September 2012

The lungs are the most common site of breast cancer metastasis. Metastatic efficiency is dictated by a complex interplay of tumor-intrinsic and host-derived factors. Allelic variability in the germline can be a major determinant of these factors, signifying that a heritable component contributes to an individual's propensity to develop metastatic disease. In this issue, Faraji et al. identify Cadm1 expression as a heritable metastasis susceptibility factor and show that tumor-intrinsic Cadm1 expression interacts with tumor-extrinsic T-cell–mediated immunity to modulate the efficiency of tumor cell metastasis to the lungs.

Image Credit: Farhoud Faraji and Thomas Geiger.

Perspectives

Heterozygous Mutations in DNA Repair Genes and Hereditary Breast Cancer: A Question of Power

Nathan A. Ellis, Kenneth Offit

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1003008

The Long Path from QTL to Gene

Norman R. Drinkwater, Michael N. Gould

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002975

GWAS of Diabetic Nephropathy: Is the GENIE out of the Bottle?

Carsten A. Böger, John R. Sedor

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002989

The Conflict within and the Escalating War between the Sex Chromosomes

Jeffrey M. Good

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002955

Research Articles

Exome Sequencing Identifies Rare Deleterious Mutations in DNA Repair Genes FANCC and BLM as Potential Breast Cancer Susceptibility Alleles

Ella R. Thompson, Maria A. Doyle, Georgina L. Ryland, Simone M. Rowley, David Y. H. Choong, Richard W. Tothill, Heather Thorne, kConFab, Daniel R. Barnes, Jason Li, Jason Ellul, Gayle K. Philip, Yoland C. Antill, Paul A. James, Alison H. Trainer, Gillian Mitchell, Ian G. Campbell

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002894

Role of Transposon-Derived Small RNAs in the Interplay between Genomes and Parasitic DNA in Rice

Misuzu Nosaka, Jun-Ichi Itoh, Yasuo Nagato, Akemi Ono, Aiko Ishiwata, Yutaka Sato

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002953

Determinants of Human Adipose Tissue Gene Expression: Impact of Diet, Sex, Metabolic Status, and Cis Genetic Regulation

Nathalie Viguerie, Emilie Montastier, Jean-José Maoret, Balbine Roussel, Marion Combes, Carine Valle, Nathalie Villa-Vialaneix, Jason S. Iacovoni, J. Alfredo Martinez, Claus Holst, Arne Astrup, Hubert Vidal, Karine Clément, Jorg Hager, Wim H. M. Saris, Dominique Langin

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002959

A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals

Frank W. Albert, Mehmet Somel, Miguel Carneiro, Ayinuer Aximu-Petri, Michel Halbwax, Olaf Thalmann, Jose A. Blanco-Aguiar, Irina Z. Plyusnina, Lyudmila Trut, Rafael Villafuerte, Nuno Ferrand, Sylvia Kaiser, Per Jensen, Svante Pääbo

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002962

UTX and UTY Demonstrate Histone Demethylase-Independent Function in Mouse Embryonic Development

Karl B. Shpargel, Toru Sengoku, Shigeyuki Yokoyama, Terry Magnuson

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002964

Tethering of the Conserved piggyBac Transposase Fusion Protein CSB-PGBD3 to Chromosomal AP-1 Proteins Regulates Expression of Nearby Genes in Humans

Lucas T. Gray, Kimberly K. Fong, Thomas Pavelitz, Alan M. Weiner

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002972

SWI/SNF-Like Chromatin Remodeling Factor Fun30 Supports Point Centromere Function in S. cerevisiae

Mickaël Durand-Dubief, William Ryan Will, Edoardo Petrini, Delphine Theodorou, Rachael R. Harris, Margaret R. Crawford, Konrad Paszkiewicz, Felix Krueger, Rosa Maria Correra, Anna T. Vetter, J. Ross Miller, Nicholas A. Kent, Patrick Varga-Weisz

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002974

The p38/MK2-Driven Exchange between Tristetraprolin and HuR Regulates AU–Rich Element–Dependent Translation

Christopher Tiedje, Natalia Ronkina, Mohammad Tehrani, Sonam Dhamija, Kathrin Laass, Helmut Holtmann, Alexey Kotlyarov, Matthias Gaestel

