Back to basics in Berlin - p1031

doi:10.1038/ng0908-1031

At this year's quinquennial International Congress of Genetics, human genetics provided only a fascinating minority of the content of this conference dedicated to illuminating fundamental biological systems and their evolution.

Abstract - | Full Text - Back to basics in Berlin | PDF (150 KB) - Back to basics in Berlin

Variation in KLK genes, prostate-specific antigen and risk of prostate cancer - pp1032 - 1034

Jiyoung Ahn, Sonja I Berndt, Sholom Wacholder, Peter Kraft, Adam S Kibel, Meredith Yeager, Demetrius Albanes, Edward Giovannucci, Meir J Stampfer, Jarmo Virtamo, Michael J Thun, Heather Spencer Feigelson, Geraldine Cancel-Tassin, Olivier Cussenot, Gilles Thomas, David J Hunter, Joseph F Fraumeni Jr., Robert N Hoover, Stephen J Chanock & Richard B Hayes

doi:10.1038/ng0908-1032

Full Text - Variation in KLK genes, prostate-specific antigen and risk of prostate cancer | PDF (231 KB) - Variation in KLK genes, prostate-specific antigen and risk of prostate cancer | Supplementary information

Reply to "Variation in KLK genes, prostate-specific antigen and risk of prostate cancer" - pp1035 - 1036

Rosalind Eeles, Graham Giles, David Neal, Kenneth Muir, Douglas F Easton & for the PRACTICAL Consortium

doi:10.1038/ng0908-1035

Full Text - Reply to "Variation in KLK genes, prostate-specific antigen and risk of prostate cancer" | PDF (169 KB) - Reply to "Variation in KLK genes, prostate-specific antigen and risk of prostate cancer" | Supplementary information

Victor A. McKusick 1921–2008 - p1037

David L Rimoin

doi:10.1038/ng0908-1037

Full Text - Victor A. McKusick 1921–2008 | PDF (130 KB) - Victor A. McKusick 1921–2008

High anxiety - p1038

Misha Angrist reviews Blood Matters: From Inherited Illness to Designer Babies, How the World and I Found Ourselves in the Future of the Gene by Masha Gessen

doi:10.1038/ng0908-1038

Full Text - High anxiety | PDF (137 KB) - High anxiety

Casting a wider net for diabetes susceptibility genes - pp1039 - 1040

Mark I McCarthy

doi:10.1038/ng0908-1039

Recent successes in identifying loci involved in predisposition to type 2 diabetes have been driven by genome-wide association studies in populations of European descent. A new discovery, using samples of East Asian origin, of diabetes susceptibility variants mapping to the KCNQ1 gene highlights the importance of extending these studies to a wider range of populations.

Abstract - | Full Text - Casting a wider net for diabetes susceptibility genes | PDF (183 KB) - Casting a wider net for diabetes susceptibility genes

See also: Letter by Yasuda et al. | Letter by Unoki et al.

Hedgehog in Wnterland - pp1040 - 1041

Dennis Roop & Rune Toftgård

doi:10.1038/ng0908-1040

Hedgehog signaling has a key role in hair follicle development, as well as in induction of the most common cancer in individuals of European descent, basal cell carcinoma (BCC). A new study shows that BCCs strongly resemble embryonic hair follicles and that BCC induction requires active Wnt/-catenin signaling.

Abstract - | Full Text - Hedgehog in Wnterland | PDF (754 KB) - Hedgehog in Wnterland

See also: Letter by Hoseong Yang et al.

Psychiatric genetics gets a boost - pp1042 - 1044

Brion S Maher, Brien P Riley & Kenneth S Kendler

doi:10.1038/ng0908-1042

Defining the molecular nature of the genetic risk of psychiatric disorders has been notoriously difficult. Now, a flurry of genome-wide association studies for schizophrenia and bipolar disorder provides preliminary evidence for replicated signals.

Abstract - | Full Text - Psychiatric genetics gets a boost | PDF (177 KB) - Psychiatric genetics gets a boost

See also: Brief Communication by O'Donovan et al. | Brief Communication by Ferreira et al.

