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Predicting the risk of a common fungal infection after stem cell transplantation
June 20, 2008In silico genetic analysis in mice has led to the discovery of a gene affecting susceptibility to a severe fungal infection in transplant recipients. In a study published June 20th in the open-access journal PLoS Genetics, investigators from Duke University Medical Center, the National Institute of Environmental Health Sciences, Roche Palo Alto, the Fred Hutchinson Cancer Research Center, and the National Jewish Medical and Research Center found that genetic variation within the plasminogen gene in mice and men affects susceptibility to a severe and life-threatening fungal infection.
Invasive infection with Aspergillus fumigatus is a common and life-threatening infection among severely immunocompromised individuals. Despite aggressive surveillance and prophylaxis, its incidence in hematopoietic stem cell transplant recipients hovers around 10%, and the three-month mortality rate is approaching 30%.
Lead investigators Aimee Zaas and David Schwartz examined the susceptibility of different inbred mouse strains for developing invasive aspergillosis after receiving immunosuppressive therapy. The inbred strains exhibited significant and reproducible differences in survival after inhalational exposure to the fungus.
Co-author Gary Peltz and colleagues recently developed an in silico method for genetic analysis in mice that was used to analyze this survival data, which led to the rapid identification of genetic variation within the plasminogen gene as a potential susceptibility factor. Therefore, it is possible that polymorphisms in human plasminogen may also affect susceptibility. Analysis of a cohort of bone marrow transplant recipients indicated that a human plasminogen allele also affects the risk of contracting this disease.
Peltz, who is now at Stanford University, stated: "This is the first study that used a multi-species genetic mapping approach to identify genetic susceptibility factors for a severe infection."
Identification of a genetic polymorphism that influences infection after transplantation has important implications for pre and post transplant care, and possibly for the management of other immune-compromised patients. Genetic testing could identify high-risk individuals who may benefit from the use of broad-spectrum antifungal agents or enhanced monitoring for infection. It is important to emphasize, however, that further research and evaluation is required before clinical applications can be developed.
http://www.plosgenetics.org/doi/pgen.1000101
Public Library of Science
Co-author Gary Peltz and colleagues recently developed an in silico method for genetic analysis in mice that was used to analyze this survival data, which led to the rapid identification of genetic variation within the plasminogen gene as a potential susceptibility factor. Therefore, it is possible that polymorphisms in human plasminogen may also affect susceptibility. Analysis of a cohort of bone marrow transplant recipients indicated that a human plasminogen allele also affects the risk of contracting this disease.
Peltz, who is now at Stanford University, stated: "This is the first study that used a multi-species genetic mapping approach to identify genetic susceptibility factors for a severe infection."
Identification of a genetic polymorphism that influences infection after transplantation has important implications for pre and post transplant care, and possibly for the management of other immune-compromised patients. Genetic testing could identify high-risk individuals who may benefit from the use of broad-spectrum antifungal agents or enhanced monitoring for infection. It is important to emphasize, however, that further research and evaluation is required before clinical applications can be developed.
http://www.plosgenetics.org/doi/pgen.1000101
Public Library of Science
Genetic Analysis Current Events and Genetic Analysis News RSSGenetic analysis helps dissect molecular basis of cardiovascular disease
Using highly precise measurements of plasma lipoprotein concentrations determined by nuclear magnetic resonance spectroscopy (NMR), researchers led by Daniel Chasman at Brigham and Women's Hospital and Harvard Medical School in Boston, MA, the Framingham Heart Study in Framingham, and the PROCARDIS consortium in Stockholm, Sweden and Oxford, England performed genetic association analysis across the whole genome among 17,296 women of European ancestry from the Women's Genome Health Study.
Largest gene study of childhood IBD identifies 5 new genes
In the largest, most comprehensive genetic analysis of childhood-onset inflammatory bowel disease (IBD), an international research team has identified five new gene regions, including one involved in a biological pathway that helps drive the painful inflammation of the digestive tract that characterizes the disease.
FDA approved leukemia drugs shows promise in ovarian cancer cells
The drug Sprycel, approved for use by the U.S. Food and Drug Administration in patients with chronic myeloid leukemia, significantly inhibited the growth and invasiveness of ovarian cancer cells and also promoted their death, a study by researchers with UCLA's Jonsson Comprehensive Cancer Center found.
Blood test identifies women at risk from Alzheimer's
Middle-aged women with high levels of a specific amino acid in their blood are twice as likely to suffer from Alzheimer's many years later, reveals a thesis from the Sahlgrenska Academy at the University of Gothenburg, Sweden.
Conserving historic apple trees
The apple trees of yesteryear are slowly disappearing. Many apple varieties common in the United States a century ago can no longer be found in today's orchards and nurseries.
Orphan army ants join nearby colonies
Colonies of army ants, whose long columns and marauding habits are the stuff of natural-history legend, are usually antagonistic to each other, attacking soldiers from rival colonies in border disputes that keep the colonies separate.
The first men and women from the Canary Islands were Berbers
A team of Spanish and Portuguese researchers has carried out molecular genetic analysis of the Y chromosome (transmitted only by males) of the aboriginal population of the Canary Islands to determine their origin and the extent to which they have survived in the current population.
Autism Speaks' genetic resource exchange, tissue program support findings published in Nature
Autism Speaks' Autism Genetic Resource Exchange (AGRE) and the Autism Tissue Program (ATP) continue to play an integral role in continuing genetic research and new findings in the complex autism inheritance and causation puzzle.
Scientists join forces to explain HIV spread in Central and East Africa
Scientists studying biology and geography may seem worlds apart, but together they have answered a question that has defied explanation about the spread of the HIV-1 epidemic in Africa.
Research Team Finds First Evolutionary Branching for Bilateral Animals
In the most computationally intensive phylogenetic analysis to date, an international research team led by Brown University has found the first evolutionary branching for bilateral animals.
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