Press releases
Please quote Nature Genetics as the source of these items.
The March 2008 issue of Nature Genetics is available online.
March 2008
Natural selection shapes modern human populations
Natural selection has influenced the morphological and disease-related diversity of modern human populations, according to a study published online this week in Nature Genetics. The paper suggests that newly identified variants exhibiting reduced differentiation across populations might become medically relevant.
Several recent genome-wide studies have established that many regions of the human genome are under selection, but the degree to which this selective pressure has shaped the differences between modern human populations has been unclear.
Lluís Quintana-Murci and colleagues analyzed more than 2.8 million single-nucleotide polymorphisms (SNPs) from the second phase of the HapMap project. They show that positive selection has promoted the regional adaptation of human populations by increasing population differentiation in particular gene regions. Genes showing the strongest signature of positive selection are involved in skin pigmentation and hair development, immune response to pathogens, sensory functions such as olfaction and eye development, and insulin regulation. They also show that negative selection has reduced the degree of population differentiation in genetic variants that are associated with disease.
Natural selection has driven population differentiation in modern humans
Luis B Barreiro, Guillaume Laval, Hélène Quach, Etienne Patin & Lluís Quintana-Murci
Published online: 03 February 2008 | doi 10.1038/ng.78
Genome-wide view of prostate cancer risk
At least ten newly identified genetic variants are associated with increased susceptibility to prostate cancer, according to three studies to be published online this week in Nature Genetics. These findings double the number of variants known to be associated with risk of prostate cancer, and, in the future, may allow predictions of high risk in particular individuals.
The three groups independently carried out genome-wide association studies of thousands of individuals with or without prostate cancer. Rosalind Eeles and colleagues identified seven loci that were significantly associated with the disease on chromosomes 3, 6, 7, 10, 11, 19 and X. Stephen Chanock and colleagues report risk loci on chromosomes 7, 10 (two loci) and 11, as well as nine other loci showing suggestive association. Julius Gudmundsson's team reports risk loci on chromosomes 2 and X. Each group's findings were replicated in an independent population, and each confirmed previous susceptibility loci on chromosomes 8 and 17.
Although the specific genes that are affected by these variants have not yet been pinpointed, the authors of the studies note a few candidates. One of the risk variants on chromosome 10 is just upstream of MSMB, which encodes a protein that is produced in the prostate, and loss of MSMB expression is associated with recurrence of disease after prostatectomy. The variant on chromosome 19 is near KLK3, which encodes PSA, an enzyme that liquefies semen and is used as a standard serum marker for screening and disease monitoring.
Multiple newly identified loci associated with prostate cancer susceptibility
Rosalind A Eeles, Zsofia Kote-Jarai, Graham G Giles, Ali Amin Al Olama, Michelle Guy, Sarah K Jugurnauth, Shani Mulholland, Daniel A Leongamornlert, Stephen M Edwards, Jonathan Morrison, Helen I Field, Melissa C Southey, Gianluca Severi, Jenny L Donovan, Freddie C Hamdy, David P Dearnaley, Kenneth R Muir, Charmaine Smith, Melisa Bagnato, Audrey T Ardern-Jones, Amanda L Hall, Lynne T O'Brien, Beatrice N Gehr-Swain, Rosemary A Wilkinson, Angie Cox, Sarah Lewis, Paul M Brown, Sameer G Jhavar, Malgorzata Tymrakiewicz, Artitaya Lophatananon, Sarah L Bryant, The UK Genetic Prostate Cancer Study Collaborators, British Association of Urological Surgeons' Section of Oncology, The UK ProtecT Study Collaborators, Alan Horwich, Robert A Huddart, Vincent S Khoo, Christopher C Parker, Christopher J Woodhouse, Alan Thompson, Tim Christmas, Chris Ogden, Cyril Fisher, Charles Jamieson, Colin S Cooper, Dallas R English, John L Hopper, David E Neal & Douglas F Easton
