Modern lights - p265

doi:10.1038/ng0309-265

It's the year of Charles Darwin, with a variety of celebrations of his life and work ongoing. Educational outreach should emphasize the power of molecular and quantitative genetics to flesh out and build on Darwin's insights.

Abstract - | Full Text - Modern lights | PDF (142 KB) - Modern lights

In the aftermath of war - p267

Jay D. Aronson reviews To Know Where He Lies: DNA Technology and the Search for Srebrenica's Missing by Sarah Wagner

doi:10.1038/ng0309-267

Full Text - In the aftermath of war | PDF (153 KB) - In the aftermath of war

The neurokinin B pathway in human reproduction - pp269 - 270

Ana Claudia Latronico

doi:10.1038/ng0309-269

Studies of rare genetic disorders in humans have yielded important insights into the function of the hypothalamic-pituitary-gonadal axis. A new study now establishes a fundamental role for the neurokinin B pathway in normal reproductive function.

Abstract - | Full Text - The neurokinin B pathway in human reproduction | PDF (125 KB) - The neurokinin B pathway in human reproduction

See also: Letter by Topaloglu et al.

Processing the H3K36me3 signature - pp270 - 271

Robert J Sims III & Danny Reinberg

doi:10.1038/ng0309-270

The global patterning of histone lysine methylation has been scrutinized over the years in an effort to uncover unique features indicative of chromatin function. A study in Caenorhabditis elegans now shows that nucleosomes covering exons and introns on active genes are differentially marked by H3K36 trimethylation, suggesting a new mode of communication between chromatin and pre-mRNA processing.

Abstract - | Full Text - Processing the H3K36me3 signature | PDF (346 KB) - Processing the H3K36me3 signature

See also: Letter by Kolasinska-Zwierz et al.

FGF9 on the move - pp272 - 273

Douglas Spicer

doi:10.1038/ng0309-272

FGF receptors have been implicated in a number of syndromes that involve skeletal disorders. A new study in mice has identified a spontaneous mutation in Fgf9 with reduced activity but increased diffusion through tissues resulting in a gain-of-function phenotype comparable to those due to activating mutations in genes encoding FGF receptors.

Abstract - | Full Text - FGF9 on the move | PDF (515 KB) - FGF9 on the move

See also: Article by Harada et al.

Research Highlights - p275

doi:10.1038/ng0309-275

Full Text - Research Highlights | PDF (118 KB) - Research Highlights

Variant in the sequence of the LINGO1 gene confers risk of essential tremor - pp277 - 279

Hreinn Stefansson, Stacy Steinberg, Hjorvar Petursson, Omar Gustafsson, Iris H Gudjonsdottir, Gudrun A Jonsdottir, Stefan T Palsson, Thorlakur Jonsson, Jona Saemundsdottir, Gyda Bjornsdottir, Yvonne Böttcher, Theodora Thorlacius, Dietrich Haubenberger, Alexander Zimprich, Eduard Auff, Christoph Hotzy, Claudia M Testa, Lisa A Miyatake, Ami R Rosen, Kristleifur Kristleifsson, David Rye, Friedrich Asmus, Ludger Schöls, Martin Dichgans, Finnbogi Jakobsson, John Benedikz, Unnur Thorsteinsdottir, Jeffrey Gulcher, Augustine Kong & Kari Stefansson

doi:10.1038/ng.299

Kari Stefansson and colleagues report association of a variant in LINGO1 with risk of essential tremor, a common progressive neurological disease. Mice lacking Lingo1 have impaired axonal integrity, which may be relevant to the pathophysiology of the human disease.