Research highlights - p1045

doi:10.1038/ng0908-1045

Full Text - Research highlights | PDF (119 KB) - Research highlights

A wiki for the life sciences where authorship matters - pp1047 - 1051

Robert Hoffmann

doi:10.1038/ng.f.217

Abstract - | Full Text - A wiki for the life sciences where authorship matters | PDF (556 KB) - A wiki for the life sciences where authorship matters

Identification of loci associated with schizophrenia by genome-wide association and follow-up - pp1053 - 1055

Michael C O'Donovan, Nicholas Craddock, Nadine Norton, Hywel Williams, Timothy Peirce, Valentina Moskvina, Ivan Nikolov, Marian Hamshere, Liam Carroll, Lyudmila Georgieva, Sarah Dwyer, Peter Holmans, Jonathan L Marchini, Chris C A Spencer, Bryan Howie, Hin-Tak Leung, Annette M Hartmann, Hans-Jürgen Möller, Derek W Morris, YongYong Shi, GuoYin Feng, Per Hoffmann, Peter Propping, Catalina Vasilescu, Wolfgang Maier, Marcella Rietschel, Stanley Zammit, Johannes Schumacher, Emma M Quinn, Thomas G Schulze, Nigel M Williams, Ina Giegling, Nakao Iwata, Masashi Ikeda, Ariel Darvasi, Sagiv Shifman, Lin He, Jubao Duan, Alan R Sanders, Douglas F Levinson, Pablo V Gejman, Molecular Genetics of Schizophrenia Collaboration, Sven Cichon, Markus M Nöthen, Michael Gill, Aiden Corvin, Dan Rujescu, George Kirov & Michael J Owen

doi:10.1038/ng.201

Michael O'Donovan and colleagues present a genome-wide association study of schizophrenia in 479 cases and 2,937 controls, followed by replication in several cohorts. They report evidence for association for a susceptibility allele near ZNF804A.

Abstract - | Full Text - Identification of loci associated with schizophrenia by genome-wide association and follow-up | PDF (186 KB) - Identification of loci associated with schizophrenia by genome-wide association and follow-up | Supplementary information

See also: News and Views by Maher et al.

Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder - pp1056 - 1058

Manuel A R Ferreira, Michael C O'Donovan, Yan A Meng, Ian R Jones, Douglas M Ruderfer, Lisa Jones, Jinbo Fan, George Kirov, Roy H Perlis, Elaine K Green, Jordan W Smoller, Detelina Grozeva, Jennifer Stone, Ivan Nikolov, Kimberly Chambert, Marian L Hamshere, Vishwajit L Nimgaonkar, Valentina Moskvina, Michael E Thase, Sian Caesar, Gary S Sachs, Jennifer Franklin, Katherine Gordon-Smith, Kristin G Ardlie, Stacey B Gabriel, Christine Fraser, Brendan Blumenstiel, Matthew Defelice, Gerome Breen, Michael Gill, Derek W Morris, Amanda Elkin, Walter J Muir, Kevin A McGhee, Richard Williamson, Donald J MacIntyre, Alan W MacLean, David St Clair, Michelle Robinson, Margaret Van Beck, Ana C P Pereira, Radhika Kandaswamy, Andrew McQuillin, David A Collier, Nicholas J Bass, Allan H Young, Jacob Lawrence, I Nicol Ferrier, Adebayo Anjorin, Anne Farmer, David Curtis, Edward M Scolnick, Peter McGuffin, Mark J Daly, Aiden P Corvin, Peter A Holmans, Douglas H Blackwood, Wellcome Trust Case Control Consortium, Hugh M Gurling, Michael J Owen, Shaun M Purcell, Pamela Sklar & Nick Craddock

doi:10.1038/ng.209

Pamela Sklar and colleagues report a genome-wide association study of bipolar disorder and identify variants in the genes encoding ankyrin-3 and the alpha-1C subunit of the L-type voltage-gated calcium channel as increasing risk.

Abstract - | Full Text - Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder | PDF (314 KB) - Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder | Supplementary information

See also: News and Views by Maher et al.

Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus - pp1059 - 1061

Robert R Graham, Chris Cotsapas, Leela Davies, Rachel Hackett, Christopher J Lessard, Joanlise M Leon, Noel P Burtt, Candace Guiducci, Melissa Parkin, Casey Gates, Robert M Plenge, Timothy W Behrens, Joan E Wither, John D Rioux, Paul R Fortin, Deborah Cunninghame Graham, Andrew K Wong, Timothy J Vyse, Mark J Daly, David Altshuler, Kathy L Moser & Patrick M Gaffney

doi:10.1038/ng.200

Patrick Gaffney and colleagues report results of a genome-wide association study for systemic lupus erythematosus (SLE), identifying variants in the TNFAIP3 region on 6q23 that are strongly associated with the disease. In a related study, Lindsey Criswell and colleagues report a similar association between variants near TNFAIP3 and SLE. The same region on 6q23 has recently been associated with rheumatoid arthritis, but only a subset of risk alleles in this region seem to be common to both diseases.

