From risk to function - p929

doi:10.1038/ng0808-929

In association with the Wellcome Trust, we are pleased to announce the second Genomics of Common Diseases conference to be held September 6–9, 2008, in Cambridge, MA, USA.

Abstract - | Full Text - From risk to function | PDF (143 KB) - From risk to function

Famed biologist lost to Stalin's terror - p930

Vadim Birstein reviews The Murder of Nikolai Vavilov: The Story of Stalin's Persecution of One of the Great Scientists of the Twentieth Century by Peter Pringle

doi:10.1038/ng0808-930

Full Text - Famed biologist lost to Stalin's terror | PDF (157 KB) - Famed biologist lost to Stalin's terror

Dark skin mutations shed light on inherited anemia - pp931 - 932

Philip J Mason & Monica Bessler

doi:10.1038/ng0808-931

A new study of pigmentation in mice has revealed a surprising link between dark skin and defects in ribosomal proteins. The demonstration that this phenotype is mediated via cell-specific stabilization of p53 suggests insights into the pathogenesis of human diseases such as Diamond-Blackfan anemia caused by similar defects in ribosomal proteins.

Abstract - | Full Text - Dark skin mutations shed light on inherited anemia | PDF (160 KB) - Dark skin mutations shed light on inherited anemia

See also: Article by McGowan et al.

H19 in the pouch - pp932 - 933

Marisa S Bartolomei, Sebastien Vigneau & Michael J O'Neill

doi:10.1038/ng0808-932

The linked maternally expressed H19 and paternally expressed Igf2 genes use a CTCF-dependent DNA methylation–sensitive insulator to govern their allele-specific imprinting patterns. Contrary to expectations, a new study shows that the noncoding H19 RNA has a marsupial ortholog and that key features of the locus are similar, indicating that the imprinting regulation of this locus is conserved among therian mammals.

Abstract - | Full Text - H19 in the pouch | PDF (245 KB) - H19 in the pouch

See also: Article by Smits et al.

One PRDM is not enough for germ cell development - pp934 - 935

Elizabeth K Bikoff & Elizabeth J Robertson

doi:10.1038/ng0808-934

Developmentally regulated expression of the transcriptional repressor Prdm1 (Blimp1) in the early mammalian embryo controls global epigenetic changes required for specification of primordial germ cells. A new study demonstrates that a close family member, Prdm14, similarly activated in response to Bmp and Smad signals, also has an essential role during establishment of the germ cell lineage.

Abstract - | Full Text - One PRDM is not enough for germ cell development | PDF (381 KB) - One PRDM is not enough for germ cell development

See also: Letter by Yamaji et al.

Mapping the strand-specific transcriptome of fission yeast - pp935 - 936

Thomas R Gingeras

doi:10.1038/ng0808-935

Pervasive genome-wide transcription is widespread in eukaryotic cells, but key features of the transcriptome have yet to be fully characterized. A new study using antibody-based detection of RNA-DNA duplexes on tiling arrays now reveals a complex, strand-specific transcriptional world in fission yeast.

Abstract - | Full Text - Mapping the strand-specific transcriptome of fission yeast | PDF (399 KB) - Mapping the strand-specific transcriptome of fission yeast

See also: Article by Dutrow et al.

Research highlights - p937

doi:10.1038/ng0808-937

Full Text - Research highlights | PDF (121 KB) - Research highlights

Putting science over supposition in the arena of personalized genomics - pp939 - 942

Colleen M McBride, Sharon Hensley Alford, Robert J Reid, Eric B Larson, Andreas D Baxevanis & Lawrence C Brody

doi:10.1038/ng0808-939

Colleen McBride and colleagues argue that progress on a multifaceted research agenda is necessary to reap the full benefits and avoid the potential pitfalls of the emerging area of personalized genomics. They also outline one element of this agenda, the Multiplex Initiative, which has been underway since 2006.

