Press releases
Please quote Nature Genetics as the source of these items.
The June 2007 issue of Nature Genetics is available online.
June 2007
Gene combinations influence AIDS progression
Different combinations of genetic variants of two modulators of the innate human immune system strongly influence AIDS progression in HIV-positive individuals, according to a study to be published online this week in Nature Genetics.
Natural killer cells are part of the antiviral immune response, and their activity is controlled by receptors called KIRs that are present on the cell surface. The KIR receptors that inhibit natural killer cell activity (KIR3DL1) are triggered by HLA-B molecules, which are presented by other cells of the immune system. Mary Carrington and colleagues examined variation in the genes encoding KIR3DL1 and HLA-B in more than 1,500 HIV-positive individuals, and found that particular combinations of variants conferred protection against AIDS progression.
These results may explain at least part of the variability in progression of the disease in infected individuals. The authors also note that the observed rapid evolution of these genes may be driven by pathogens such as HIV.
Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1
Maureen P Martin, Ying Qi, Xiaojiang Gao, Eriko Yamada, Jeffrey N Martin, Florencia Pereyra, Sara Colombo, Elizabeth E Brown, W Lesley Shupert, John Phair, James J Goedert, Susan Buchbinder, Gregory D Kirk, Amalio Telenti, Mark Connors, Stephen J O'Brien, Bruce D Walker, Peter Parham, Steven G Deeks, Daniel W McVicar & Mary Carrington
Published online: 13 May 2007 | doi 10.1038/ng2035
Gene copy number and risk of autoimmunity
Individuals with fewer than two copies of the gene FCGR3B are more susceptible to a variety of autoimmune disorders, including lupus, according to a study to be published online this week in Nature Genetics.
Evidence is accumulating that, in addition to gene mutations, variation in the actual number of copies of individual genes can influence susceptibility to common diseases. It was previously shown that variation in the copy number of FCGR3B, a cell-surface receptor that contributes to the protective functions of the immune system, is associated with susceptibility to a kidney disease called glomerulonephritis. Timothy Aitman and colleagues now report that FCGR3B copy number variation is associated more broadly with autoimmune disorders, including lupus, microscopic polyangiitis, and Wegener's granulomatosis. The small group of individuals who have no copies of FCGR3B have a dramatically elevated risk of autoimmune disease. This is among the first demonstrations that common naturally occurring variation in gene copy number can influence human susceptibility to disease.
FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity
Manuela Fanciulli, Penny J Norsworthy, Enrico Petretto, Rong Dong, Lorraine Harper, Lavanya Kamesh, Joanne M Heward, Stephen C L Gough, Adam de Smith, Alexandra I F Blakemore, Philippe Froguel, Catherine J Owen, Simon H S Pearce, Luis Teixeira, Loic Guillevin, Deborah S Cunninghame Graham, Charles D Pusey, H Terence Cook, Timothy J Vyse & Timothy J Aitman
Published online: 21 May 2007 | doi 10.1038/ng2046
DNA breakage in living color
Spontaneous breaks of replicating DNA in bacteria occur at a rate much lower than suspected, according to a study to be published online this week in Nature Genetics. This is the first direct measurement of DNA breakage in normal living cells, and suggests that the potential for such damage to cause larger chromosomal rearrangements is much greater than previously realized.
The cellular machinery that replicates DNA sometimes stalls. While these stalled 'replication forks' can be resolved by cleaving the DNA, which allows replication to start again, the frequency of these spontaneous breaks has been unknown. Jeanine Pennington and Susan Rosenberg devised a way to visualize individual bacteria (E. coli) with such a break by inserting a gene encoding a green fluorescent protein that would be triggered by the cell’s response to DNA damage.
The authors observed that approximately 1% of the cells in their experiment had at least one spontaneous break per generation. Previous reports based on indirect measurements had suggested a rate 20- to 100-fold higher. This low rate of spontaneous breakage suggests that each break must be a much more potent cause of the dangerous genetic instability that can result from the attempt to repair them. The authors suggest that cells, including those of higher organisms, have likely developed robust ways to avoid the creation of such DNA breaks.
Spontaneous DNA breakage in single living Escherichia coli cells
Jeanine M Pennington & Susan M Rosenberg
Published online: 27 May 2007 | doi 10.1038/ng2051