Abstract - | Full Text - Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus | PDF (265 KB) - Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus | Supplementary information

Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus - pp1062 - 1064

Stacy L Musone, Kimberly E Taylor, Timothy T Lu, Joanne Nititham, Ricardo C Ferreira, Ward Ortmann, Nataliya Shifrin, Michelle A Petri, M Ilyas Kamboh, Susan Manzi, Michael F Seldin, Peter K Gregersen, Timothy W Behrens, Averil Ma, Pui-Yan Kwok & Lindsey A Criswell

doi:10.1038/ng.202

Lindsey Criswell and colleagues report an association between three independent variants near TNFAIP3 and systemic lupus erythematosus (SLE). In a related study, Patrick Gaffney and colleagues report results of a genome-wide association study for SLE, also identifying variants in the TNFAIP3 region on 6q23 that are strongly associated with the disease. The same region on 6q23 has recently been associated with rheumatoid arthritis, but only a subset of risk alleles in this region seem to be common to both diseases.

Abstract - | Full Text - Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus | PDF (235 KB) - Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus | Supplementary information

Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum - pp1065 - 1067

Juliane Najm, Denise Horn, Isabella Wimplinger, Jeffrey A Golden, Victor V Chizhikov, Jyotsna Sudi, Susan L Christian, Reinhard Ullmann, Alma Kuechler, Carola A Haas, Armin Flubacher, Lawrence R Charnas, Gökhan Uyanik, Ulrich Frank, Eva Klopocki, William B Dobyns & Kerstin Kutsche

doi:10.1038/ng.194

Kerstin Kutsche and colleagues report that mutations in CASK cause an X-linked brain malformation marked by microcephaly and hypoplasia of the brainstem and cerebellum. CASK encodes a scaffolding protein that is thought to play important roles in neuronal development and synaptic trafficking.

Abstract - | Full Text - Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum | PDF (365 KB) - Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum | Supplementary information

Detection of sharing by descent, long-range phasing and haplotype imputation - pp1068 - 1075

Augustine Kong, Gisli Masson, Michael L Frigge, Arnaldur Gylfason, Pasha Zusmanovich, Gudmar Thorleifsson, Pall I Olason, Andres Ingason, Stacy Steinberg, Thorunn Rafnar, Patrick Sulem, Magali Mouy, Frosti Jonsson, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Hreinn Stefansson & Kari Stefansson

doi:10.1038/ng.216

Augustine Kong and colleagues describe an approach for phasing SNPs into long haplotypes spanning multiple blocks of linkage disequilibrium. The method, termed long-range phasing, can be also used to impute long haplotypes for ungenotyped individuals.

Abstract - | Full Text - Detection of sharing by descent, long-range phasing and haplotype imputation | PDF (559 KB) - Detection of sharing by descent, long-range phasing and haplotype imputation | Supplementary information

Evolutionary toggling of the MAPT 17q21.31 inversion region - pp1076 - 1083

Michael C Zody, Zhaoshi Jiang, Hon-Chung Fung, Francesca Antonacci, LaDeana W Hillier, Maria Francesca Cardone, Tina A Graves, Jeffrey M Kidd, Ze Cheng, Amr Abouelleil, Lin Chen, John Wallis, Jarret Glasscock, Richard K Wilson, Amy Denise Reily, Jaime Duckworth, Mario Ventura, John Hardy, Wesley C Warren & Evan E Eichler

doi:10.1038/ng.193

Evan Eichler and colleagues present a sequence assembly of the inverted H2 haplotype of human chromosome 17q21.31 and show that the inversion is polymorphic in other great ape species. Their analyses suggest that the H2 configuration represents the ancestral state in great apes and that inversions have occurred independently in the human and chimpanzee lineages.

Abstract - | Full Text - Evolutionary toggling of the MAPT 17q21.31 inversion region | PDF (688 KB) - Evolutionary toggling of the MAPT 17q21.31 inversion region | Supplementary information

Max-independent functions of Myc in Drosophila melanogaster - pp1084 - 1091

Dominik Steiger, Michael Furrer, Daniela Schwinkendorf & Peter Gallant

doi:10.1038/ng.178

Peter Gallant and colleagues show that the control of endoreplication and cell competition in Drosophila are activities of Myc proto-oncogene in vivo that do not require the association with its Max binding partner. Further, a Myc derivative that does not interact with Max retains substantial biological activity, and Myc can control RNA polymerase III independently of Max.