Abstract - | Full Text - Putting science over supposition in the arena of personalized genomics | PDF (195 KB) - Putting science over supposition in the arena of personalized genomics

Common nonsynonymous variants in PCSK1 confer risk of obesity - pp943 - 945

Michael Benzinou, John W M Creemers, Helene Choquet, Stephane Lobbens, Christian Dina, Emmanuelle Durand, Audrey Guerardel, Philippe Boutin, Beatrice Jouret, Barbara Heude, Beverley Balkau, Jean Tichet, Michel Marre, Natascha Potoczna, Fritz Horber, Catherine Le Stunff, Sebastien Czernichow, Annelli Sandbaek, Torsten Lauritzen, Knut Borch-Johnsen, Gitte Andersen, Wieland Kiess, Antje Körner, Peter Kovacs, Peter Jacobson, Lena M S Carlsson, Andrew J Walley, Torben Jørgensen, Torben Hansen, Oluf Pedersen, David Meyre & Philippe Froguel

doi:10.1038/ng.177

Philippe Froguel and colleagues report that common nonsynonymous variants in PCSK1, encoding a prohormone convertase, confer risk of obesity in individuals of European ancestry.

Abstract - | Full Text - Common nonsynonymous variants in PCSK1 confer risk of obesity | PDF (241 KB) - Common nonsynonymous variants in PCSK1 confer risk of obesity | Supplementary information

PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome - pp946 - 948

Barbara Schormair, David Kemlink, Darina Roeske, Gertrud Eckstein, Lan Xiong, Peter Lichtner, Stephan Ripke, Claudia Trenkwalder, Alexander Zimprich, Karin Stiasny-Kolster, Wolfgang Oertel, Cornelius G Bachmann, Walter Paulus, Birgit Högl, Birgit Frauscher, Viola Gschliesser, Werner Poewe, Ines Peglau, Pavel Vodicka, Jana Vávrová, Karel Sonka, Sona Nevsimalova, Jacques Montplaisir, Gustavo Turecki, Guy Rouleau, Christian Gieger, Thomas Illig, H-Erich Wichmann, Florian Holsboer, Bertram Müller-Myhsok, Thomas Meitinger & Juliane Winkelmann

doi:10.1038/ng.190

Juliane Winkelmann and colleagues report that two common variants in the 5' UTR of PTPRD are independently associated with restless legs syndrome. PTPRD encodes a receptor-like protein tyrosine phosphatase previously implicated in axon guidance and motor neuron development.

Abstract - | Full Text - PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome | PDF (277 KB) - PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome | Supplementary information

Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57 - pp949 - 951

Deborah J G Mackay, Jonathan L A Callaway, Sophie M Marks, Helen E White, Carlo L Acerini, Susanne E Boonen, Pinar Dayanikli, Helen V Firth, Judith A Goodship, Andreas P Haemers, Johanne M D Hahnemann, Olga Kordonouri, Ahmed F Masoud, Elsebet Oestergaard, John Storr, Sian Ellard, Andrew T Hattersley, David O Robinson & I Karen Temple

doi:10.1038/ng.187

Deborah Mackay and colleagues identify mutations in ZFP57, encoding a zinc-finger transcription factor, in families with transient neonatal diabetes and additional clinical features. Affected individuals have a variable pattern of DNA hypomethylation at multiple imprinted loci.

Abstract - | Full Text - Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57 | PDF (733 KB) - Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57 | Supplementary information

Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension - pp952 - 954

Michal Pravenec, Paul C Churchill, Monique C Churchill, Ondrej Viklicky, Ludmila Kazdova, Timothy J Aitman, Enrico Petretto, Norbert Hubner, Caroline A Wallace, Heike Zimdahl, Vaclav Zidek, Vladimir Landa, Joseph Dunbar, Anil Bidani, Karen Griffin, Nathan Qi, Martina Maxova, Vladimir Kren, Petr Mlejnek, Jiaming Wang & Theodore W Kurtz

doi:10.1038/ng.164

Theodore Kurtz and colleagues report that Cd36 expression in the kidney underlies a quantitative trait locus for essential hypertension in the rat. Cd36 affects levels of cyclic GMP, a downstream effector of nitric oxide signaling, consistent with published data that reduced nitric oxide activity in the kidney is associated with hypertension.

