Systems biology unlimited - p505

doi:10.1038/ng0509-505

Sequencing technologies have unleashed more than enough quantitative data to test systems models of genome function, and sequence data are now driving a new systems biology. The new RNA entities uncovered may require new concepts of how genomes regulate their own expression.

Abstract - | Full Text - Systems biology unlimited | PDF (141 KB) - Systems biology unlimited

Endless forms most beautiful and wonderful - p507

Stephen C. Stearns reviews Ecological Developmental Biology: Integrating Epigenetics, Medicine, and Evolution by Scott F. Gilbert & David Epel

doi:10.1038/ng0509-507

Full Text - Endless forms most beautiful and wonderful | PDF (166 KB) - Endless forms most beautiful and wonderful

TMPRSS2-ERG and PTEN loss in prostate cancer - pp509 - 510

Jeremy A Squire

doi:10.1038/ng0509-509

Two studies show that the common recurrent gene fusion between TMPRSS2 and ERG promotes prostate cancer in both mouse and humans when PTEN is concurrently lost. In human prostate cancer, the presence of both these aberrations may be indicative of poor prognosis, suggesting that preclinical therapeutic research should target both of these pathways.

Abstract - | Full Text - TMPRSS2-ERG and PTEN loss in prostate cancer | PDF (537 KB) - TMPRSS2-ERG and PTEN loss in prostate cancer

See also: Brief Communication by King et al. | Letter by Carver et al.

X-cess of variants in XLMR - pp510 - 512

David L Nelson & Richard A Gibbs

doi:10.1038/ng0509-510

A new study reports large-scale systematic resequencing of the coding exons of the X chromosome in males with X-linked mental retardation (XLMR), illustrating the challenge of sorting through large amounts of benign variation in order to identify disease-causing sequence changes.

Abstract - | Full Text - X-cess of variants in XLMR | PDF (234 KB) - X-cess of variants in XLMR

See also: Article by Tarpey et al.

Of flaky tails and itchy skin - pp512 - 513

Donata Vercelli

doi:10.1038/ng0509-512

A new study defines the flaky tail mouse as a model for human atopic dermatitis caused by a null mutation in the gene encoding filaggrin, a key component of the epidermal barrier. Research in these mice will help explain how a disrupted barrier contributes to the pathogenesis of atopic dermatitis and to asthma arising in the context of atopic skin disease.

Abstract - | Full Text - Of flaky tails and itchy skin | PDF (253 KB) - Of flaky tails and itchy skin

See also: Letter by Fallon et al.

Research Highlights - p514

doi:10.1038/ng0509-514

Full Text - Research Highlights | PDF (117 KB) - Research Highlights

Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma - pp518 - 520

Lavanya H Palavalli, Todd D Prickett, John R Wunderlich, Xiaomu Wei, Allison S Burrell, Patricia Porter-Gill, Sean Davis, Chenwei Wang, Julia C Cronin, Neena S Agrawal, Jimmy C Lin, Wendy Westbroek, Shelley Hoogstraten-Miller, Alfredo A Molinolo, Patricia Fetsch, Armando C Filie, Michael P O'Connell, Carolyn E Banister, Jason D Howard, Phillip Buckhaults, Ashani T Weeraratna, Lawrence C Brody, Steven A Rosenberg & Yardena Samuels

doi:10.1038/ng.340

Yardena Samuels and colleagues report a mutational analysis of the matrix metalloproteinase gene family in cutaneous metastatic melanoma. They find frequent somatic mutations in MMP8 and present functional evidence that wild-type MMP-8 inhibits melanoma progression.

Abstract - | Full Text - Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma | PDF (356 KB) - Analysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma | Supplementary information

Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer - pp521 - 523

Gijs van Haaften, Gillian L Dalgliesh, Helen Davies, Lina Chen, Graham Bignell, Chris Greenman, Sarah Edkins, Claire Hardy, Sarah O'Meara, Jon Teague, Adam Butler, Jonathan Hinton, Calli Latimer, Jenny Andrews, Syd Barthorpe, Dave Beare, Gemma Buck, Peter J Campbell, Jennifer Cole, Simon Forbes, Mingming Jia, David Jones, Chai Yin Kok, Catherine Leroy, Meng-Lay Lin, David J McBride, Mark Maddison, Simon Maquire, Kirsten McLay, Andrew Menzies, Tatiana Mironenko, Lee Mulderrig, Laura Mudie, Erin Pleasance, Rebecca Shepherd, Raffaella Smith, Lucy Stebbings, Philip Stephens, Gurpreet Tang, Patrick S Tarpey, Rachel Turner, Kelly Turrell, Jennifer Varian, Sofie West, Sara Widaa, Paul Wray, V Peter Collins, Koichi Ichimura, Simon Law, John Wong, Siu Tsan Yuen, Suet Yi Leung, Giovanni Tonon, Ronald A DePinho, Yu-Tzu Tai, Kenneth C Anderson, Richard J Kahnoski, Aaron Massie, Sok Kean Khoo, Bin Tean Teh, Michael R Stratton & P Andrew Futreal

doi:10.1038/ng.349

Andrew Futreal and colleagues report inactivating somatic mutations in the histone lysine demethylase gene UTX in human cancers, including multiple myelomas, esophageal squamous carcinomas, renal clear cell carcinomas, acute and chronic myeloid leukemias, breast and colorectal cancers and glioblastomas, identifying UTX as a new tumor suppressor gene.

Abstract - | Full Text - Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer | PDF (221 KB) - Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer | Supplementary information

Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis - pp524 - 526

Jennifer C King, Jin Xu, John Wongvipat, Haley Hieronymus, Brett S Carver, David H Leung, Barry S Taylor, Chris Sander, Robert D Cardiff, Suzana S Couto, William L Gerald & Charles L Sawyers

doi:10.1038/ng.371

Charles Sawyers and colleagues report that mice expressing a TMPRSS2-ERG fusion develop prostatic intraepithelial neoplasia, but only in the context of PI3-kinase pathway activation mediated by either Pten loss or Akt activation. They also find that human TMPRSS2-ERG–positive tumors are enriched for PTEN loss, suggesting that these two events cooperate in human prostate tumorigenesis.

Abstract - | Full Text - Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis | PDF (385 KB) - Cooperativity of TMPRSS2-ERG with PI3-kinase pathway activation in prostate oncogenesis | Supplementary information

See also: News and Views by Squire | Letter by Carver et al.

A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits - pp527 - 534

Yoon Shin Cho, Min Jin Go, Young Jin Kim, Jee Yeon Heo, Ji Hee Oh, Hyo-Jeong Ban, Dankyu Yoon, Mi Hee Lee, Dong-Joon Kim, Miey Park, Seung-Hun Cha, Jun-Woo Kim, Bok-Ghee Han, Haesook Min, Younjhin Ahn, Man Suk Park, Hye Ree Han, Hye-Yoon Jang, Eun Young Cho, Jong-Eun Lee, Nam H Cho, Chol Shin, Taesung Park, Ji Wan Park, Jong-Keuk Lee, Lon Cardon, Geraldine Clarke, Mark I McCarthy, Jong-Young Lee, Jong-Koo Lee, Bermseok Oh & Hyung-Lae Kim

doi:10.1038/ng.357

Hyung-Lae Kim and colleagues report a genome-wide association study of quantitative traits of biomedical importance in Koreans. Although some loci were previously detected in European populations, others are new.

Abstract - | Full Text - A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits | PDF (524 KB) - A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits | Supplementary information

A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation - pp535 - 543

Patrick S Tarpey, Raffaella Smith, Erin Pleasance, Annabel Whibley, Sarah Edkins, Claire Hardy, Sarah O'Meara, Calli Latimer, Ed Dicks, Andrew Menzies, Phil Stephens, Matt Blow, Chris Greenman, Yali Xue, Chris Tyler-Smith, Deborah Thompson, Kristian Gray, Jenny Andrews, Syd Barthorpe, Gemma Buck, Jennifer Cole, Rebecca Dunmore, David Jones, Mark Maddison, Tatiana Mironenko, Rachel Turner, Kelly Turrell, Jennifer Varian, Sofie West, Sara Widaa, Paul Wray, Jon Teague, Adam Butler, Andrew Jenkinson, Mingming Jia, David Richardson, Rebecca Shepherd, Richard Wooster, M Isabel Tejada, Francisco Martinez, Gemma Carvill, Rene Goliath, Arjan P M de Brouwer, Hans van Bokhoven, Hilde Van Esch, Jamel Chelly, Martine Raynaud, Hans-Hilger Ropers, Fatima E Abidi, Anand K Srivastava, James Cox, Ying Luo, Uma Mallya, Jenny Moon, Josef Parnau, Shehla Mohammed, John L Tolmie, Cheryl Shoubridge, Mark Corbett, Alison Gardner, Eric Haan, Sinitdhorn Rujirabanjerd, Marie Shaw, Lucianne Vandeleur, Tod Fullston, Douglas F Easton, Jackie Boyle, Michael Partington, Anna Hackett, Michael Field, Cindy Skinner, Roger E Stevenson, Martin Bobrow, Gillian Turner, Charles E Schwartz, Jozef Gecz, F Lucy Raymond, P Andrew Futreal & Michael R Stratton

