"The identification of additional mutations in TDP-43 in other ALS patients will confirm that this gene is a prominent cause of this type of disorder"

A team of Canadian and French researchers has identified a novel gene responsible for a significant fraction of ALS cases. via EurekAlert!

"Genetic studies of this kind are revealing new and unsuspected connections between diseases"

An international collaboration of scientists from Europe and the US has identified six new genes which play a role in the development of type 2 diabetes , extending the total number of genes implicated in ... via Huliq.com

Cancer susceptibility genes do not not affect all races the same way, a study has shown for the first time. via Channel 4

TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis

Nature Genetics 40, 572 (2008). doi:10.1038/ng.132

Authors: Edor Kabashi, Paul N Valdmanis, Patrick Dion, Dan Spiegelman, Brendan J McConkey, Christine Vande Velde, Jean-Pierre Bouchard, Lucette Lacomblez, Ksenia Pochigaeva, Francois Salachas, Pierre-Francois Pradat, William Camu, Vincent Meininger, Nicolas Dupre & Guy A Rouleau

Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals—six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)—and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis.

Differential effects of oncogenic K-Ras and N-Ras on proliferation, differentiation and tumor progression in the colon

Nature Genetics 40, 600 (2008). doi:10.1038/ng.115

Authors: Kevin M Haigis, Krystle R Kendall, Yufang Wang, Ann Cheung, Marcia C Haigis, Jonathan N Glickman, Michiko Niwa-Kawakita, Alejandro Sweet-Cordero, Judith Sebolt-Leopold, Kevin M Shannon, Jeffrey Settleman, Marco Giovannini & Tyler Jacks

A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3

Nature Genetics 40, 623 (2008). doi:10.1038/ng.111

Authors: Ian PM Tomlinson, Emily Webb, Luis Carvajal-Carmona, Peter Broderick, Kimberley Howarth, Alan M Pittman, Sarah Spain, Steven Lubbe, Axel Walther, Kate Sullivan, Emma Jaeger, Sarah Fielding, Andrew Rowan, Jayaram Vijayakrishnan, Enric Domingo, Ian Chandler, Zoe Kemp, Mobshra Qureshi, Susan M Farrington, Albert Tenesa, James GD Prendergast, Rebecca A Barnetson, Steven Penegar, Ella Barclay, Wendy Wood, Lynn Martin, Maggie Gorman, Huw Thomas, Julian Peto, D Timothy Bishop, Richard Gray, Eamonn R Maher, Anneke Lucassen, David Kerr, D Gareth R Evans, Clemens Schafmayer, Stephan Buch, Henry Völzke, Jochen Hampe, Stefan Schreiber, Ulrich John, Thibaud Koessler, Paul Pharoah, Tom van Wezel, Hans Morreau, Juul T Wijnen, John L Hopper, Melissa C Southey, Graham G Giles, Gianluca Severi, Sergi Castellví-Bel, Clara Ruiz-Ponte, Angel Carracedo, Antoni Castells, Asta Försti, Kari Hemminki, Pavel Vodicka, Alessio Naccarati, Lara Lipton, Judy WC Ho, K K Cheng, Pak C Sham, J Luk, Jose AG Agúndez, Jose M Ladero, Miguel de la Hoya, Trinidad Caldés, Iina Niittymäki, Sari Tuupanen, Auli Karhu, Lauri Aaltonen, Jean-Baptiste Cazier, Harry Campbell, Malcolm G Dunlop & Richard S Houlston

To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P

Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21

Nature Genetics 40, 631 (2008). doi:10.1038/ng.133

Authors: Albert Tenesa, Susan M Farrington, James G D Prendergast, Mary E Porteous, Marion Walker, Naila Haq, Rebecca A Barnetson, Evropi Theodoratou, Roseanne Cetnarskyj, Nicola Cartwright, Colin Semple, Andrew J Clark, Fiona J L Reid, Lorna A Smith, Kostas Kavoussanakis, Thibaud Koessler, Paul D P Pharoah, Stephan Buch, Clemens Schafmayer, Jürgen Tepel, Stefan Schreiber, Henry Völzke, Carsten O Schmidt, Jochen Hampe, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Stefan Wilkening, Federico Canzian, Gabriel Capella, Victor Moreno, Ian J Deary, John M Starr, Ian P M Tomlinson, Zoe Kemp, Kimberley Howarth, Luis Carvajal-Carmona, Emily Webb, Peter Broderick, Jayaram Vijayakrishnan, Richard S Houlston, Gad Rennert, Dennis Ballinger, Laura Rozek, Stephen B Gruber, Koichi Matsuda, Tomohide Kidokoro, Yusuke Nakamura, Brent W Zanke, Celia M T Greenwood, Jagadish Rangrej, Rafal Kustra, Alexandre Montpetit, Thomas J Hudson, Steven Gallinger, Harry Campbell & Malcolm G Dunlop