Published online: 10 February 2008 | doi 10.1038/ng.90
Multiple loci identified in a genome-wide association study of prostate cancer
Gilles Thomas, Kevin B Jacobs, Meredith Yeager, Peter Kraft, Sholom Wacholder, Nick Orr, Kai Yu, Nilanjan Chatterjee, Robert Welch, Amy Hutchinson, Andrew Crenshaw, Geraldine Cancel-Tassin, Brian J Staats, Zhaoming Wang, Jesus Gonzalez-Bosquet, Jun Fang, Xiang Deng, Sonja I Berndt, Eugenia E Calle, Heather Spencer Feigelson, Michael J Thun, Carmen Rodriguez, Demetrius Albanes, Jarmo Virtamo, Stephanie Weinstein, Fredrick R Schumacher, Edward Giovannucci, Walter C Willett, Olivier Cussenot, Antoine Valeri, Gerald L Andriole, E David Crawford, Margaret Tucker, Daniela S Gerhard, Joseph F Fraumeni Jr, Robert Hoover, Richard B Hayes, David J Hunter & Stephen J Chanock
Published online: 10 February 2008 | doi 10.1038/ng.91
Common sequence variants on 2p15 and Xp11.22 confer susceptibility to prostate cancer
Julius Gudmundsson, Patrick Sulem, Thorunn Rafnar, Jon T Bergthorsson, Andrei Manolescu, Daniel Gudbjartsson, Bjarni A Agnarsson, Asgeir Sigurdsson, Kristrun R Benediktsdottir, Thorarinn Blondal, Margret Jakobsdottir, Simon N Stacey, Jelena Kostic, Kari T Kristinsson, Birgitta Birgisdottir, Shyamali Ghosh, Droplaug N Magnusdottir, Steinunn Thorlacius, Gudmar Thorleifsson, S Lilly Zheng, Jielin Sun, Bao-Li Chang, J Bradford Elmore, Joan P Breyer, Kate M McReynolds, Kevin M Bradley, Brian L Yaspan, Fredrik Wiklund, Par Stattin, Sara Lindström, Hans-Olov Adami, Shannon K McDonnell, Daniel J Schaid, Julie M Cunningham, Liang Wang, James R Cerhan, Jennifer L St Sauver, Sara D Isaacs, Kathleen E Wiley, Alan W Partin, Patrick C Walsh, Sonia Polo, Manuel Ruiz-Echarri, Sebastian Navarrete, Fernando Fuertes, Berta Saez, Javier Godino, Philip C Weijerman, Dorine W Swinkels, Katja K Aben, J Alfred Witjes, Brian K Suarez, Brian T Helfand, Michael L Frigge, Kristleifur Kristjansson, Carole Ober, Eirikur Jonsson, Gudmundur V Einarsson, Jianfeng Xu, Henrik Gronberg, Jeffrey R Smith, Stephen N Thibodeau, William B Isaacs, William J Catalona, Jose I Mayordomo, Lambertus A Kiemeney, Rosa B Barkardottir, Jeffrey R Gulcher, Unnur Thorsteinsdottir, Augustine Kong & Kari Stefansson
Published online: 20 January 2008 | doi 10.1038/ng.89
New syndrome of mental retardation and epilepsy identified
A new syndrome characterized by mental retardation, epilepsy, and facial and digital abnormalities is associated with a small deletion on chromosome 15, according to a study published online this week in Nature Genetics. This microdeletion accounts for 1 in 330 cases of mental retardation, and is present in 1 in 40,000 individuals in the general population.
Evan Eichler and colleagues used a high-resolution method to scan the genomes of 757 individuals with mental retardation and other anomalies, in search of chromosomal deletions and duplications. They identified an identical 1.5 million base pair deletion on chromosome 15, spanning 6 genes, in 2 unrelated individuals. The same microdeletion was later found in an additional seven individuals. One of the six deleted genes is CHRNA7, which encodes a synaptic ion channel protein that mediates neuronal signaling, and has been suggested previously to be a susceptibility factor for certain forms of epilepsy.
The authors suggest that the increasing use of high-resolution methods to identify 'submicroscopic' deletions will lead to the identification of additional syndromes with a common genetic origin.
A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures
Andrew J Sharp, Heather C Mefford, Kelly Li, Carl Baker, Cindy Skinner, Roger E Stevenson, Richard J Schroer, Francesca Novara, Manuela De Gregori, Roberto Ciccone, Adam Broomer, Iris Casuga, Yu Wang, Chunlin Xiao, Catalin Barbacioru, Giorgio Gimelli, Bernardo Dalla Bernardina, Claudia Torniero, Roberto Giorda, Regina Regan, Victoria Murday, Sahar Mansour, Marco Fichera, Lucia Castiglia, Pinella Failla, Mario Ventura, Zhaoshi Jiang, Gregory M Cooper, Samantha J L Knight, Corrado Romano, Orsetta Zuffardi, Caifu Chen, Charles E Schwartz & Evan E Eichler
Published online: 17 February 2007 | doi 10.1038/ng.2007.93
Gene hunters strike oil
A genetic variant controlling oil content in maize seeds has been identified, according to a study to be published online this week in Nature Genetics. This finding could have implications for the production and use of biofuels.
Bo Shen and colleagues mapped the variants that associate with high oil content in the 'Illinois high-oil' maize line and found that an amino acid insertion in an enzyme called DGAT has a critical role in increasing oil concentration. A survey of 71 maize lines showed that all of the lines with high concentrations of seed oil had the insertion in DGAT, while all of the lines with normal concentrations of oil did not. The authors suggest that it should now be possible to select for high-oil concentration directly by genotyping DGAT, without also selecting for other agronomic traits, as would occur when using traditional methods. Finally, they propose that the engineering of DGAT in other crops may also promote the production of seed oil.
A phenylalanine in DGAT is a key determinant of oil content and composition in maize
Peizhong Zheng, William B Allen, Keith Roesler, Mark E Williams, Shirong Zhang, Jiming Li, Kimberly Glassman, Jerry Ranch, Douglas Nubel, William Solawetz, Dinakar Bhattramakki, Victor Llaca, Stéphane Deschamps, Gan-Yuan Zhong, Mitchell C Tarczynski & Bo Shen
Published online: 17 February 2008 | doi 10.1038/ng.85
Pathway influences human hair growth and texture
Researchers have identified the genetic basis of two related but clinically distinct forms of inherited hair loss, according to two studies published online this week in Nature Genetics. This discovery has the potential to lead to new treatments for hair loss and excessive hair.
Regina Betz and colleagues studied families in Saudi Arabia with hypotrichosis simplex, which causes progressive hair loss beginning in early childhood. They identified mutations in P2RY5, a gene encoding a receptor protein, and then went on to identify the molecule that activates the receptor as lysophosphatidic acid (LPA). LPA has been shown to promote hair growth in an animal model. Angela Christiano and colleagues studied families in Pakistan with 'woolly hair', characterized by sparse, dry and tightly curled hair over the entire scalp region. They also identified mutations in P2RY5, and show that it is expressed in the inner root sheath of hair follicles, implying a role for it in anchoring and shaping the growing hair shaft.
G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth
Sandra M Pasternack, Ivar von Kügelgen, Khalid Al Aboud, Young-Ae Lee, Franz Rüschendorf, Katrin Voss, Axel M Hillmer, Gerhard J Molderings, Thomas Franz, Alfredo Ramirez, Peter Nürnberg, Markus M Nöthen & Regina C Betz
Published online: 24 February 2008 | doi 10.1038/ng.84
Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair
Yutaka Shimomura, Muhammad Wajid, Yoshiyuki Ishii, Lawrence Shapiro, Lynn Petukhova, Derek Gordon & Angela M Christiano
Published online: 24 February 2008 | doi 10.1038/ng.100