doi:10.1038/ng.367

Tarpey et al. carry out a large-scale systematic sequencing of the majority of X-chromosome coding exons from 208 families with multiple individuals with mental retardation and a pattern of transmission compatible with X linkage in order to identify XLMR-causative mutations. They find several mutations that appear to be causative in loci already known to be involved in XLMR, as well as new data about those loci, and make inferences about the role of the different classes of variants in these diseases.

Abstract - | Full Text - A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation | PDF (469 KB) - A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation | Supplementary information

See also: News and Views by Nelson & Gibbs

Braf^V600E cooperates with Pten loss to induce metastatic melanoma - pp544 - 552

David Dankort, David P Curley, Robert A Cartlidge, Betsy Nelson, Anthony N Karnezis, William E Damsky Jr, Mingjian J You, Ronald A DePinho, Martin McMahon & Marcus Bosenberg

doi:10.1038/ng.356

Martin McMahon and colleagues have generated a new mouse model of metastatic melanoma by generating mice with an activating mutation of Braf and deletion of Pten. The mice show metastatic melanoma with 100% penetrance and short latency, and should serve as a useful pre-clinical model in which to evaluate new therapies.

Abstract - | Full Text - BrafV600E cooperates with Pten loss to induce metastatic melanoma | PDF (1,303 KB) - BrafV600E cooperates with Pten loss to induce metastatic melanoma | Supplementary information

The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line - pp553 - 562

The FANTOM Consortium & Riken Omics Science Center

doi:10.1038/ng.375

The FANTOM4 study identified transcriptional start sites active during proliferation arrest and differentiation of the human monocytic cell line THP-1. Systematic knockdown of 52 transcription factors provide support for their model in which a complex transcriptional network regulates the differentiation process.

Abstract - | Full Text - The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line | PDF (980 KB) - The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line | Supplementary information

The regulated retrotransposon transcriptome of mammalian cells - pp563 - 571

Geoffrey J Faulkner, Yasumasa Kimura, Carsten O Daub, Shivangi Wani, Charles Plessy, Katharine M Irvine, Kate Schroder, Nicole Cloonan, Anita L Steptoe, Timo Lassmann, Kazunori Waki, Nadine Hornig, Takahiro Arakawa, Hazuki Takahashi, Jun Kawai, Alistair R R Forrest, Harukazu Suzuki, Yoshihide Hayashizaki, David A Hume, Valerio Orlando, Sean M Grimmond & Piero Carninci

doi:10.1038/ng.368

Piero Carninci and colleagues report that 6–30% of cap-selected mouse and human RNA transcripts initiate within repetitive elements. They conclude that retrotransposon transcription is far more widespread than first thought and has a major influence on the transcriptional output of mammalian genomes.

Abstract - | Full Text - The regulated retrotransposon transcriptome of mammalian cells | PDF (694 KB) - The regulated retrotransposon transcriptome of mammalian cells | Supplementary information

Tiny RNAs associated with transcription start sites in animals - pp572 - 578

Ryan J Taft, Evgeny A Glazov, Nicole Cloonan, Cas Simons, Stuart Stephen, Geoffrey J Faulkner, Timo Lassmann, Alistair R R Forrest, Sean M Grimmond, Kate Schroder, Katharine Irvine, Takahiro Arakawa, Mari Nakamura, Atsutaka Kubosaki, Kengo Hayashida, Chika Kawazu, Mitsuyoshi Murata, Hiromi Nishiyori, Shiro Fukuda, Jun Kawai, Carsten O Daub, David A Hume, Harukazu Suzuki, Valerio Orlando, Piero Carninci, Yoshihide Hayashizaki & John S Mattick

doi:10.1038/ng.312

John Mattick and Yoshihide Hayashizaki and colleagues report the identifcation of tiny RNAs approximately 18 nucleotides in length that map near transcription start sites in human, chicken and Drosophila genomes. They call them transcription initiation RNAs (tiRNAs) and show that they associate with highly expressed transcripts and sites of RNA polymerase II binding.

