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Globetrotting black rat genes reveal spread of humans and diseases

02-01-2008 · EurekAlert!

DNA of the common black rat has shed light on the ancient spread of rats, people and diseases around the globe. Studying the mitochondrial DNA of 165 black rat specimens from 32 countries around the world, an international team of scientists has identified six distinct lineages in the black rat's family tree, each originating from a different part of Asia.

Keywords: globetrotting, black, rat, genes, reveal, spread, humans, diseases, gene, human, disease

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Advance in understanding of blood pressure gene could lead to new treatments
02-04-2007 · EurekAlert!
Research by scientists at UCL (University College London) has clearly demonstrated for the first time the structure and function of a gene crucial to the regulation of blood pressure. The discovery could be important in the search for new treatments for illnesses such as heart disease, the UK's biggest killer. In a paper published online today in Nature Medicine, the team, led by Professor Patrick Vallance and Dr James Leiper, UCL Department of Medicine, reveal the role of the human gene dimethylarginine dimethylaminohydrolase (DDAH), showing that loss of DDAH activity disrupts nitric oxide (NO) production. NO is critical in the regulation of blood pressure, nervous system functions and the immune system. The role of DDAH is to break down modified amino acids (Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA)) that are produced by the body and have been shown to inhibit NO synthase. These molecules accumulate in various disease states including diabetes, renal failure and pulmonary and systemic hypertension, and their concentration in plasma (the fluid component of blood) is strongly predicative of cardiovascular disease and death. In a healthy human body, the majority of ADMA is eliminated through active metabolism by DDAH. Scientists have hypothesised that if DDAH function is impaired, NO production is reduced, and that this could be an important feature of increased cardiovascular risk. To examine this pathway in more detail, the researchers deleted the DDAH gene in mice. These mice went on to develop hypertension, or high blood pressure. They also designed specific inhibitors (small molecules) which bind to the active site of human DDAH. These small molecule inhibitors also induced hypertension in mice, confirming the importance of DDAH in the regulation of blood pressure. Dr Leiper, UCL Medicine, said: “These genetic and chemical approaches to disrupt DDAH showed remarkably consistent results, and provide compelling evidence that loss of DDAH function increases the concentration of ADMA and thereby disrupts vascular NO signalling. “There has been considerable scientific interest in this pathway and the role of ADMA as a novel risk factor, but so far there's been little evidence to support the idea that it's a cause of disease, rather than just a marker. Genes and their pathways are crucial to our understanding of cardiovascular disease and a better understanding of DDAH-1 could lead to important new treatments. “It could help us to establish if genetic variation predisposes certain people to these diseases, or whether environmental factors exert some of their effects through modulation of DDAH activity. “Our research also shows that this pathway could be harnessed therapeutically to limit production of NO in certain situations where too much nitric oxide is a bad thing; for example, hypotension and septic shock. These are some of the biggest problems in intensive care medicine and there is a huge unmet need for drug treatments.” The study, which was carried out at UCL's Rayne Institute, was funded by grants from the British Heart Foundation, the Wellcome Trust and the Medical Research Council. Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation, said: "The unexpected finding in the 1980s that a simple gas, nitric oxide (NO), is made by cells in the blood vessel wall and is a powerful control of blood vessel relaxation led to the award of the Nobel Prize in 1998 to its discoverers. "More recently, there has been increasing evidence that impairment of NO production is likely to be an important factor in the development of heart and circulatory disease, but the mechanisms responsible are not fully understood. "This study suggests for the first time that the loss of the activity of the enzyme DDAH-1 leads to reduced NO production and may cause heart and circulatory disease. These findings are likely to be important in the search for new ways to optimise the health of our blood vessels." ### Notes for Editors 1. For more information, please contact Ruth Metcalfe in the UCL Media Relations Office on tel: +44 (0)20 7679 9739, mobile: +44 (0)7990 675 947, out of hours: +44 (0)7917 271 364, e-mail: r.metcalfe@ucl.ac.uk2. 'Disruption of methylarginine metabolism impairs vascular homeostasis' is published in the February issue of the journal Nature Medicine. Advance online publication is embargoed to 18.00 GMT (13.00 US Eastern) Sunday 4 February 2007. Journalists can obtain copies of the paper by contacting the UCL Media Relations Office.3. The study was funded by the British Heart Foundation, the Wellcome Trust and the Medical Research Council. About UCL Founded in 1826, UCL was the first English university established after Oxford and Cambridge, the first to admit students regardless of race, class, religion or gender, and the first to provide systematic teaching of law, architecture and medicine. In the government's most recent Research Assessment Exercise, 59 UCL departments achieved top ratings of 5* and 5, indicating research quality of international excellence. UCL is the fourth-ranked UK university in the 2006 league table of the top 500 world universities produced by the Shanghai Jiao Tong University. UCL alumni include Mahatma Gandhi (Laws 1889, Indian political and spiritual leader); Jonathan Dimbleby (Philosophy 1969, writer and television presenter); Junichiro Koizumi (Economics 1969, Prime Minister of Japan); Lord Woolf (Laws 1954, Lord Chief Justice of England & Wales); Alexander Graham Bell (Phonetics 1860s, inventor of the telephone), and members of the band Coldplay.