Abstract - | Full Text - Variant in the sequence of the LINGO1 gene confers risk of essential tremor | PDF (222 KB) - Variant in the sequence of the LINGO1 gene confers risk of essential tremor | Supplementary information

New susceptibility locus for coronary artery disease on chromosome 3q22.3 - pp280 - 282

Jeanette Erdmann, Anika Grohennig, Peter S Braund, Inke R König, Christian Hengstenberg, Alistair S Hall, Patrick Linsel-Nitschke, Sekar Kathiresan, Ben Wright, David-Alexandre Trégouët, Francois Cambien, Petra Bruse, Zouhair Aherrahrou, Arnika K Wagner, Klaus Stark, Stephen M Schwartz, Veikko Salomaa, Roberto Elosua, Olle Melander, Benjamin F Voight, Christopher J O'Donnell, Leena Peltonen, David S Siscovick, David Altshuler, Piera Angelica Merlini, Flora Peyvandi, Luisa Bernardinelli, Diego Ardissino, Arne Schillert, Stefan Blankenberg, Tanja Zeller, Philipp Wild, Daniel F Schwarz, Laurence Tiret, Claire Perret, Stefan Schreiber, Nour Eddine El Mokhtari, Arne Schäfer, Winfried März, Wilfried Renner, Peter Bugert, Harald Klüter, Jürgen Schrezenmeir, Diana Rubin, Stephen G Ball, Anthony J Balmforth, H-Erich Wichmann, Thomas Meitinger, Marcus Fischer, Christa Meisinger, Jens Baumert, Annette Peters, Willem H Ouwehand, Italian Atherosclerosis, Thrombosis, and Vascular Biology Working Group, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Cardiogenics Consortium, Panos Deloukas, John R Thompson, Andreas Ziegler, Nilesh J Samani & Heribert Schunkert

doi:10.1038/ng.307

Jeanette Erdmann and colleagues identify a locus on chromosome 3q22.3 associated with coronary artery disease. The SNP with the strongest association is in MRAS, which encodes a membrane-anchored GTP-binding protein.

Abstract - | Full Text - New susceptibility locus for coronary artery disease on chromosome 3q22.3 | PDF (248 KB) - New susceptibility locus for coronary artery disease on chromosome 3q22.3 | Supplementary information

Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease - pp283 - 285

David-Alexandre Trégouët, Inke R König, Jeanette Erdmann, Alexandru Munteanu, Peter S Braund, Alistair S Hall, Anika Grohennig, Patrick Linsel-Nitschke, Claire Perret, Maylis DeSuremain, Thomas Meitinger, Ben J Wright, Michael Preuss, Anthony J Balmforth, Stephen G Ball, Christa Meisinger, Cécile Germain, Alun Evans, Dominique Arveiler, Gérald Luc, Jean-Bernard Ruidavets, Caroline Morrison, Pim van der Harst, Stefan Schreiber, Katharina Neureuther, Arne Schäfer, Peter Bugert, Nour E El Mokhtari, Jürgen Schrezenmeir, Klaus Stark, Diana Rubin, H-Erich Wichmann, Christian Hengstenberg, Willem Ouwehand, Wellcome Trust Case Control Consortium, Cardiogenics Consortium, Andreas Ziegler, Laurence Tiret, John R Thompson, Francois Cambien, Heribert Schunkert & Nilesh J Samani

doi:10.1038/ng.314

Using a haplotype-based approach, David-Alexandre Trégouët and colleagues report that the SLC22A3-LPAL2-LPA gene cluster is associated with risk of coronary artery disease.

Abstract - | Full Text - Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease | PDF (218 KB) - Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease | Supplementary information

Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia - pp286 - 288

Tania Fuchs, Sophie Gavarini, Rachel Saunders-Pullman, Deborah Raymond, Michelle E Ehrlich, Susan B Bressman & Laurie J Ozelius

doi:10.1038/ng.304

Laurie Ozelius and colleagues identify mutations in THAP1 in families with a mixed type (DYT6) of primary torsion dystonia, a movement disorder characterized by twisting movements and abnormal posture.

Abstract - | Full Text - Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia | PDF (264 KB) - Mutations in the THAP1 gene are responsible for DYT6 primary torsion dystonia | Supplementary information

FGF9 monomer–dimer equilibrium regulates extracellular matrix affinity and tissue diffusion - pp289 - 298

Masayo Harada, Hirotaka Murakami, Akihiko Okawa, Noriaki Okimoto, Shuichi Hiraoka, Taka Nakahara, Ryogo Akasaka, Yo-ichi Shiraishi, Noriyuki Futatsugi, Yoko Mizutani-Koseki, Atsushi Kuroiwa, Mikako Shirouzu, Shigeyuki Yokoyama, Makoto Taiji, Sachiko Iseki, David M Ornitz & Haruhiko Koseki

doi:10.1038/ng.316

Haruhiko Koseki and colleagues identify a gain-of-function mutation in Fgf9 in mice with elbow knee synostosis. They further show that this mutation prevents homodimerization of Fgf9, allowing increased diffusion of the altered protein through developing tissues.