Abstract - | Full Text - Tiny RNAs associated with transcription start sites in animals | PDF (439 KB) - Tiny RNAs associated with transcription start sites in animals | Supplementary information

A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1) - pp579 - 584

Gilles Thomas, Kevin B Jacobs, Peter Kraft, Meredith Yeager, Sholom Wacholder, David G Cox, Susan E Hankinson, Amy Hutchinson, Zhaoming Wang, Kai Yu, Nilanjan Chatterjee, Montserrat Garcia-Closas, Jesus Gonzalez-Bosquet, Ludmila Prokunina-Olsson, Nick Orr, Walter C Willett, Graham A Colditz, Regina G Ziegler, Christine D Berg, Saundra S Buys, Catherine A McCarty, Heather Spencer Feigelson, Eugenia E Calle, Michael J Thun, Ryan Diver, Ross Prentice, Rebecca Jackson, Charles Kooperberg, Rowan Chlebowski, Jolanta Lissowska, Beata Peplonska, Louise A Brinton, Alice Sigurdson, Michele Doody, Parveen Bhatti, Bruce H Alexander, Julie Buring, I-Min Lee, Lars J Vatten, Kristian Hveem, Merethe Kumle, Richard B Hayes, Margaret Tucker, Daniela S Gerhard, Joseph F Fraumeni Jr, Robert N Hoover, Stephen J Chanock & David J Hunter

doi:10.1038/ng.353

David Hunter and colleagues report results of the CGEMS multistage genome-wide association study of breast cancer. They identify two new risk variants on chromosomes 1p11.2 and 14q24.1, and confirm several previously reported breast cancer risk loci.

First Paragraph - | Full Text - A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1) | PDF (418 KB) - A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1) | Supplementary information

Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2 - pp585 - 590

Shahana Ahmed, Gilles Thomas, Maya Ghoussaini, Catherine S Healey, Manjeet K Humphreys, Radka Platte, Jonathan Morrison, Melanie Maranian, Karen A Pooley, Robert Luben, Diana Eccles, D Gareth Evans, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Michael R Stratton, Nazneen Rahman, Kevin Jacobs, Ross Prentice, Garnet L Anderson, Aleksandar Rajkovic, J David Curb, Regina G Ziegler, Christine D Berg, Saundra S Buys, Catherine A McCarty, Heather Spencer Feigelson, Eugenia E Calle, Michael J Thun, W Ryan Diver, Stig Bojesen, Børge G Nordestgaard, Henrik Flyger, Thilo Dörk, Peter Schürmann, Peter Hillemanns, Johann H Karstens, Natalia V Bogdanova, Natalia N Antonenkova, Iosif V Zalutsky, Marina Bermisheva, Sardana Fedorova, Elza Khusnutdinova, SEARCH, Daehee Kang, Keun-Young Yoo, Dong Young Noh, Sei-Hyun Ahn, Peter Devilee, Christi J van Asperen, R A E M Tollenaar, Caroline Seynaeve, Montserrat Garcia-Closas, Jolanta Lissowska, Louise Brinton, Beata Peplonska, Heli Nevanlinna, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, John L Hopper, Melissa C Southey, Letitia Smith, Amanda B Spurdle, Marjanka K Schmidt, Annegien Broeks, Richard R van Hien, Sten Cornelissen, Roger L Milne, Gloria Ribas, Anna González-Neira, Javier Benitez, Rita K Schmutzler, Barbara Burwinkel, Claus R Bartram, Alfons Meindl, Hiltrud Brauch, Christina Justenhoven, Ute Hamann, The GENICA Consortium, Jenny Chang-Claude, Rebecca Hein, Shan Wang-Gohrke, Annika Lindblom, Sara Margolin, Arto Mannermaa, Veli-Matti Kosma, Vesa Kataja, Janet E Olson, Xianshu Wang, Zachary Fredericksen, Graham G Giles, Gianluca Severi, Laura Baglietto, Dallas R English, Susan E Hankinson, David G Cox, Peter Kraft, Lars J Vatten, Kristian Hveem, Merethe Kumle, Alice Sigurdson, Michele Doody, Parveen Bhatti, Bruce H Alexander, Maartje J Hooning, Ans M W van den Ouweland, Rogier A Oldenburg, Mieke Schutte, Per Hall, Kamila Czene, Jianjun Liu, Yuqing Li, Angela Cox, Graeme Elliott, Ian Brock, Malcolm W R Reed, Chen-Yang Shen, Jyh-Cherng Yu, Giu-Cheng Hsu, Shou-Tung Chen, Hoda Anton-Culver, Argyrios Ziogas, Irene L Andrulis, Julia A Knight, kConFab, Australian Ovarian Cancer Study Group, Jonathan Beesley, Ellen L Goode, Fergus Couch, Georgia Chenevix-Trench, Robert N Hoover, Bruce A J Ponder, David J Hunter, Paul D P Pharoah, Alison M Dunning, Stephen J Chanock & Douglas F Easton

