Press releases
Please quote Nature Genetics as the source of these items.
The April 2007 issue of Nature Genetics is available online.
April 2007
Genetic variant associated with triglyceride levels
Scientists have identified a rare genetic variant that is associated with lower levels of triglycerides, according to a study to be published online this week in Nature Genetics. Triglycerides are the stored form of fat, and elevated levels have been linked to risk of coronary artery disease.
The genetic contribution to common diseases takes the form of common variants - those found at frequencies greater than 5% - and rare variants. One strategy to identify rare variants is to resequence candidate genes in a number of individuals. Jonathan Cohen and colleagues report the first application of this strategy in a large population. The authors studied more than 3,500 individuals from the Dallas Heart Study, whose lipid and glucose metabolism has been characterized in detail. They sequenced the gene ANGPTL4, which encodes a hormone involved in lipid metabolism, in each of these individuals. They found that those individuals with the lowest levels of triglycerides had more variation in ANGPTL4, and one variant in particular was associated with a 27% reduction in triglyceride levels, compared with individuals who lack the variant.
This association was confirmed in two other large population-based studies. Overall, this study confirms the value of the resequencing approach in identifying genetic variants that influence disease-related traits.
Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL
Stefano Romeo, Len A Pennacchio, Yunxin Fu, Eric Boerwinkle, Anne Tybjaerg-Hansen, Helen H Hobbs & Jonathan C Cohen
Published online: 25 February 2007 | doi 10.1038/ng1984
Genetic variant protects against four infectious diseases
A genetic variant associated with protection against four different infectious diseases is described in an online study this week in Nature Genetics. The variant, which is significantly more likely to be found in individuals who remain disease-free, is estimated to reduce the risk of disease by approximately half.
Proteins called 'toll-like receptors' (TLRs) are involved in the immune response to a variety of pathogens. Adrian Hill and colleagues reasoned that variation in a protein called Mal, which is a critical mediator of signaling by TLRs, might make certain individuals more or less susceptible to infectious disease. The authors determined the frequency of 33 single-nucleotide variants in the gene encoding Mal in more than 6,000 individuals from Gambia, Kenya, the UK and Vietnam with or without pneumococcal disease, bacteremia, malaria and tuberculosis - diseases that account for more than 5 million deaths each year in the developing world.
A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis
Chiea C Khor, Stephen J Chapman, Fredrik O Vannberg, Aisling Dunne, Caroline Murphy, Edmund Y Ling, Angela J Frodsham, Andrew J Walley, Otto Kyrieleis, Amir Khan, Christophe Aucan, Shelley Segal, Catrin E Moore, Kyle Knox, Sarah J Campbell, Christian Lienhardt, Anthony Scott, Peter Aaby, Oumou Y Sow, Robert T Grignani, Jackson Sillah, Giorgio Sirugo, Nobert Peshu, Thomas N Williams, Kathryn Maitland, Robert J O Davies, Dominic P Kwiatkowski, Nicholas P Day, Djamel Yala, Derrick W Crook, Kevin Marsh, James A Berkley, Luke A J O'Neill & Adrian V S Hill
Published online: 25 February 2007 | doi 10.1038/ng1976
Mitochondrial point mutations do not limit lifespan
A large number of point mutations in mitochondria — the energy-producing units of the cell — do not have a direct link to the ageing process in mice, according to a study to be published online this week in Nature Genetics. While such mutations have been shown to accumulate during ageing in mice and humans, this result contradicts the notion that such mutations are causal factors in the aging process.
The widely debated mitochondrial theory of ageing postulates that the lifelong accumulation of mitochondrial DNA mutations contributes to the decline of tissue function observed in ageing. Lawrence Loeb and colleagues used a new, highly sensitive approach to determine the rate of single base-pair mutations in mitochondrial DNA in normal ageing mice, and in so-called ‘mitochondrial mutator mice’, which have a 500-fold greater mutation burden than normal mice. While the authors found that normal mice have an 11-fold increase in mitochondrial point mutations with age, the mutator mice did not have any obvious features of accelerated ageing, suggesting that the more modest mutation burden in normal mice is not likely to be contributing to the ageing process. It is important to note that this study does not exclude the possibility that large deletions of mitochondrial DNA contribute to ageing. For example, large deletions in mitochondrial DNA have been correlated with the impairment of certain neurons in aged individuals and in individuals with Parkinson disease.
Mitochondrial point mutations do not limit the natural lifespan of mice
Marc Vermulst, Jason H Bielas, Gregory C Kujoth, Warren C Ladiges, Peter S Rabinovitch, Tomas A Prolla & Lawrence A Loeb
Published online: 04 March 2007 | doi 10.1038/ng1988
Genetic variant associated with susceptibility to osteoarthritis
A variant in a gene called GDF5 is associated with the risk of developing osteoarthritis, a study published online this week in Nature Genetics.suggests. Osteoarthritis is the most common form of arthritis, affecting more than 20 million people in the United States.
Osteoarthritis is caused by the breakdown and loss of the cartilage in one or more joints during ageing, leading to swelling, pain, and limited mobility. Shiro Ikegawa and colleagues analyzed variation across the GDF5 gene and found that one particular variant was significantly more frequent in two independent populations of Japanese individuals with osteoarthritis of the hip compared to disease-free individuals. The same variant was also found to be significantly more frequent in both Japanese and Chinese individuals suffering from osteoarthritis of the knee. Depending on the study, the variant conferred 30%-80% additional risk of developing the disease. The authors showed that this variant probably reduces the amount of GDF5 produced. As GDF5 is a protein that is secreted by cells and is known to be involved in cartilage development, lower levels of GDF5 may affect the maintenance of cartilage in joints.
A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis
Yoshinari Miyamoto, Akihiko Mabuchi, Dongquan Shi, Toshikazu Kubo, Yoshio Takatori, Susumu Saito, Mikihiro Fujioka, Akihiro Sudo, Atsumasa Uchida, Seizo Yamamoto, Koichi Ozaki, Masaharu Takigawa, Toshihiro Tanaka, Yusuke Nakamura, Qing Jiang & Shiro Ikegawa
Published online: 25 March 2007 | doi 10.1038/ng2005