Abstract - | Full Text - FGF9 monomer–dimer equilibrium regulates extracellular matrix affinity and tissue diffusion | PDF (2,580 KB) - FGF9 monomer–dimer equilibrium regulates extracellular matrix affinity and tissue diffusion | Supplementary information

See also: News and Views by Spicer

Systems genetics of complex traits in Drosophila melanogaster - pp299 - 307

Julien F Ayroles, Mary Anna Carbone, Eric A Stone, Katherine W Jordan, Richard F Lyman, Michael M Magwire, Stephanie M Rollmann, Laura H Duncan, Faye Lawrence, Robert R H Anholt & Trudy F C Mackay

doi:10.1038/ng.332

Trudy Mackay and colleagues present a resource of 40 Drosophila melanogaster wild-derived inbred lines. The authors quantify genome-wide variation in transcript abundance for six ecologically relevant traits, characterize the transcriptome and identify transcriptional modules.

Abstract - | Full Text - Systems genetics of complex traits in Drosophila melanogaster | PDF (4,064 KB) - Systems genetics of complex traits in Drosophila melanogaster | Supplementary information

-Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity - pp308 - 315

Aaron D Gitler, Alessandra Chesi, Melissa L Geddie, Katherine E Strathearn, Shusei Hamamichi, Kathryn J Hill, Kim A Caldwell, Guy A Caldwell, Antony A Cooper, Jean-Christophe Rochet & Susan Lindquist

doi:10.1038/ng.300

Susan Lindquist and colleagues report a genetic interaction between -synuclein and the ortholog of human ATP13A2 (PARK9) in yeast, two genes that when mutated cause Parkinson's disease. They further show that yeast PARK9 protects cells from manganese toxicity, a known environmental risk factor for Parkinson's disease.

Abstract - | Full Text - -Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity | PDF (647 KB) - -Synuclein is part of a diverse and highly conserved interaction network that includes PARK9 and manganese toxicity | Supplementary information

Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity - pp316 - 323

Esti Yeger-Lotem, Laura Riva, Linhui Julie Su, Aaron D Gitler, Anil G Cashikar, Oliver D King, Pavan K Auluck, Melissa L Geddie, Julie S Valastyan, David R Karger, Susan Lindquist & Ernest Fraenkel

doi:10.1038/ng.337

Ernest Fraenkel and colleagues present ResponseNet, a method used to integrate analysis of genetic and transcriptional datasets, and its application characterizing yeast cellular responses to alpha-synuclein toxicity.

Abstract - | Full Text - Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity | PDF (1,135 KB) - Bridging high-throughput genetic and transcriptional data reveals cellular responses to alpha-synuclein toxicity | Supplementary information

Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1 - pp324 - 328

Wei Zheng, Jirong Long, Yu-Tang Gao, Chun Li, Ying Zheng, Yong-Bin Xiang, Wanqing Wen, Shawn Levy, Sandra L Deming, Jonathan L Haines, Kai Gu, Alecia Malin Fair, Qiuyin Cai, Wei Lu & Xiao-Ou Shu

doi:10.1038/ng.318

Wei Zheng and colleagues carried out a genome-wide association study of breast cancer in Chinese women and discovered risk variants on 6q25.1 located upstream of the gene encoding estrogen receptor 1 (ESR1). They also found a similar association between the 6q25.1 locus and breast cancer in samples of European ancestry.

First Paragraph - | Full Text - Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1 | PDF (371 KB) - Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1 | Supplementary information

SNPs in BRAP associated with risk of myocardial infarction in Asian populations - pp329 - 333

Kouichi Ozaki, Hiroshi Sato, Katsumi Inoue, Tatsuhiko Tsunoda, Yasuhiko Sakata, Hiroya Mizuno, Tsung-Hsien Lin, Yoshinari Miyamoto, Asako Aoki, Yoshihiro Onouchi, Sheng-Hsiung Sheu, Shiro Ikegawa, Keita Odashiro, Masakiyo Nobuyoshi, Suh-Hang H Juo, Masatsugu Hori, Yusuke Nakamura & Toshihiro Tanaka

doi:10.1038/ng.326

Toshihiro Tanaka and colleagues report the identification of variants in BRAP, which encodes a galectin-2–binding protein, that are associated with risk of myocardial infarction in two Asian populations.