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002977

Complex Chromosomal Rearrangements Mediated by Break-Induced Replication Involve Structure-Selective Endonucleases

Benjamin Pardo, Andrés Aguilera

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002979

Proteome-Wide Analysis of Disease-Associated SNPs That Show Allele-Specific Transcription Factor Binding

Falk Butter, Lucy Davison, Tar Viturawong, Marion Scheibe, Michiel Vermeulen, John A. Todd, Matthias Mann

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002982

The Non-Flagellar Type III Secretion System Evolved from the Bacterial Flagellum and Diversified into Host-Cell Adapted Systems

Sophie S. Abby, Eduardo P. C. Rocha

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002983

TCF7L2 Modulates Glucose Homeostasis by Regulating CREB- and FoxO1-Dependent Transcriptional Pathway in the Liver

Kyoung-Jin Oh, Jinyoung Park, Su Sung Kim, Hyunhee Oh, Cheol Soo Choi, Seung-Hoi Koo

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002986

A Mimicking-of-DNA-Methylation-Patterns Pipeline for Overcoming the Restriction Barrier of Bacteria

Guoqiang Zhang, Wenzhao Wang, Aihua Deng, Zhaopeng Sun, Yun Zhang, Yong Liang, Yongsheng Che, Tingyi Wen

PLOS Genetics: published September 27, 2012 | https://doi.org/10.1371/journal.pgen.1002987

New Susceptibility Loci Associated with Kidney Disease in Type 1 Diabetes

Niina Sandholm, Rany M. Salem, Amy Jayne McKnight, Eoin P. Brennan, Carol Forsblom, Tamara Isakova, Gareth J. McKay, Winfred W. Williams, Denise M. Sadlier, Ville-Petteri Mäkinen, Elizabeth J. Swan, Cameron Palmer, Andrew P. Boright, Emma Ahlqvist, Harshal A. Deshmukh, Benjamin J. Keller, Huateng Huang, Aila J. Ahola, Emma Fagerholm, Daniel Gordin, Valma Harjutsalo, Bing He, Outi Heikkilä, Kustaa Hietala, Janne Kytö, Päivi Lahermo, Markku Lehto, Raija Lithovius, Anne-May Österholm, Maija Parkkonen, Janne Pitkäniemi, Milla Rosengård-Bärlund, Markku Saraheimo, Cinzia Sarti, Jenny Söderlund, Aino Soro-Paavonen, Anna Syreeni, Lena M. Thorn, Heikki Tikkanen, Nina Tolonen, Karl Tryggvason, Jaakko Tuomilehto, Johan Wadén, Geoffrey V. Gill, Sarah Prior, Candace Guiducci, Daniel B. Mirel, Andrew Taylor, S. Mohsen Hosseini, DCCT/EDIC Research Group, Hans-Henrik Parving, Peter Rossing, Lise Tarnow, Claes Ladenvall, François Alhenc-Gelas, Pierre Lefebvre, Vincent Rigalleau, Ronan Roussel, David-Alexandre Tregouet, Anna Maestroni, Silvia Maestroni, Henrik Falhammar, Tianwei Gu, Anna Möllsten, Danut Cimponeriu, Mihai Ioana, Maria Mota, Eugen Mota, Cristian Serafinceanu, Monica Stavarachi, Robert L. Hanson, Robert G. Nelson, Matthias Kretzler, Helen M. Colhoun, Nicolae Mircea Panduru, Harvest F. Gu, Kerstin Brismar, Gianpaolo Zerbini, Samy Hadjadj, Michel Marre, Leif Groop, Maria Lajer, Shelley B. Bull, Daryl Waggott, Andrew D. Paterson, David A. Savage, Stephen C. Bain, Finian Martin, Joel N. Hirschhorn, Catherine Godson, Jose C. Florez, Per-Henrik Groop, Alexander P. Maxwell

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002921

Vsx2 Controls Eye Organogenesis and Retinal Progenitor Identity Via Homeodomain and Non-Homeodomain Residues Required for High Affinity DNA Binding

Changjiang Zou, Edward M. Levine

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002924

Cadm1 Is a Metastasis Susceptibility Gene That Suppresses Metastasis by Modifying Tumor Interaction with the Cell-Mediated Immunity