Abstract - | Full Text - Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension | PDF (291 KB) - Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension | Supplementary information

Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease - pp955 - 962

Jeffrey C Barrett, Sarah Hansoul, Dan L Nicolae, Judy H Cho, Richard H Duerr, John D Rioux, Steven R Brant, Mark S Silverberg, Kent D Taylor, M Michael Barmada, Alain Bitton, Themistocles Dassopoulos, Lisa Wu Datta, Todd Green, Anne M Griffiths, Emily O Kistner, Michael T Murtha, Miguel D Regueiro, Jerome I Rotter, L Philip Schumm, A Hillary Steinhart, Stephan R Targan, Ramnik J Xavier, the NIDDK IBD Genetics Consortium, Cécile Libioulle, Cynthia Sandor, Mark Lathrop, Jacques Belaiche, Olivier Dewit, Ivo Gut, Simon Heath, Debby Laukens, Myriam Mni, Paul Rutgeerts, André Van Gossum, Diana Zelenika, Denis Franchimont, Jean-Pierre Hugot, Martine de Vos, Severine Vermeire, Edouard Louis, the Belgian-French IBD Consortium, the Wellcome Trust Case Control Consortium, Lon R Cardon, Carl A Anderson, Hazel Drummond, Elaine Nimmo, Tariq Ahmad, Natalie J Prescott, Clive M Onnie, Sheila A Fisher, Jonathan Marchini, Jilur Ghori, Suzannah Bumpstead, Rhian Gwilliam, Mark Tremelling, Panos Deloukas, John Mansfield, Derek Jewell, Jack Satsangi, Christopher G Mathew, Miles Parkes, Michel Georges & Mark J Daly

doi:10.1038/ng.175

Mark Daly and colleagues present results of a combined analysis of data from three recent genome-wide association studies for Crohn's disease, followed by replication in a large independent sample collection. Their results confirm 11 previously reported risk loci and provide genome-wide significant evidence for 21 new loci associated with the disease.

Abstract - | Full Text - Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease | PDF (704 KB) - Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease | Supplementary information

Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects - pp963 - 970

Kelly A McGowan, Jun Z Li, Christopher Y Park, Veronica Beaudry, Holly K Tabor, Amit J Sabnis, Weibin Zhang, Helmut Fuchs, Martin Hrabé de Angelis, Richard M Myers, Laura D Attardi & Gregory S Barsh

doi:10.1038/ng.188

Greg Barsh and colleagues show that two loci for dark skin in mice result from mutations in Rps19 and Rps20, encoding the ribosomal proteins S19 and S20. They further show that the dark skin phenotype and other pleiotropic effects of these mutations, including reduced erythrocyte count and body size, are mediated through stabilization of p53.

Abstract - | Full Text - Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects | PDF (715 KB) - Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects | Supplementary information

See also: News and Views by Mason & Bessler

Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians - pp971 - 976

Guillaume Smits, Andrew J Mungall, Sam Griffiths-Jones, Paul Smith, Delphine Beury, Lucy Matthews, Jane Rogers, Andrew J Pask, Geoff Shaw, John L VandeBerg, John R McCarrey, the SAVOIR Consortium, Marilyn B Renfree, Wolf Reik & Ian Dunham

doi:10.1038/ng.168

Wolf Reik and Ian Dunham and colleagues cloned and sequenced the complete IGF2-H19 locus in tammar wallaby, a marsupial. Functional analyses revealed conservation of imprinting mechanisms, including germline DNA methylation, between marsupials and eutherians.

Abstract - | Full Text - Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians | PDF (617 KB) - Conservation of the H19 noncoding RNA and H19-IGF2 imprinting mechanism in therians | Supplementary information

See also: News and Views by Bartolomei et al.

