, Isabell Hess, Claudia Friesen, Karlheinz Holzmann, Eva-Maria Rump, Thomas F Barth, Markus T Rojewski, Ansgar Schulz, Thomas Boehm, Wilhelm Friedrich & Klaus Schwarz

doi:10.1038/ng.265

Klaus Schwarz and colleagues report mutations in the gene encoding mitochondrial adenylate kinase 2 in reticular dysgenesis, the most severe form of inborn combined immunodeficiency, characterized by the absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood.

First Paragraph - | Full Text - Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2 | PDF (537 KB) - Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2 | Supplementary information

Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness - pp106 - 111

Chantal Lagresle-Peyrou, Emmanuelle M Six, Capucine Picard, Frédéric Rieux-Laucat, Vincent Michel, Andrea Ditadi, Corinne Demerens-de Chappedelaine, Estelle Morillon, Françoise Valensi, Karen L Simon-Stoos, James C Mullikin, Lenora M Noroski, Céline Besse, Nicolas M Wulffraat, Alina Ferster, Manuel M Abecasis, Fabien Calvo, Christine Petit, Fabio Candotti, Laurent Abel, Alain Fischer & Marina Cavazzana-Calvo

doi:10.1038/ng.278

Marina Cavazzana-Calvo and colleagues report mutations in the gene encoding mitochondrial adenylate kinase 2 in reticular dysgenesis, the most severe form of inborn combined immunodeficiency, characterized by the absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood.

First Paragraph - | Full Text - Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness | PDF (592 KB) - Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness | Supplementary information

Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1 - pp112 - 117

Marjolijn J L Ligtenberg, Roland P Kuiper, Tsun Leung Chan, Monique Goossens, Konnie M Hebeda, Marsha Voorendt, Tracy Y H Lee, Danielle Bodmer, Eveline Hoenselaar, Sandra J B Hendriks-Cornelissen, Wai Yin Tsui, Chi Kwan Kong, Han G Brunner, Ad Geurts van Kessel, Siu Tsan Yuen, J Han J M van Krieken, Suet Yi Leung & Nicoline Hoogerbrugge

doi:10.1038/ng.283

Marjolijn Ligtenberg and Suet Leung and colleagues report the identification of germline deletions in TACSTD1, a gene directly upstream of MSH2, in families with Lynch syndrome. The deletions result in transcriptional read-through of TACSTD1 into MSH2, and methylation and silencing of the MSH2 allele.

First Paragraph - | Full Text - Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1 | PDF (480 KB) - Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1 | Supplementary information

Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations - pp118 - 124

Nisha Limaye, Vinciane Wouters, Melanie Uebelhoer, Marjut Tuominen, Riikka Wirkkala, John B Mulliken, Lauri Eklund, Laurence M Boon & Miikka Vikkula

doi:10.1038/ng.272

Mikka Vikkula and colleagues report somatic mutations in the gene encoding the receptor tyrosine kinase TIE2 in inherited and common sporadic venous malformations. These mutations alter localization of the receptor and its response to ligand.

First Paragraph - | Full Text - Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations | PDF (1,090 KB) - Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations | Supplementary information

The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation - pp125 - 129

Jing Wang, Sarah Hevi, Julia K Kurash, Hong Lei, Frédérique Gay, Jeffrey Bajko, Hui Su, Weitao Sun, Hua Chang, Guoliang Xu, François Gaudet, En Li & Taiping Chen

doi:10.1038/ng.268

En Li and Taiping Chen and colleagues report that lysine specific demethylase 1 (LSD1, also known as AOF2) demethylates and stabilizes DNA methyltransferase 1 (Dnmt1), and that deletion of Aof2 in embryonic stem cells induces progressive loss of DNA methylation.

First Paragraph - | Full Text - The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation | PDF (549 KB) - The lysine demethylase LSD1 (KDM1) is required for maintenance of global DNA methylation | Supplementary information

See also: News and Views by Hotz & Peters

Tandem array–based expression screens identify host mRNA targets of virus-encoded microRNAs - pp130 - 134

Joseph M Ziegelbauer, Christopher S Sullivan & Don Ganem

doi:10.1038/ng.266

Donald Ganem and colleagues report a microarray-based approach to identify microRNA targets. They identify BCLAF1 as a target of miR-K5, a microRNA encoded by the Kaposi's sarcoma–associated herpesvirus.

First Paragraph - | Full Text - Tandem array–based expression screens identify host mRNA targets of virus-encoded microRNAs | PDF (409 KB) - Tandem array–based expression screens identify host mRNA targets of virus-encoded microRNAs | Supplementary information

See also: News and Views by Whitby