First Paragraph - | Full Text - SNPs in BRAP associated with risk of myocardial infarction in Asian populations | PDF (424 KB) - SNPs in BRAP associated with risk of myocardial infarction in Asian populations | Supplementary information

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants - pp334 - 341

Myocardial Infarction Genetics Consortium

doi:10.1038/ng.327

The Myocardial Infarction Genetics Consortium reports results of a genome-wide association study of early-onset myocardial infarction. The study analyzed common SNPs, common CNVs and rare CNVs and identified SNP alleles at three new loci associated with disease risk.

First Paragraph - | Full Text - Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants | PDF (351 KB) - Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants | Supplementary information

Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction - pp342 - 347

Daniel F Gudbjartsson, Unnur S Bjornsdottir, Eva Halapi, Anna Helgadottir, Patrick Sulem, Gudrun M Jonsdottir, Gudmar Thorleifsson, Hafdis Helgadottir, Valgerdur Steinthorsdottir, Hreinn Stefansson, Carolyn Williams, Jennie Hui, John Beilby, Nicole M Warrington, Alan James, Lyle J Palmer, Gerard H Koppelman, Andrea Heinzmann, Marcus Krueger, H Marike Boezen, Amanda Wheatley, Janine Altmuller, Hyoung Doo Shin, Soo-Taek Uh, Hyun Sub Cheong, Brynja Jonsdottir, David Gislason, Choon-Sik Park, Linda M Rasmussen, Celeste Porsbjerg, Jakob W Hansen, Vibeke Backer, Thomas Werge, Christer Janson, Ulla-Britt Jönsson, Maggie C Y Ng, Juliana Chan, Wing Yee So, Ronald Ma, Svati H Shah, Christopher B Granger, Arshed A Quyyumi, Allan I Levey, Viola Vaccarino, Muredach P Reilly, Daniel J Rader, Michael J A Williams, Andre M van Rij, Gregory T Jones, Elisabetta Trabetti, Giovanni Malerba, Pier Franco Pignatti, Attilio Boner, Lydia Pescollderungg, Domenico Girelli, Oliviero Olivieri, Nicola Martinelli, Bjorn R Ludviksson, Dora Ludviksdottir, Gudmundur I Eyjolfsson, David Arnar, Gudmundur Thorgeirsson, Klaus Deichmann, Philip J Thompson, Matthias Wjst, Ian P Hall, Dirkje S Postma, Thorarinn Gislason, Jeffrey Gulcher, Augustine Kong, Ingileif Jonsdottir, Unnur Thorsteinsdottir & Kari Stefansson

doi:10.1038/ng.323

Daniel Gudbjartsson and colleagues report results of a genome-wide association study for loci influencing eosinophil counts. Follow-up studies showed that a subset of the variants identified in this screen were associated with risk of asthma or myocardial infarction.

First Paragraph - | Full Text - Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction | PDF (307 KB) - Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction | Supplementary information

Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure - pp348 - 353

Christopher Newton-Cheh, Martin G Larson, Ramachandran S Vasan, Daniel Levy, Kenneth D Bloch, Aarti Surti, Candace Guiducci, Sekar Kathiresan, Emelia J Benjamin, Joachim Struck, Nils G Morgenthaler, Andreas Bergmann, Stefan Blankenberg, Frank Kee, Peter Nilsson, Xiaoyan Yin, Leena Peltonen, Erkki Vartiainen, Veikko Salomaa, Joel N Hirschhorn, Olle Melander & Thomas J Wang

doi:10.1038/ng.328

Christopher Newton-Cheh and colleagues report the identification of common variants at the NPPA-NPPB locus associated with plasma atrial natriuretic peptide concentration, as well as with lower systolic and diastolic blood pressure, and reduced risk of hypertension.