Farhoud Faraji, Yanli Pang, Renard C. Walker, Rosan Nieves Borges, Li Yang, Kent W. Hunter

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002926

An Essential Role of Variant Histone H3.3 for Ectomesenchyme Potential of the Cranial Neural Crest

Samuel G. Cox, Hyunjung Kim, Aaron Timothy Garnett, Daniel Meulemans Medeiros, Woojin An, J. Gage Crump

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002938

Characterization of Inducible Models of Tay-Sachs and Related Disease

Timothy J. Sargeant, Deborah J. Drage, Susan Wang, Apostolos A. Apostolakis, Timothy M. Cox, M. Begoña Cachón-González

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002943

Co-Evolution of Mitochondrial tRNA Import and Codon Usage Determines Translational Efficiency in the Green Alga Chlamydomonas

Thalia Salinas, Francéline Duby, Véronique Larosa, Nadine Coosemans, Nathalie Bonnefoy, Patrick Motte, Laurence Maréchal-Drouard, Claire Remacle

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002946

The NDR Kinase Scaffold HYM1/MO25 Is Essential for MAK2 MAP Kinase Signaling in Neurospora crassa

Anne Dettmann, Julia Illgen, Sabine März, Timo Schürg, Andre Fleissner, Stephan Seiler

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002950

Two Distinct Repressive Mechanisms for Histone 3 Lysine 4 Methylation through Promoting 3′-End Antisense Transcription

Thanasis Margaritis, Vincent Oreal, Nathalie Brabers, Laetitia Maestroni, Adeline Vitaliano-Prunier, Joris J. Benschop, Sander van Hooff, Dik van Leenen, Catherine Dargemont, Vincent Géli, Frank C. P. Holstege

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002952

Enrichment of HP1a on Drosophila Chromosome 4 Genes Creates an Alternate Chromatin Structure Critical for Regulation in this Heterochromatic Domain

Nicole C. Riddle, Youngsook L. Jung, Tingting Gu, Artyom A. Alekseyenko, Dalal Asker, Hongxing Gui, Peter V. Kharchenko, Aki Minoda, Annette Plachetka, Yuri B. Schwartz, Michael Y. Tolstorukov, Mitzi I. Kuroda, Vincenzo Pirrotta, Gary H. Karpen, Peter J. Park, Sarah C. R. Elgin

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002954

The Kcnq1ot1 Long Non-Coding RNA Affects Chromatin Conformation and Expression of Kcnq1, but Does Not Regulate Its Imprinting in the Developing Heart

Lisa Korostowski, Natalie Sedlak, Nora Engel

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002956

Tetraspanin Is Required for Generation of Reactive Oxygen Species by the Dual Oxidase System in Caenorhabditis elegans

Hiroki Moribe, Ryouji Konakawa, Daisuke Koga, Tatsuo Ushiki, Kuniaki Nakamura, Eisuke Mekada

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002957

Genetic Modifiers of Chromatin Acetylation Antagonize the Reprogramming of Epi-Polymorphisms

Anne-Laure Abraham, Muniyandi Nagarajan, Jean-Baptiste Veyrieras, Hélène Bottin, Lars M. Steinmetz, Gaël Yvert

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002958

Rif2 Promotes a Telomere Fold-Back Structure through Rpd3L Recruitment in Budding Yeast

Heiko Poschke, Martina Dees, Michael Chang, Sandeep Amberkar, Lars Kaderali, Rodney Rothstein, Brian Luke

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002960

Coevolution within and between Regulatory Loci Can Preserve Promoter Function Despite Evolutionary Rate Acceleration

Antoine Barrière, Kacy L. Gordon, Ilya Ruvinsky

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002961

De Novo CNV Formation in Mouse Embryonic Stem Cells Occurs in the Absence of Xrcc4-Dependent Nonhomologous End Joining

Martin F. Arlt, Sountharia Rajendran, Shanda R. Birkeland, Thomas E. Wilson, Thomas W. Glover

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002981

Factors That Promote H3 Chromatin Integrity during Transcription Prevent Promiscuous Deposition of CENP-A^Cnp1 in Fission Yeast

Eun Shik Choi, Annelie Strålfors, Sandra Catania, Araceli G. Castillo, J. Peter Svensson, Alison L. Pidoux, Karl Ekwall, Robin C. Allshire