In a genome-wide association study to identify loci associated with colorectal cancer (CRC) risk, we genotyped 555,510 SNPs in 1,012 early-onset Scottish CRC cases and 1,012 controls (phase 1). In phase 2, we genotyped the 15,008 highest-ranked SNPs in 2,057 Scottish cases and 2,111 controls. We then genotyped the five highest-ranked SNPs from the joint phase 1 and 2 analysis in 14,500 cases and 13,294 controls from seven populations, and identified a previously unreported association, rs3802842 on 11q23 (OR = 1.1; P = 5.8 × 10−10), showing population differences in risk. We also replicated and fine-mapped associations at 8q24 (rs7014346; OR = 1.19; P = 8.6 × 10−26) and 18q21 (rs4939827; OR = 1.2; P = 7.8 × 10−28). Risk was greater for rectal than for colon cancer for rs3802842 (P

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes

Nature Genetics 40, 638 (2008). doi:10.1038/ng.120

Authors: Eleftheria Zeggini, Laura J Scott, Richa Saxena, Benjamin F Voight, Jonathan L Marchini, Tianle Hu, Paul IW de Bakker, Gonçalo R Abecasis, Peter Almgren, Gitte Andersen, Kristin Ardlie, Kristina Bengtsson Boström, Richard N Bergman, Lori L Bonnycastle, Knut Borch-Johnsen, Noël P Burtt, Hong Chen, Peter S Chines, Mark J Daly, Parimal Deodhar, Chia-Jen Ding, Alex S F Doney, William L Duren, Katherine S Elliott, Michael R Erdos, Timothy M Frayling, Rachel M Freathy, Lauren Gianniny, Harald Grallert, Niels Grarup, Christopher J Groves, Candace Guiducci, Torben Hansen, Christian Herder, Graham A Hitman, Thomas E Hughes, Bo Isomaa, Anne U Jackson, Torben Jørgensen, Augustine Kong, Kari Kubalanza, Finny G Kuruvilla, Johanna Kuusisto, Claudia Langenberg, Hana Lango, Torsten Lauritzen, Yun Li, Cecilia M Lindgren, Valeriya Lyssenko, Amanda F Marvelle, Christa Meisinger, Kristian Midthjell, Karen L Mohlke, Mario A Morken, Andrew D Morris, Narisu Narisu, Peter Nilsson, Katharine R Owen, Colin NA Palmer, Felicity Payne, John R B Perry, Elin Pettersen, Carl Platou, Inga Prokopenko, Lu Qi, Li Qin, Nigel W Rayner, Matthew Rees, Jeffrey J Roix, Anelli Sandbæk, Beverley Shields, Marketa Sjögren, Valgerdur Steinthorsdottir, Heather M Stringham, Amy J Swift, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Nicholas J Timpson, Tiinamaija Tuomi, Jaakko Tuomilehto, Mark Walker, Richard M Watanabe, Michael N Weedon, Cristen J Willer, Thomas Illig, Kristian Hveem, Frank B Hu, Markku Laakso, Kari Stefansson, Oluf Pedersen, Nicholas J Wareham, Inês Barroso, Andrew T Hattersley, Francis S Collins, Leif Groop, Mark I McCarthy, Michael Boehnke & David Altshuler

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and ∼2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 × 10−14), CDC123-CAMK1D (P = 1.2 × 10−10), TSPAN8-LGR5 (P = 1.1 × 10−9), THADA (P = 1.1 × 10−9), ADAMTS9 (P = 1.2 × 10−8) and NOTCH2 (P = 4.1 × 10−8) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.