doi:10.1038/ng.354

Douglas Easton and colleagues report results of a large multistage genome-wide association study of breast cancer. The study identifies two new breast cancer risk loci on chromosomes 3p24 and 17q23.2.

First Paragraph - | Full Text - Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2 | PDF (543 KB) - Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2 | Supplementary information

A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians - pp591 - 595

Yoichiro Kamatani, Sukanya Wattanapokayakit, Hidenori Ochi, Takahisa Kawaguchi, Atsushi Takahashi, Naoya Hosono, Michiaki Kubo, Tatsuhiko Tsunoda, Naoyuki Kamatani, Hiromitsu Kumada, Aekkachai Puseenam, Thanyachai Sura, Yataro Daigo, Kazuaki Chayama, Wasun Chantratita, Yusuke Nakamura & Koichi Matsuda

doi:10.1038/ng.348

Yusuke Nakamura and colleagues report results of a genome-wide association study for chronic hepatitis B in East Asians. They discover strong association with markers in the HLA-DP region, suggesting an important role for this locus in modulating the course of HBV infection.

First Paragraph - | Full Text - A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians | PDF (513 KB) - A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians | Supplementary information

A common variant on chromosome 11q13 is associated with atopic dermatitis - pp596 - 601

Jorge Esparza-Gordillo, Stephan Weidinger, Regina Fölster-Holst, Anja Bauerfeind, Franz Ruschendorf, Giannino Patone, Klaus Rohde, Ingo Marenholz, Florian Schulz, Tamara Kerscher, Norbert Hubner, Ulrich Wahn, Stefan Schreiber, Andre Franke, Rainer Vogler, Simon Heath, Hansjörg Baurecht, Natalija Novak, Elke Rodriguez, Thomas Illig, Min-Ae Lee-Kirsch, Andrzej Ciechanowicz, Michael Kurek, Tereza Piskackova, Milan Macek, Young-Ae Lee & Andreas Ruether

doi:10.1038/ng.347

Young-Ae Lee and colleagues report results of a genome-wide association study for atopic dermatitis. They identify a risk locus on chromosome 11q13 in a region previously associated with risk of Crohn's disease.

First Paragraph - | Full Text - A common variant on chromosome 11q13 is associated with atopic dermatitis | PDF (469 KB) - A common variant on chromosome 11q13 is associated with atopic dermatitis | Supplementary information

A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming - pp602 - 608

Padraic G Fallon, Takashi Sasaki, Aileen Sandilands, Linda E Campbell, Sean P Saunders, Niamh E Mangan, John J Callanan, Hiroshi Kawasaki, Aiko Shiohama, Akiharu Kubo, John P Sundberg, Richard B Presland, Philip Fleckman, Nobuyoshi Shimizu, Jun Kudoh, Alan D Irvine, Masayuki Amagai & W H Irwin McLean

doi:10.1038/ng.358

Irwin McLean and colleagues show that the flaky tail mouse mutant has a frameshift mutation in the gene encoding filaggrin. Topical application of allergen to flaky tail mice results in skin inflammation and enhanced cutaneous allergen priming, shedding light on the mechanisms underlying filaggrin-related atopic disease.