Abstract - | Full Text - Max-independent functions of Myc in Drosophila melanogaster | PDF (642 KB) - Max-independent functions of Myc in Drosophila melanogaster | Supplementary information

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus - pp1092 - 1097

Kazuki Yasuda, Kazuaki Miyake, Yukio Horikawa, Kazuo Hara, Haruhiko Osawa, Hiroto Furuta, Yushi Hirota, Hiroyuki Mori, Anna Jonsson, Yoshifumi Sato, Kazuya Yamagata, Yoshinori Hinokio, He-Yao Wang, Toshihito Tanahashi, Naoto Nakamura, Yoshitomo Oka, Naoko Iwasaki, Yasuhiko Iwamoto, Yuichiro Yamada, Yutaka Seino, Hiroshi Maegawa, Atsunori Kashiwagi, Jun Takeda, Eiichi Maeda, Hyoung Doo Shin, Young Min Cho, Kyong Soo Park, Hong Kyu Lee, Maggie C Y Ng, Ronald C W Ma, Wing-Yee So, Juliana C N Chan, Valeriya Lyssenko, Tiinamaija Tuomi, Peter Nilsson, Leif Groop, Naoyuki Kamatani, Akihiro Sekine, Yusuke Nakamura, Ken Yamamoto, Teruhiko Yoshida, Katsushi Tokunaga, Mitsuo Itakura, Hideichi Makino, Kishio Nanjo, Takashi Kadowaki & Masato Kasuga

doi:10.1038/ng.207

Masato Kasuga and colleagues and Shiro Maeda and colleagues each report the independent identification of SNPs in KCNQ1 associated with type 2 diabetes in the Japanese population. Each group replicated the associations in other populations of East Asian and European descent.

First Paragraph - | Full Text - Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus | PDF (425 KB) - Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus | Supplementary information

See also: News and Views by McCarthy | Letter by Unoki et al.

SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations - pp1098 - 1102

Hiroyuki Unoki, Atsushi Takahashi, Takahisa Kawaguchi, Kazuo Hara, Momoko Horikoshi, Gitte Andersen, Daniel P K Ng, Johan Holmkvist, Knut Borch-Johnsen, Torben Jørgensen, Annelli Sandbæk, Torsten Lauritzen, Torben Hansen, Siti Nurbaya, Tatsuhiko Tsunoda, Michiaki Kubo, Tetsuya Babazono, Hiroshi Hirose, Matsuhiko Hayashi, Yasuhiko Iwamoto, Atsunori Kashiwagi, Kohei Kaku, Ryuzo Kawamori, E Shyong Tai, Oluf Pedersen, Naoyuki Kamatani, Takashi Kadowaki, Ryuichi Kikkawa, Yusuke Nakamura & Shiro Maeda

doi:10.1038/ng.208

Masato Kasuga and colleagues and Shiro Maeda and colleagues each report the independent identification of SNPs in KCNQ1 associated with type 2 diabetes in the Japanese population. Each group replicated the associations in other populations of East Asian and European descent.

First Paragraph - | Full Text - SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations | PDF (279 KB) - SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations | Supplementary information

See also: News and Views by McCarthy | Letter by Yasuda et al.

Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis - pp1103 - 1106

Sylvia Hofmann, Andre Franke, Annegret Fischer, Gunnar Jacobs, Michael Nothnagel, Karoline I Gaede, Manfred Schürmann, Joachim Müller-Quernheim, Michael Krawczak, Philip Rosenstiel & Stefan Schreiber

doi:10.1038/ng.198

Stefan Schreiber and colleagues report the results of a genome-wide association study for sarcoidosis, a complex chronic inflammatory disorder. Variants near ANXA11 and PLAC9 are associated with elevated risk of the disease, with ANXA11 as the stronger candidate.

First Paragraph - | Full Text - Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis | PDF (452 KB) - Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis | Supplementary information

Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease - pp1107 - 1112

Steven A McCarroll, Alan Huett, Petric Kuballa, Shannon D Chilewski, Aimee Landry, Philippe Goyette, Michael C Zody, Jennifer L Hall, Steven R Brant, Judy H Cho, Richard H Duerr, Mark S Silverberg, Kent D Taylor, John D Rioux, David Altshuler, Mark J Daly & Ramnik J Xavier

doi:10.1038/ng.215

Mark Daly, Ramnik Xavier and colleagues report that a 20-kb deletion polymorphism upstream of IRGM is associated with altered IRGM expression and Crohn's disease. They also show that manipulation of IRGM levels in cells modulated the efficiency of autophagic responses to internalized bacteria, suggesting a mechanism by which the deletion variant might influence disease risk.