Dynamic transcriptome of Schizosaccharomyces pombe shown by RNA-DNA hybrid mapping - pp977 - 986

Natalie Dutrow, David A Nix, Derick Holt, Brett Milash, Brian Dalley, Erick Westbroek, Timothy J Parnell & Bradley R Cairns

doi:10.1038/ng.196

Bradley Cairns and colleagues report a high-resolution strand-specific transcriptome of the fission yeast Schizosaccharomyces pombe. They survey the transcriptome under multiple growth conditions using an RNA-DNA hybridization mapping (HybMap) technique, and find that most of the euchromatic genome is transcribed.

Abstract - | Full Text - Dynamic transcriptome of Schizosaccharomyces pombe shown by RNA-DNA hybrid mapping | PDF (874 KB) - Dynamic transcriptome of Schizosaccharomyces pombe shown by RNA-DNA hybrid mapping | Supplementary information

See also: News and Views by Gingeras

High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi - pp987 - 993

Kathryn E Holt, Julian Parkhill, Camila J Mazzoni, Philippe Roumagnac, François-Xavier Weill, Ian Goodhead, Richard Rance, Stephen Baker, Duncan J Maskell, John Wain, Christiane Dolecek, Mark Achtman & Gordon Dougan

doi:10.1038/ng.195

Isolates of Salmonella enterica serovar Typhi (Typhi), a human-restricted bacterial pathogen that causes typhoid, show limited genetic variation. Kathryn Holt and colleagues now compare whole-genome sequences of 19 Typhi isolates dispersed throughout the phylogenetic tree of this pathogen, revealing notably little evidence of purifying selection, antigenic variation or recombination between isolates.

Abstract - | Full Text - High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi | PDF (332 KB) - High-throughput sequencing provides insights into genome variation and evolution in Salmonella Typhi | Supplementary information

Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis - pp994 - 998

Yoshinari Miyamoto, Dongquan Shi, Masahiro Nakajima, Kouichi Ozaki, Akihiro Sudo, Akihiro Kotani, Atsumasa Uchida, Toshihiro Tanaka, Naoshi Fukui, Tatsuhiko Tsunoda, Atsushi Takahashi, Yusuke Nakamura, Qing Jiang & Shiro Ikegawa

doi:10.1038/ng.176

Shiro Ikegawa and colleagues identify a variant in a newly identified gene, DVWA, that is associated with susceptibility to knee osteoarthritis. DVWA contains von Willebrand factor domains and is expressed specifically in cartilage.

First Paragraph - | Full Text - Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis | PDF (257 KB) - Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis | Supplementary information

Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia - pp999 - 1003

Matthew J Rock, Jean Prenen, Vincent A Funari, Tara L Funari, Barry Merriman, Stanley F Nelson, Ralph S Lachman, William R Wilcox, Soraya Reyno, Roberto Quadrelli, Alicia Vaglio, Grzegorz Owsianik, Annelies Janssens, Thomas Voets, Shiro Ikegawa, Toshiro Nagai, David L Rimoin, Bernd Nilius & Daniel H Cohn

doi:10.1038/ng.166

Daniel Cohn and colleagues identify mutations in the gene encoding the calcium-permeable cation channel TRPV4 in families with autosomal dominant brachyolmia. Functional studies show that the mutations result in gain-of-function of channel activation.

First Paragraph - | Full Text - Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia | PDF (396 KB) - Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia | Supplementary information

A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse - pp1004 - 1009

Gerli Rosengren Pielberg, Anna Golovko, Elisabeth Sundström, Ino Curik, Johan Lennartsson, Monika H Seltenhammer, Thomas Druml, Matthew Binns, Carolyn Fitzsimmons, Gabriella Lindgren, Kaj Sandberg, Roswitha Baumung, Monika Vetterlein, Sara Strömberg, Manfred Grabherr, Claire Wade, Kerstin Lindblad-Toh, Fredrik Pontén, Carl-Henrik Heldin, Johann Sölkner & Leif Andersson

doi:10.1038/ng.185

Gray horses are born colored but gradually lose hair pigmentation and become white, a trait that is transmitted in an autosomal dominant manner. Leif Andersson and colleagues report that the the mutation causing the Gray phenotype is a 4.6-kb duplication in intron 6 of STX17, which promotes overexpression of both STX17 and the neighboring gene NR4A3 in melanomas from Gray horses.