First Paragraph - | Full Text - Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure | PDF (520 KB) - Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure | Supplementary information

TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction - pp354 - 358

A Kemal Topaloglu, Frank Reimann, Metin Guclu, Ayse Serap Yalin, L Damla Kotan, Keith M Porter, Ayse Serin, Neslihan O Mungan, Joshua R Cook, Mehmet N Ozbek, Sazi Imamoglu, N Sema Akalin, Bilgin Yuksel, Stephen O'Rahilly & Robert K Semple

doi:10.1038/ng.306

A. Kemal Topaloglu and colleagues report the identification of mutations in the neurokinin B receptor and its ligand in families with severe congenital gonadotropin deficiency and pubertal failure. These findings indicate that neurokinin B is a central regulator of human gonadal function.

First Paragraph - | Full Text - TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction | PDF (1,123 KB) - TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction | Supplementary information

See also: News and Views by Latronico

Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence - pp359 - 364

Sabina Benko, Judy A Fantes, Jeanne Amiel, Dirk-Jan Kleinjan, Sophie Thomas, Jacqueline Ramsay, Negar Jamshidi, Abdelkader Essafi, Simon Heaney, Christopher T Gordon, David McBride, Christelle Golzio, Malcolm Fisher, Paul Perry, Véronique Abadie, Carmen Ayuso, Muriel Holder-Espinasse, Nicky Kilpatrick, Melissa M Lees, Arnaud Picard, I Karen Temple, Paul Thomas, Marie-Paule Vazquez, Michel Vekemans, Hugues Roest Crollius, Nicholas D Hastie, Arnold Munnich, Heather C Etchevers, Anna Pelet, Peter G Farlie, David R FitzPatrick & Stanislas Lyonnet

doi:10.1038/ng.329

Stanislas Lyonnet and colleagues report a new locus associated with Pierre Robin sequence, an important subgroup of cleft palate. They find that translocations, deletions and point mutation affecting highly conserved noncoding elements (HCNEs) found at distances on either side of SOX9 are associated with PRS.

First Paragraph - | Full Text - Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence | PDF (569 KB) - Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence | Supplementary information

A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function - pp365 - 370

Sonia A Melo, Santiago Ropero, Catia Moutinho, Lauri A Aaltonen, Hiroyuki Yamamoto, George A Calin, Simona Rossi, Agustin F Fernandez, Fatima Carneiro, Carla Oliveira, Bibiana Ferreira, Chang-Gong Liu, Alberto Villanueva, Gabriel Capella, Simo Schwartz Jr, Ramin Shiekhattar & Manel Esteller

doi:10.1038/ng.317

Manel Esteller and colleagues report truncating mutations in TARBP2, an integral component of a DICER1-containing complex, in human colorectal cancers. This is the first report of a mutation in one of the genes involved in miRNA processing in human cancer.

First Paragraph - | Full Text - A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function | PDF (529 KB) - A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function | Supplementary information

Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep - pp371 - 375

Susan T Harbison, Mary Anna Carbone, Julien F Ayroles, Eric A Stone, Richard F Lyman & Trudy F C Mackay

doi:10.1038/ng.330

Trudy Mackay and colleagues measure sleep phenotypes in 40 wild-derived Drosophila lines, and report candidate genes and transcriptional networks associated with sleep regulation.

First Paragraph - | Full Text - Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep | PDF (585 KB) - Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep | Supplementary information

Differential chromatin marking of introns and expressed exons by H3K36me3 - pp376 - 381

Paulina Kolasinska-Zwierz, Thomas Down, Isabel Latorre, Tao Liu, X Shirley Liu & Julie Ahringer

doi:10.1038/ng.322

Julie Ahringer and colleagues show that, in C. elegans, exons are preferentially marked with H3K36me3 relative to introns, and that the difference in H3K36me3 marking between exons and introns is evolutionarily conserved in human and mouse.

First Paragraph - | Full Text - Differential chromatin marking of introns and expressed exons by H3K36me3 | PDF (1,040 KB) - Differential chromatin marking of introns and expressed exons by H3K36me3 | Supplementary information

See also: News and Views by Sims III & Reinberg