PLOS Genetics: published September 20, 2012 | https://doi.org/10.1371/journal.pgen.1002985

Variation in Genes Related to Cochlear Biology Is Strongly Associated with Adult-Onset Deafness in Border Collies

Jennifer S. Yokoyama, Ernest T. Lam, Alison L. Ruhe, Carolyn A. Erdman, Kathryn R. Robertson, Aubrey A. Webb, D. Colette Williams, Melanie L. Chang, Marjo K. Hytönen, Hannes Lohi, Steven P. Hamilton, Mark W. Neff

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002898

A Genetic Basis for a Postmeiotic X Versus Y Chromosome Intragenomic Conflict in the Mouse

Julie Cocquet, Peter J. I. Ellis, Shantha K. Mahadevaiah, Nabeel A. Affara, Daniel Vaiman, Paul S. Burgoyne

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002900

Genome-Wide Association Study for Serum Complement C3 and C4 Levels in Healthy Chinese Subjects

Xiaobo Yang, Jielin Sun, Yong Gao, Aihua Tan, Haiying Zhang, Yanling Hu, Junjie Feng, Xue Qin, Sha Tao, Zhuo Chen, Seong-Tae Kim, Tao Peng, Ming Liao, Xiaoling Lin, Zengfeng Zhang, Minzhong Tang, Li Li, Linjian Mo, Zhengjia Liang, Deyi Shi, Zhang Huang, Xianghua Huang, Ming Liu, Qian Liu, Shijun Zhang, Jeffrey M. Trent, S. Lilly Zheng, Jianfeng Xu, Zengnan Mo

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002916

Genomics of Adaptation during Experimental Evolution of the Opportunistic Pathogen Pseudomonas aeruginosa

Alex Wong, Nicolas Rodrigue, Rees Kassen

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002928

Convergence of the Transcriptional Responses to Heat Shock and Singlet Oxygen Stresses

Yann S. Dufour, Saheed Imam, Byoung-Mo Koo, Heather A. Green, Timothy J. Donohue

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002929

A Genome-Wide Association Study Identifies Five Loci Influencing Facial Morphology in Europeans

Fan Liu, Fedde van der Lijn, Claudia Schurmann, Gu Zhu, M. Mallar Chakravarty, Pirro G. Hysi, Andreas Wollstein, Oscar Lao, Marleen de Bruijne, M. Arfan Ikram, Aad van der Lugt, Fernando Rivadeneira, André G. Uitterlinden, Albert Hofman, Wiro J. Niessen, Georg Homuth, Greig de Zubicaray, Katie L. McMahon, Paul M. Thompson, Amro Daboul, Ralf Puls, Katrin Hegenscheid, Liisa Bevan, Zdenka Pausova, Sarah E. Medland, Grant W. Montgomery, Margaret J. Wright, Carol Wicking, Stefan Boehringer, Timothy D. Spector, Tomáš Paus, Nicholas G. Martin, Reiner Biffar, Manfred Kayser

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002932

H4K20me1 Contributes to Downregulation of X-Linked Genes for C. elegans Dosage Compensation

Anne Vielle, Jackie Lang, Yan Dong, Sevinc Ercan, Chitra Kotwaliwale, Andreas Rechtsteiner, Alex Appert, Q. Brent Chen, Andrea Dose, Thea Egelhofer, Hiroshi Kimura, Przemyslaw Stempor, Abby Dernburg, Jason D. Lieb, Susan Strome, Julie Ahringer

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002933

Citrullination of Histone H3 Interferes with HP1-Mediated Transcriptional Repression

Priyanka Sharma, Saliha Azebi, Patrick England, Tove Christensen, Anné Møller-Larsen, Thor Petersen, Eric Batsché, Christian Muchardt

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002934

Transcriptional Repression of Hox Genes by C. elegans HP1/HPL and H1/HIS-24

Maja Studencka, Radosław Wesołowski, Lennart Opitz, Gabriela Salinas-Riester, Jacek R. Wisniewski, Monika Jedrusik-Bode

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002940

Hominoid-Specific De Novo Protein-Coding Genes Originating from Long Non-Coding RNAs