First Paragraph - | Full Text - Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease | PDF (557 KB) - Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease | Supplementary information

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia - pp1113 - 1118

Birgit S Budde, Yasmin Namavar, Peter G Barth, Bwee Tien Poll-The, Gudrun Nürnberg, Christian Becker, Fred van Ruissen, Marian A J Weterman, Kees Fluiter, Erik T te Beek, Eleonora Aronica, Marjo S van der Knaap, Wolfgang Höhne, Mohammad Reza Toliat, Yanick J Crow, Maja Steinlin, Thomas Voit, Filip Roelens, Wim Brussel, Knut Brockmann, Marten Kyllerman, Eugen Boltshauser, Gerhard Hammersen, Michèl Willemsen, Lina Basel-Vanagaite, Ingeborg Krägeloh-Mann, Linda S de Vries, Laszlo Sztriha, Francesco Muntoni, Colin D Ferrie, Roberta Battini, Raoul C M Hennekam, Eugenio Grillo, Frits A Beemer, Loes M E Stoets, Bernd Wollnik, Peter Nürnberg & Frank Baas

doi:10.1038/ng.204

Frank Baas and colleagues report mutations in three of the four subunits of the tRNA-splicing endonuclease complex in families with two subtypes of pontocerebellar hypoplasia. The findings implicate tRNA processing in neurological disorders.

First Paragraph - | Full Text - tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia | PDF (675 KB) - tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia | Supplementary information

ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF- bioavailability regulation - pp1119 - 1123

Carine Le Goff, Fanny Morice-Picard, Nathalie Dagoneau, Lauren W Wang, Claire Perrot, Yanick J Crow, Florence Bauer, Elisabeth Flori, Catherine Prost-Squarcioni, Deborah Krakow, Gaoxiang Ge, Daniel S Greenspan, Damien Bonnet, Martine Le Merrer, Arnold Munnich, Suneel S Apte & Valérie Cormier-Daire

doi:10.1038/ng.199

Valerie Cormier-Daire and colleagues report mutations in ADAMTSL2 in geleophysic dysplasia, a connective tissue disorder. The authors present evidence that ADAMTSL2 is an extracellular matrix protein regulating the bioavailability of TGF-.

First Paragraph - | Full Text - ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF- bioavailability regulation | PDF (436 KB) - ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF- bioavailability regulation | Supplementary information

A common sequence motif associated with recombination hot spots and genome instability in humans - pp1124 - 1129

Simon Myers, Colin Freeman, Adam Auton, Peter Donnelly & Gil McVean

doi:10.1038/ng.213

Gil McVean and colleagues examine recombination hot spots in the human genome, using new search methods and drawing on HapMap II to identify an extended family of hot spot–associated motifs. They report a common sequence motif estimated to be found in 40% of recombination hot spots.

First Paragraph - | Full Text - A common sequence motif associated with recombination hot spots and genome instability in humans | PDF (448 KB) - A common sequence motif associated with recombination hot spots and genome instability in humans | Supplementary information

Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/-catenin signaling - pp1130 - 1135

Steven Hoseong Yang, Thomas Andl, Vladimir Grachtchouk, Aiqin Wang, Jianhong Liu, Li-Jyun Syu, Jenny Ferris, Timothy S Wang, Adam B Glick, Sarah E Millar & Andrzej A Dlugosz

doi:10.1038/ng.192

Andrzej Dlugosz and colleagues report that Hedgehog-dependent skin tumors require canonical Wnt signaling for their development.

First Paragraph - | Full Text - Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/-catenin signaling | PDF (855 KB) - Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/-catenin signaling | Supplementary information

See also: News and Views by Roop & Toftgård

A developmental framework for dissected leaf formation in the Arabidopsis relative Cardamine hirsuta - pp1136 - 1141

Michalis Barkoulas, Angela Hay, Evagelia Kougioumoutzi & Miltos Tsiantis

doi:10.1038/ng.189

Miltos Tsiantis and colleagues examine leaf formation in Arabidopsis thaliana, which has simple, undivided leaves, and Cardamine hirsuta, which has a subdivided leaf blade with individual leaflets. Using genetics, marker gene expression and cell lineage tracing, the authors show that lateral leaflet formation in C. hirsuta requires establishment of growth foci that form after leaf initiation.

First Paragraph - | Full Text - A developmental framework for dissected leaf formation in the Arabidopsis relative Cardamine hirsuta | PDF (734 KB) - A developmental framework for dissected leaf formation in the Arabidopsis relative Cardamine hirsuta | Supplementary information