First Paragraph - | Full Text - A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming | PDF (652 KB) - A homozygous frameshift mutation in the mouse Flg gene facilitates enhanced percutaneous allergen priming | Supplementary information

See also: News and Views by Vercelli

Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss - pp609 - 613

Ángeles Mencía, Silvia Modamio-Høybjør, Nick Redshaw, Matías Morín, Fernando Mayo-Merino, Leticia Olavarrieta, Luis A Aguirre, Ignacio del Castillo, Karen P Steel, Tamas Dalmay, Felipe Moreno & Miguel Ángel Moreno-Pelayo

doi:10.1038/ng.355

Miguel Moreno-Pelayo and colleagues report mutations in the seed region of human miR-96 segregating with progressive hearing loss in two families. In an accompanying paper, Karen Steel and colleagues show that the mouse diminuendo mutant, which also shows progressive hearing loss, carries a similar mutation in the seed region of mouse miR-96.

First Paragraph - | Full Text - Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss | PDF (686 KB) - Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss | Supplementary information

An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice - pp614 - 618

Morag A Lewis, Elizabeth Quint, Anne M Glazier, Helmut Fuchs, Martin Hrabé De Angelis, Cordelia Langford, Stijn van Dongen, Cei Abreu-Goodger, Matias Piipari, Nick Redshaw, Tamas Dalmay, Miguel Angel Moreno-Pelayo, Anton J Enright & Karen P Steel

doi:10.1038/ng.369

Karen Steel and colleagues report that the mouse diminuendo mutant, which shows progressive hearing loss, carries a mutation in the seed region of mouse miR-96. In an accompanying paper, Miguel Moreno-Pelayo and colleagues report similar mutations in the seed region of human miR-96 segregating with progressive hearing loss in two families.

First Paragraph - | Full Text - An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice | PDF (655 KB) - An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice | Supplementary information

Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate - pp619 - 624

Brett S Carver, Jennifer Tran, Anuradha Gopalan, Zhenbang Chen, Safa Shaikh, Arkaitz Carracedo, Andrea Alimonti, Caterina Nardella, Shohreh Varmeh, Peter T Scardino, Carlos Cordon-Cardo, William Gerald & Pier Paolo Pandolfi

doi:10.1038/ng.370

Pier Paolo Pandolfi and colleagues report that prostate-specific overexpression of ERG in transgenic mice results in no overt phenotype on its own but promotes progression of intraepithelial neoplasia to adenocarcinoma in a PTEN heterozygous background. They also find that human TMPRSS2-ERG–positive tumors are enriched for PTEN loss, suggesting that these two events cooperate in human prostate tumorigenesis.

First Paragraph - | Full Text - Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate | PDF (689 KB) - Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate | Supplementary information

See also: News and Views by Squire | Brief Communication by King et al.

The rise and fall of a human recombination hot spot - pp625 - 629

Alec J Jeffreys & Rita Neumann

doi:10.1038/ng.346

Alec Jeffreys and Rita Neumann identify a polymorphic recombination hot spot that was activated by a single base change roughly 70,000 years ago and has persisted in the human population despite its systematic elimination by biased gene conversion. The work provides the first example of a highly transient recombination hot spot in the human population.

First Paragraph - | Full Text - The rise and fall of a human recombination hot spot | PDF (472 KB) - The rise and fall of a human recombination hot spot | Supplementary information

RNA polymerase V transcription guides ARGONAUTE4 to chromatin - pp630 - 634

Andrzej T Wierzbicki, Thomas S Ream, Jeremy R Haag & Craig S Pikaard

doi:10.1038/ng.365

Craig Pikaard and colleagues show that AGO4 is recruited to target loci through physical interactions with nascent RNA polymerase V transcripts. They also show that the SMC hinge-domain protein DMS3 functions in the assembly of Pol V transcription complexes.

First Paragraph - | Full Text - RNA polymerase V transcription guides ARGONAUTE4 to chromatin | PDF (1,283 KB) - RNA polymerase V transcription guides ARGONAUTE4 to chromatin