Table of contents



GINA, aGAIN p133




Open-access database of candidate associations from a genome-wide SNP scan of the Framingham Heart Study pp135 - 136

Alan Herbert, Marc E Lenburg, David Ulrich, Norman P Gerry, Karen Schlauch & Michael F Christman


On the cloning of animals from terminally differentiated cells pp136 - 137

Konrad Hochedlinger & Rudolf Jaenisch


Reply to |[ldquo]|On the cloning of animals from terminally differentiated cells|[rdquo]| pp137 - 138

Xiangzhong Yang, Tao Cheng, Li-Ying Sung, Shaorong Gao, Hongmei Shen, Hui Yu, Yifang Song, Sadie L Smith, David P Tuck, Kimiko Inoue & Sherman M Weissman



Book Review

Cipher sleuth p139

Michael A Goldman reviews Francis Crick: Discoverer of the Genetic Code by Matt Ridley



News and Views

Latexin is a newly discovered regulator of hematopoietic stem cells pp141 - 142

Gerald de Haan


Deeply hidden in the bone marrow are rare hematopoietic stem cells that produce all types of blood cells in the circulatory system. A new study shows that the latexin gene affects the size of this population of cells.

See also: Article by Liang et al.

Fanconi anemia and breast cancer susceptibility pp142 - 143

Ketan J Patel


Two new studies show that the Fanconi anemia complementation group N results from biallelic mutations in PALB2, which encodes a recently identified interaction partner of the breast cancer susceptibility protein BRCA2. A third study shows that monoallelic PALB2 mutations are associated with breast cancer susceptibility, providing yet more links between Fanconi anemia, homologous recombination repair and cancer predisposition.

See also: Brief Communication by Xia et al. | Brief Communication by Reid et al. | Brief Communication by Rahman et al.

Personalized medicine and quantitative trait transcripts pp144 - 145

Douglas M Ruden


A new study identifies 'quantitative trait transcripts' for nicotine resistance in large populations of wild strains of Drosophila melanogaster by comparing global gene expression patterns, survival time and metabolite levels in the presence or absence of nicotine. The results provide proof-of-concept for a correlation-based statistical approach that can be used in personalized medicine.

See also: Letter by Passador-Gurgel et al.

Micromanaging the response to Hedgehog pp145 - 146

Philip Ingham


Members of the Hedgehog family of secreted proteins are central to animal development, with different levels of Hedgehog signaling activity specifying distinct cellular identities. A new study shows that a microRNA is involved in this process by modulating a component of the Hedgehog signal transduction pathway.

See also: Letter by Flynt et al.

A DNA methylation|[ndash]|based switch generates bistable gene expression pp146 - 147

Matthew R Bennett & Jeff Hasty


A new study examines the agn43 epigenetic switch of Escherichia coli, providing an alternative to feedback regulation as a model for gene expression regulation. Through a combination of synthetic network construction and computational modeling, the authors show that the generated bistable gene expression involves transitions between several rarely occupied states between 'on' and 'off'.

See also: Letter by Lim & van Oudenaarden

Touching base p149


Research highlights p151



Meeting Report

Human Genome Variation 2006: emerging views on structural variation and large-scale SNP analysis pp153 - 155

Gon|[ccedil]|alo Abecasis, Paul Kwong-Hang Tam, Carlos D Bustamante, Elaine A Ostrander, Stephen W Scherer, Stephen J Chanock, Pui-Yan Kwok & Anthony J Brookes


The eighth annual Human Genome Variation Meeting was held in September 2006 in the Hong Kong Special Administrative Region, China. The meeting highlighted recent advances in characterization of genetic variation, including genome-wide association studies and structural variation.


Brief Communications

Epigenetic stem cell signature in cancer pp157 - 158

Martin Widschwendter, Heidi Fiegl, Daniel Egle, Elisabeth Mueller-Holzner, Gilbert Spizzo, Christian Marth, Daniel J Weisenberger, Mihaela Campan, Joanne Young, Ian Jacobs & Peter W Laird


Fanconi anemia is associated with a defect in the BRCA2 partner PALB2 pp159 - 161

Bing Xia, Josephine C Dorsman, Najim Ameziane, Yne de Vries, Martin A Rooimans, Qing Sheng, Gerard Pals, Abdellatif Errami, Eliane Gluckman, Julian Llera, Weidong Wang, David M Livingston, Hans Joenje & Johan P de Winter