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Fruit fly gene research may shed light on human disease processes
03-27-2007 · EurekAlert!
Those small fruit flies buzzing around your bananas are more than pests -- they may be allies in a fruitful search for clues to human diseases caused when genes malfunction.
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The importance of gene regulation for common human disease
09-16-2007 · EurekAlert!
A new study published in Nature Genetics on Sunday Sept. 16, 2007, shows that common, complex diseases are more likely to be due to genetic variation in regions that control activity of genes, rather than in the regions that specify the protein code. This surprising result comes from a study at the Wellcome Trust Sanger Institute of the activity of almost 14,000 genes in 270 DNA samples collected for the HapMap Project.
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Search for the 'on' switches may reveal genetic role in development and disease
01-24-2008 · EurekAlert!
A new resource that identifies regions of the human genome that regulate gene expression may help scientists learn about and develop treatments for a number of human diseases, according to researchers at Duke's Institute for Genome Sciences & Policy.
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Brown scientists map structure of DNA-doctoring protein complex
12-06-2006 · EurekAlert!
Mobile DNA, which inserts foreign genes into target cells, is a powerful force in the march of evolution and the spread of disease. Working with the lambda virus and E. coli bacteria, Brown University biologists have solved the structure of a six-protein complex critical to performing this gene-grafting surgery. The technique they developed could be used to reveal the structure of other critical protein complexes, landing the work on the cover of Molecular Cell.
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Gene found for rare disorder may reveal new pathway in mental retardation
02-05-2007 · EurekAlert!
Studying mutations that give rise to a rare genetic disease, genetics researchers have identified a novel biological pathway that may have a broader role during human development, potentially in cases of mental retardation and autism. An international team of researchers identified two genes that contribute to Cornelia deLange syndrome, a multisystem genetic disease that affects an estimated one in 10,000 children.
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University of Washington researchers play leading role in major study of human genome function
06-13-2007 · EurekAlert!
Scientists at the University of Washington and other members of an international consortium have completed a multi-year research effort that dramatically boosts understanding of how the human genome functions. While previous studies of the human genome have focused mainly on genes, this study provides insight into non-gene sequences and "regulatory elements" that control genes and may play a role in many common diseases.
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A genetic 'gang of 4' drives spread of breast cancer
04-11-2007 · EurekAlert!
Studies of human tumor cells implanted in mice have shown that the abnormal activation of four genes drives the spread of breast cancer to the lungs. The new studies by Howard Hughes Medical Institute researchers reveal that the aberrant genes work together to promote the growth of primary breast tumors. Cooperation among the four genes also enables cancerous cells to escape into the bloodstream and penetrate through blood vessels into lung tissues.
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Brown team finds crucial protein role in deadly prion spread
01-23-2007 · EurekAlert!
Brown University biologists have made another major advance toward understanding the deadly work of prions, the culprits behind fatal brain diseases such as mad cow and their human counterparts. In new work published online in PLoS Biology, researchers show that the protein Hsp104 must be present and active for prions to multiply and cause disease.
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Not just humans benefit from animal biotechnology
10-24-2007 · EurekAlert!
Laboratory animals are the source of major discoveries and breakthroughs in biology, not just in tackling disease but also unravelling fundamental molecular processes. Delegates at a recent research conference organized by the European Science Foundation and Wellcome Trust heard how technology capable of analysing animal genes across the whole genome is yielding many benefits for agriculture and human society.
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