First Paragraph - | Full Text - A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse | PDF (534 KB) - A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse | Supplementary information

Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease - pp1010 - 1015

Sakura Saburi, Ian Hester, Evelyne Fischer, Marco Pontoglio, Vera Eremina, Manfred Gessler, Sue E Quaggin, Robert Harrison, Richard Mount & Helen McNeill

doi:10.1038/ng.179

Helen McNeill and colleagues show that loss of Fat4, a homolog of the Drosophila planar cell polarity protein Fat, disrupts oriented cell division, leading to a failure of tubule elongation and cystic kidney disease in mice. The findings suggest that loss of planar cell polarity may underlie some forms of cystic kidney disease in humans.

First Paragraph - | Full Text - Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease | PDF (985 KB) - Loss of Fat4 disrupts PCP signaling and oriented cell division and leads to cystic kidney disease | Supplementary information

Critical function of Prdm14 for the establishment of the germ cell lineage in mice - pp1016 - 1022

Masashi Yamaji, Yoshiyuki Seki, Kazuki Kurimoto, Yukihiro Yabuta, Mihoko Yuasa, Mayo Shigeta, Kaori Yamanaka, Yasuhide Ohinata & Mitinori Saitou

doi:10.1038/ng.186

Mitinori Saitou and colleagues report that Prdm14, which encodes a transcription factor expressed exclusively in the germ cell lineage, is essential for re-acquisition of pluripotency and epigenetic reprogramming of primordial germ cells.

First Paragraph - | Full Text - Critical function of Prdm14 for the establishment of the germ cell lineage in mice | PDF (982 KB) - Critical function of Prdm14 for the establishment of the germ cell lineage in mice | Supplementary information

See also: News and Views by Bikoff & Robertson

Deletion in a gene associated with grain size increased yields during rice domestication - pp1023 - 1028

Ayahiko Shomura, Takeshi Izawa, Kaworu Ebana, Takeshi Ebitani, Hiromi Kanegae, Saeko Konishi & Masahiro Yano

doi:10.1038/ng.169

Takeshi Izawa and colleagues report the cloning of a gene underlying a rice quantitative trait locus influencing grain width. A deletion in qSW5 increases yield of rice grains, and the authors show that this mutation has likely been selected for during the domestication of rice.

First Paragraph - | Full Text - Deletion in a gene associated with grain size increased yields during rice domestication | PDF (551 KB) - Deletion in a gene associated with grain size increased yields during rice domestication | Supplementary information

Corrigendum: ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma - p1029

Daniel F Gudbjartsson, Patrick Sulem, Simon N Stacey, Alisa M Goldstein, Thorunn Rafnar, Bardur Sigurgeirsson, Kristrun R Benediktsdottir, Kristin Thorisdottir, Rafn Ragnarsson, Steinunn G Sveinsdottir, Veronica Magnusson, Annika Lindblom, Konstantinos Kostulas, Rafael Botella-Estrada, Virtudes Soriano, Pablo Juberías, Matilde Grasa, Berta Saez, Raquel Andres, Dominique Scherer, Peter Rudnai, Eugene Gurzau, Kvetoslava Koppova, Lambertus A Kiemeney, Margret Jakobsdottir, Stacy Steinberg, Agnar Helgason, Solveig Gretarsdottir, Margaret A Tucker, José I Mayordomo, Eduardo Nagore, Rajiv Kumar, Johan Hansson, Jon H Olafsson, Jeffrey Gulcher, Augustine Kong, Unnur Thorsteinsdottir & Kari Stefansson

doi:10.1038/ng0808-1029

Full Text - Corrigendum: ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma | PDF (75 KB) - Corrigendum: ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma