Press releases
Please quote Nature Genetics as the source of these items.
The September 2007 issue of Nature Genetics is available online.
September 2007
Genetic risk factor for multiple sclerosis
A variant in a gene encoding a key regulator of the immune system increases the risk of multiple sclerosis, report two papers to be published online this week in Nature Genetics. Multiple sclerosis is a chronic and debilitating autoimmune disease in which neurons of the central nervous system become demyelinated, resulting in progressive neurodegeneration.
Susceptibility to multiple sclerosis is known to be strongly influenced by genetic factors, but little progress has been made in identifying them. Jonathan Haines and colleagues examined variants in three genes suspected to have a role in the disease, and found that variants in one of these genes, IL7R, were consistently more common in individuals with multiple sclerosis than in healthy control subjects. Their results were confirmed in four independent studies involving individuals of European descent from the United States, the United Kingdom and Belgium. Jan Hillert and colleagues, studying a large collection of individuals from Denmark, Finland, Norway and Sweden, observed a similar association between variants in IL7R and multiple sclerosis risk.
IL7R is present on the surface of some cells and can also be found in the blood serum. The variant thought to be responsible for conferring increased disease risk results in lower levels of the surface-bound form of IL7R and higher levels of the serum form, report Haines and colleagues. This change in the relative levels of the two forms of IL7R may alter the activity of the immune system, rendering individuals who carry the risk variant more susceptible to developing the disease.
Interleukin 7 receptor α chain (IL7R) shows allelic and functional association with multiple sclerosis
Simon G Gregory, Silke Schmidt, Puneet Seth, Jorge R Oksenberg, John Hart, Angela Prokop, Stacy J Caillier, Maria Ban, An Goris, Lisa F Barcellos, Robin Lincoln, Jacob L McCauley, Stephen J Sawcer, D A S Compston, Benedicte Dubois, Stephen L Hauser, Mariano A Garcia-Blanco, Margaret A Pericak-Vance & Jonathan L Haines, for the Multiple Sclerosis Genetics Group
Published online: 29 July 2007 | doi 10.1038/ng2103
Variation in interleukin 7 receptor α chain (IL7R) influences risk of multiple sclerosis
Frida Lundmark, Kristina Duvefelt, Ellen Iacobaeus, Ingrid Kockum, Erik Wallström, Mohsen Khademi, Annette Oturai, Lars P Ryder, Janna Saarela, Hanne F Harbo, Elisabeth G Celius, Hugh Salter, Tomas Olsson & Jan Hillert
Published online: 29 July 2007 | doi 10.1038/ng2106
How West Nile virus became dangerous
A single causative mutation has been identified in the virulent strain of West Nile virus that has been responsible for deadly outbreaks of human encephalitis in recent years, according to a paper online this week in Nature Genetics.
West Nile virus is a mosquito-borne virus that is transmitted between avian hosts and mosquitoes, and until the mid 1990s was associated with only mild infections of humans in Africa and the Middle East. More severe outbreaks of encephalitis were reported in Romania in 1996, and subsequently in Israel, Tunisia, Russia, and North America.
Aaron Brault and colleagues sequenced the genomes of West Nile virus strains that have been sampled globally in recent years, and found that a single mutation in a gene encoding an enzyme called a helicase arose independently on at least three separate occasions in strains associated with outbreaks of disease. When a poorly virulent strain from Kenya was engineered to contain the helicase mutation, it was found to replicate more rapidly and to cause death of inoculated American crows at a much higher rate than that of the original Kenyan virus. The authors also provide evidence that the helicase mutation was positively selected, which they say highlights the potential for viruses like West Nile to adapt rapidly to changing environments, with unpredictable consequences for human health.
A single positively selected West Nile viral mutation confers increased virogenesis in American crows
Aaron C Brault, Claire Y-H Huang, Stanley A Langevin, Richard M Kinney, Richard A Bowen, Wanichaya N Ramey, Nicholas A Panella, Edward C Holmes, Ann M Powers & Barry R Miller
Published online: 12 August 2007 | doi 10.1038/ng2097
Prevention and treatment of craniosynostosis
Two successful strategies for the prevention and treatment of craniosynostosis — premature fusion of the sutures in the skull — are reported online this week in Nature Genetics. At least one of the approaches may be testable in humans in the near term. Craniosynostosis is caused by the sutures of the skull closing too early in infancy, which affects normal brain and skull growth. It occurs in approximately 1 of every 2,500 live births. Apert syndrome, a rare but quite severe form of craniosynostosis, is caused in most cases by a specific mutation in a cell-surface receptor called FGFR2.
Chu-Xia Deng and colleagues created a mouse model of Apert syndrome that bears one of the most common FGFR2 mutations seen in humans. When these mice were crossed with mice expressing a 'short hairpin' RNA molecule specifically designed to block expression of the mutant form of FGFR2, the offspring that carry the FGFR2 mutation developed normally. The authors also report the involvement in the disease of an enzyme called ERK, which is regulated by FGFR2. When they injected a drug that inhibits ERK activity into pregnant mice carrying the FGFR2 mutation, the offspring showed no signs of Apert syndrome. Moreover, when the drug was injected at the onset of the disease during the early postnatal period, at least some of the treated mice maintained a normal appearance, although the treatment’s effectiveness was greater in male than in female mice.
Drugs similar to those used in this study are already being tested in clinical trials as anticancer drugs, and may now have additional applications in the prevention and treatment of birth defects such as craniosynostosis.
RNA interference and inhibition of MEK-ERK signaling prevent abnormal skeletal phenotypes in a mouse model of craniosynostosis
Vivek Shukla, Xavier Coumoul, Rui-Hong Wang, Hyun-Seok Kim & Chu-Xia Deng
Published online: 12 August 2007 | doi 10.1038/ng2096
Positive selection during human evolution
Sequences in the human genome that have undergone positive selection are found in abundance in regions that regulate the expression of genes involved in neural or nutritional processes, suggests a paper online this week in Nature Genetics. The study provides some of the first large-scale evidence that the evolution of some human-specific traits can be traced to changes in gene regulatory (promoter) regions.
Cognitive, behavioural and dietary differences are among the most obvious differences between humans and the great apes. Although one might expect that genes involved in these processes would show evidence of positive natural selection in humans since the most recent common ancestor of humans and chimpanzees, there is little evidence to support this.
Ralph Haygood and colleagues compared probable promoter regions for more than 6,000 genes in the human, chimpanzee and macaque genomes. They generated statistics to identify those promoters that likely had undergone positive selection in the human genome. At least 250 such promoters were found. Although they represent several functional categories, prominent among them are promoters linked to genes involved in neural development and function, including axon guidance, synapse formation and neurotransmission in the brain. Nutrition-related genes include a large number involved in glucose metabolism.
Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution
Ralph Haygood, Olivier Fedrigo, Brian Hanson, Ken-Daigoro Yokoyama & Gregory A Wray
Published online: 12 August 2007 | doi 10.1038/ng2104