Chen Xie, Yong E. Zhang, Jia-Yu Chen, Chu-Jun Liu, Wei-Zhen Zhou, Ying Li, Mao Zhang, Rongli Zhang, Liping Wei, Chuan-Yun Li

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002942

C. elegans SIRT6/7 Homolog SIR-2.4 Promotes DAF-16 Relocalization and Function during Stress

Wei-Chung Chiang, Daniel X. Tishkoff, Bo Yang, Joshua Wilson-Grady, Xiaokun Yu, Travis Mazer, Mark Eckersdorff, Steven P. Gygi, David B. Lombard, Ao-Lin Hsu

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002948

Functional Variants in NFKBIE and RTKN2 Involved in Activation of the NF-κB Pathway Are Associated with Rheumatoid Arthritis in Japanese

Keiko Myouzen, Yuta Kochi, Yukinori Okada, Chikashi Terao, Akari Suzuki, Katsunori Ikari, Tatsuhiko Tsunoda, Atsushi Takahashi, Michiaki Kubo, Atsuo Taniguchi, Fumihiko Matsuda, Koichiro Ohmura, Shigeki Momohara, Tsuneyo Mimori, Hisashi Yamanaka, Naoyuki Kamatani, Ryo Yamada, Yusuke Nakamura, Kazuhiko Yamamoto

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002949

A Response Regulator Interfaces between the Frz Chemosensory System and the MglA/MglB GTPase/GAP Module to Regulate Polarity in Myxococcus xanthus

Daniela Keilberg, Kristin Wuichet, Florian Drescher, Lotte Søgaard-Andersen

PLOS Genetics: published September 13, 2012 | https://doi.org/10.1371/journal.pgen.1002951

Integrative Genomic Analysis Identifies Isoleucine and CodY as Regulators of Listeria monocytogenes Virulence

Lior Lobel, Nadejda Sigal, Ilya Borovok, Eytan Ruppin, Anat A. Herskovits

PLOS Genetics: published September 6, 2012 | https://doi.org/10.1371/journal.pgen.1002887

Rare Copy Number Variants Contribute to Congenital Left-Sided Heart Disease

Marc-Phillip Hitz, Louis-Philippe Lemieux-Perreault, Christian Marshall, Yassamin Feroz-Zada, Robbie Davies, Shi Wei Yang, Anath Christopher Lionel, Guylaine D'Amours, Emmanuelle Lemyre, Rebecca Cullum, Jean-Luc Bigras, Maryse Thibeault, Philippe Chetaille, Alexandre Montpetit, Paul Khairy, Bert Overduin, Sabine Klaassen, Pamela Hoodless, Mona Nemer, Alexandre F. R. Stewart, Cornelius Boerkoel, Stephen W. Scherer, Andrea Richter, Marie-Pierre Dubé, Gregor Andelfinger

PLOS Genetics: published September 6, 2012 | https://doi.org/10.1371/journal.pgen.1002903

Normal DNA Methylation Dynamics in DICER1-Deficient Mouse Embryonic Stem Cells

Jonathan Ip, Paul Canham, K. H. Andy Choo, Yoshimi Inaba, Shelley A. Jacobs, Paul Kalitsis, Deidre M. Mattiske, Jane Ng, Richard Saffery, Nicholas C. Wong, Lee H. Wong, Jeffrey R. Mann

PLOS Genetics: published September 6, 2012 | https://doi.org/10.1371/journal.pgen.1002919

Genome-Wide Association Studies Identify Heavy Metal ATPase3 as the Primary Determinant of Natural Variation in Leaf Cadmium in Arabidopsis thaliana

Dai-Yin Chao, Adriano Silva, Ivan Baxter, Yu S. Huang, Magnus Nordborg, John Danku, Brett Lahner, Elena Yakubova, David E. Salt

PLOS Genetics: published September 6, 2012 | https://doi.org/10.1371/journal.pgen.1002923

A Gene Family Derived from Transposable Elements during Early Angiosperm Evolution Has Reproductive Fitness Benefits in Arabidopsis thaliana

Zoé Joly-Lopez, Ewa Forczek, Douglas R. Hoen, Nikoleta Juretic, Thomas E. Bureau

PLOS Genetics: published September 6, 2012 | https://doi.org/10.1371/journal.pgen.1002931

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Diversity in lung metastasis.

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