See also: News and Views by Patel

Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer pp162 - 164

Sarah Reid, Detlev Schindler, Helmut Hanenberg, Karen Barker, Sandra Hanks, Reinhard Kalb, Kornelia Neveling, Patrick Kelly, Sheila Seal, Marcel Freund, Melanie Wurm, Sat Dev Batish, Francis P Lach, Sevgi Yetgin, Heidemarie Neitzel, Hany Ariffin, Marc Tischkowitz, Christopher G Mathew, Arleen D Auerbach & Nazneen Rahman


See also: News and Views by Patel

PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene pp165 - 167

Nazneen Rahman, Sheila Seal, Deborah Thompson, Patrick Kelly, Anthony Renwick, Anna Elliott, Sarah Reid, Katarina Spanova, Rita Barfoot, Tasnim Chagtai, Hiran Jayatilake, Lesley McGuffog, Sandra Hanks, D Gareth Evans, Diana Eccles, The Breast Cancer Susceptibility Collaboration (UK), Douglas F Easton & Michael R Stratton


See also: News and Views by Patel



The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease pp168 - 177

Ekaterina Rogaeva, Yan Meng, Joseph H Lee, Yongjun Gu, Toshitaka Kawarai, Fanggeng Zou, Taiichi Katayama, Clinton T Baldwin, Rong Cheng, Hiroshi Hasegawa, Fusheng Chen, Nobuto Shibata, Kathryn L Lunetta, Raphaelle Pardossi-Piquard, Christopher Bohm, Yosuke Wakutani, L Adrienne Cupples, Karen T Cuenco, Robert C Green, Lorenzo Pinessi, Innocenzo Rainero, Sandro Sorbi, Amalia Bruni, Ranjan Duara, Robert P Friedland, Rivka Inzelberg, Wolfgang Hampe, Hideaki Bujo, You-Qiang Song, Olav M Andersen, Thomas E Willnow, Neill Graff-Radford, Ronald C Petersen, Dennis Dickson, Sandy D Der, Paul E Fraser, Gerold Schmitt-Ulms, Steven Younkin, Richard Mayeux, Lindsay A Farrer & Peter St George-Hyslop


The quantitative trait gene latexin influences the size of the hematopoietic stem cell population in mice pp178 - 188

Ying Liang, Michael Jansen, Bruce Aronow, Hartmut Geiger & Gary Van Zant


See also: News and Views by de Haan

PTEN-deficient intestinal stem cells initiate intestinal polyposis pp189 - 198

Xi C He, Tong Yin, Justin C Grindley, Qiang Tian, Toshiro Sato, W Andy Tao, Raminarao Dirisina, Kimberly S Porter-Westpfahl, Mark Hembree, Teri Johnson, Leanne M Wiedemann, Terrence A Barrett, Leroy Hood, Hong Wu & Linheng Li


Systematic pathway analysis using high-resolution fitness profiling of combinatorial gene deletions pp199 - 206

Robert P St Onge, Ramamurthy Mani, Julia Oh, Michael Proctor, Eula Fung, Ronald W Davis, Corey Nislow, Frederick P Roth & Guri Giaever




A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 pp207 - 211

Jochen Hampe, Andre Franke, Philip Rosenstiel, Andreas Till, Markus Teuber, Klaus Huse, Mario Albrecht, Gabriele Mayr, Francisco M De La Vega, Jason Briggs, Simone G|[uuml]|nther, Natalie J Prescott, Clive M Onnie, Robert H|[auml]|sler, Bence Sipos, Ulrich R F|[ouml]|lsch, Thomas Lengauer, Matthias Platzer, Christopher G Mathew, Michael Krawczak & Stefan Schreiber


A nonsynonymous SNP in PRKCH (protein kinase C |[eta]|) increases the risk of cerebral infarction pp212 - 217

Michiaki Kubo, Jun Hata, Toshiharu Ninomiya, Koichi Matsuda, Koji Yonemoto, Toshiaki Nakano, Tomonaga Matsushita, Keiko Yamazaki, Yozo Ohnishi, Susumu Saito, Takanari Kitazono, Setsuro Ibayashi, Katsuo Sueishi, Mitsuo Iida, Yusuke Nakamura & Yutaka Kiyohara


Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution pp218 - 225

Agnar Helgason, Sn|[aelig]|bj|[ouml]|rn P|[aacute]|lsson, Gudmar Thorleifsson, Struan F A Grant, Valur Emilsson, Steinunn Gunnarsdottir, Adebowale Adeyemo, Yuanxiu Chen, Guanjie Chen, Inga Reynisdottir, Rafn Benediktsson, Anke Hinney, Torben Hansen, Gitte Andersen, Knut Borch-Johnsen, Torben Jorgensen, Helmut Sch|[auml]|fer, Mezbah Faruque, Ayo Doumatey, Jie Zhou, Robert L Wilensky, Muredach P Reilly, Daniel J Rader, Yu Bagger, Claus Christiansen, Gunnar Sigurdsson, Johannes Hebebrand, Oluf Pedersen, Unnur Thorsteinsdottir, Jeffrey R Gulcher, Augustine Kong, Charles Rotimi & K|[aacute]|ri Stef|[aacute]|nsson


Common genetic variants account for differences in gene expression among ethnic groups pp226 - 231

Richard S Spielman, Laurel A Bastone, Joshua T Burdick, Michael Morley, Warren J Ewens & Vivian G Cheung


Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer pp232 - 236

Yeshayahu Schlesinger, Ravid Straussman, Ilana Keshet, Shlomit Farkash, Merav Hecht, Joseph Zimmerman, Eran Eden, Zohar Yakhini, Etti Ben-Shushan, Benjamin E Reubinoff, Yehudit Bergman, Itamar Simon & Howard Cedar


A stem cell|[ndash]|like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing pp237 - 242

Joyce E Ohm, Kelly M McGarvey, Xiaobing Yu, Linzhao Cheng, Kornel E Schuebel, Leslie Cope, Helai P Mohammad, Wei Chen, Vincent C Daniel, Wayne Yu, David M Berman, Thomas Jenuwein, Kevin Pruitt, Saul J Sharkis, D Neil Watkins, James G Herman & Stephen B Baylin


Telomere length regulates the epigenetic status of mammalian telomeres and subtelomeres pp243 - 250

Roberta Benetti, Marta Garc|[iacute]|a-Cao & Mar|[iacute]|a A Blasco


Chromosome-wide nucleosome replacement and H3.3 incorporation during mammalian meiotic sex chromosome inactivation pp251 - 258

Godfried W van der Heijden, Alwin A H A Derijck, Eszter P|[oacute]|sfai, Maud Giele, Pawel Pelczar, Liliana Ramos, Derick G Wansink, Johan van der Vlag, Antoine H F M Peters & Peter de Boer


Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate pp259 - 263

Alex S Flynt, Nan Li, Elizabeth J Thatcher, Lilianna Solnica-Krezel & James G Patton


See also: News and Views by Ingham

Quantitative trait transcripts for nicotine resistance in Drosophila melanogaster pp264 - 268

Gisele Passador-Gurgel, Wen-Ping Hsieh, Priscilla Hunt, Nigel Deighton & Greg Gibson


See also: News and Views by Ruden



Corrigendum: Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome p276

Marco Tartaglia, Len A Pennacchio, Chen Zhao, Kamlesh K Yadav, Valentina Fodale, Anna Sarkozy, Bhaswati Pandit, Kimihiko Oishi, Simone Martinelli, Wendy Schackwitz, Anna Ustaszewska, Joel Martin, James Bristow, Claudio Carta, Francesca Lepri, Cinzia Neri, Isabella Vasta, Kate Gibson, Cynthia J Curry, Juan Pedro L|[oacute]|pez Siguero, Maria Cristina Digilio, Giuseppe Zampino, Bruno Dallapiccola, Dafna Bar-Sagi & Bruce D Gelb


Corrigendum: A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva p276

Eileen M Shore, Meiqi Xu, George J Feldman, David A Fenstermacher, The FOP International Research Consortium, Matthew A Brown & Frederick S Kaplan


Corrigendum: Lamin B1 duplications cause autosomal dominant leukodystrophy p276

Quasar S Padiath, Kazumasa Saigoh, Raphael Schiffmann, Hideaki Asahara, Takeshi Yamada, Anulf Koeppen, Kirk Hogan, Louis J Pt|[aacute]||[ccaron]|ek & Ying-Hui Fu



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