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Archive - Mar 6, 2011

13 Gene Regions Newly Associated with Coronary Atherosclerosis in Massive Study

Thirteen new gene regions have been convincingly associated with coronary atherosclerosis in a massive, new, international genetics study involving investigators from the Stanford University School of Medicine and researchers from other major institutions around the world. The results of the study, published online March 6 in Nature Genetics, provide 13 vital new clues on the etiology of this disease, the most common cause of death worldwide. The study doubles the number of gene regions previously known to predispose people to this condition. Coronary atherosclerosis is the process by which plaque builds up in the wall of heart vessels, eventually leading to chest pain and potentially lethal heart attacks. The study was conducted by an international consortium, which pooled resources to analyze data from 14 genome-wide association studies. Consortium investigators examined the complete genetic profiles of more than 22,000 people of European descent with coronary heart disease or a heart attack history and 60,000 healthy people — close to 10 times more than the next-largest whole-genome study to date. "These new discoveries will allow scientists worldwide to eventually better understand the root causes of coronary atherosclerosis, possibly leading to important new drug therapies that may profoundly reduce the risk of having a heart attack," said Dr. Thomas Quertermous, the William G. Irwin Professor in Cardiovascular Medicine at Stanford. Dr. Quertermous is the principal investigator of the Stanford/Kaiser ADVANCE study of heart disease, which joined this consortium early in its formation. Investigators were able to examine an average of 2.5 million common single nucleotide polymorphisms, or SNPs, in each of the 14 genome-wide association studies. SNPs are genetic variants at specific locations on individual chromosomes.

Gene for Rare Osteoporosis Disorder Identified

Scientists have identified a single mutated gene that causes Hajdu-Cheney syndrome (HCS), a disorder of the bones causing progressive bone loss and osteoporosis. The study, published online in Nature Genetics on March 6, 2011, gives vital insight into possible causes of osteoporosis and highlights the identified gene (NOTCH2) as a potential target for treating the condition. There are only 50 reported cases of HCS, of which severe osteoporosis is a main feature. Osteoporosis is a condition leading to reduction in bone strength and susceptibility to fractures. It is the most common bone disease, with one in two women and one in five men over 50 in the UK fracturing a bone because of the condition. This represents a major public health problem yet, until this study, possible genetic causes of osteoporosis have been poorly understood. The team of researchers, led by the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre (BRC) at King's College London and Guy's and St Thomas', set out to investigate the genetic cause of HCS in order to detect clues to the role genes might play in triggering osteoporosis. Using a cutting edge technique for identifying disease-causing genes, known as exome sequencing, the team was able to identify NOTCH2 as the causative gene using DNA from just three unrelated HCS patients. The team then confirmed their findings in an additional 12 affected families, 11 of whom had an alteration in the identical portion of the same gene. Senior author Professor Richard Trembath, Head of King's College London's Division of Genetics and Molecular Medicine and Medicine Director of the NIHR BRC, said: "Up until now, we knew very little about the genetic mechanisms of severe bone disease.

Cryo-Microscope Allows High-Res 3-D Model of Salmonella’s Needle Complex

Some of the most dread diseases in the world such as plague, typhoid, and cholera are caused by bacteria that have one thing in common: they possess an infection apparatus which is a nearly unbeatable weapon. When attacking a cell of the body, they develop numerous hollow-needle-shaped structures that project from the bacterial surface. Through these needles, the bacteria inject signal substances into the host cells, which re-program these cells and thereby overcome their defense. The pathogens can then invade the cells unimpeded and in large numbers. The biochemist and biophysicist Dr. Thomas Marlovits, a group leader at the Vienna Institutes IMP (Research Institute of Molecular Pathology) and IMBA (Institute of Molecular Biotechnology) has been occupied for several years with the infection complex of salmonellae. As early as in 2006 Dr. Marlovits showed how the needle complex of Salmonella typhimurium develops. Together with his doctoral student Oliver Schraidt, he has now been able to demonstrate the three-dimensional structure of this complex at extremely high resolution. The team was able to show details with dimensions of just 5 to 6 angstroms, which are nearly atomic orders of magnitude. Their work is presented in the March 4, 2011 issue of Science. Never before has the infection tool of salmonellae been presented in such precision. This was achieved by the combined use of high-resolution cryo-electron microscopy and specially developed imaging software. "Austria's coolest microscope" makes it possible to shock-freeze biological samples at minus 196 degrees centigrade and view them in almost unchanged condition.