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Archive - 2011

September 7th

Endangered Horse Has Ancient Origins and Rich Genetic Diversity

An endangered species of horse -- known as Przewalski's horse -- is much more distantly related to the domestic horse than researchers had previously hypothesized, reports a team of investigators led by Dr. Kateryna Makova, a Penn State University associate professor of biology. The scientists tested the portion of the genome passed exclusively from mother to offspring -- the mitochondrial DNA -- of four Przewalski's horse lineages and compared the data to DNA from the domestic horse (Equus caballus). They concluded that, although previous scientists had assumed that Przewalski's horse and the domestic horse had diverged around the time that horses were domesticated -- about 6,000 to 10,000 years ago -- the real time of the two species' divergence from one another is much more ancient. The data gleaned from the study also suggest that present-day Przewalski's horses have a much more diverse gene pool than previously hypothesized. The new study's findings could be used to inform conservation efforts to save the endangered horse species, of which only 2,000 individuals remain in parts of China and Mongolia, and in wildlife reserves in California and the Ukraine. The paper will be published in the journal Genome Biology and Evolution. It was first published online, before print, on July 29, 2011. Przewalski's horse -- a stocky, short-maned species named after a Russian explorer who first encountered the animal in the wild -- became endangered during the middle of the last century when the species experienced a population bottleneck -- an evolutionary event in which many or most members of a population or a species die. "Sadly, this bottleneck was the result of human activity," Dr. Makova explained.

September 6th

Next-Gen Sequencing Reveals a Gene for Mitochondrial Disease

In Leigh syndrome, infants are born apparently healthy only to develop movement and breathing disorders that worsen over time, often leading to death by the age of 3. The problem is that the mitochondria responsible for powering their cells can't keep up with the demand for energy in their developing brains. Now, researchers reporting in the September issue of Cell Metabolism, a Cell Press publication, have discovered a new genetic defect that can lead to the disease. The findings were made by sequencing a subset of about 1,000 genes encoding proteins active in the mitochondria in just two individuals with Leigh syndrome. "This shows the huge potential of sequencing technologies to improve diagnosis," says Dr. David Thorburn of Murdoch Childrens Research Institute in Australia. "It's an all-comers approach that can be applied to individuals, even with no family history." Leigh syndrome is the most common recognized mitochondrial disease of childhood, and the new genetic discovery adds to a growing list of about 40 genes known to cause Leigh syndrome when mutated. The gene the researchers uncovered encodes an enzyme active in mitochondria known as MTFMT (for mitochondrial methionyl-tRNA formyltransferase). (Mitochondria carry DNA of their own and their operation depends on a combination of proteins encoded locally and others encoded in the nuclear genome of a cell and imported.) The MTFMT enzyme encoded in the mitochondrial DNA is responsible for converting a transfer RNA (tRNA) into a form used to initiate protein translation. Without that enzyme, mitochondria fail to translate proteins efficiently leading to the symptoms recognized as Leigh syndrome. Studies in patient skin cells showed that the defects in translation could be corrected by replacing the MTFMT gene.

September 1st

First Lizard Genome Sequenced

The green anole lizard is an agile and active creature, and so are elements of its genome. This genomic agility and other new clues have emerged from the full sequencing of the lizard's genome and may offer insights into how the genomes of humans, mammals, and their reptilian counterparts have evolved since mammals and reptiles parted ways 320 million years ago. The researchers who completed this sequencing project reported their findings August 31, 2011, online in the journal Nature. The green anole lizard (Anolis carolinensis) – a native of the Southeastern United States – is the first non-bird species of reptile to have its genome sequenced and assembled. Broad Institute researchers have assembled and analyzed more than 20 mammalian genomes – including those of some of our closest relatives – but the genetic landscape of reptiles remains relatively unexplored. "Sometimes you need to be at a certain distance in order to learn about how the human genome evolved," said Dr. Jessica Alföldi, co-first author of the paper and a research scientist in the vertebrate genome biology group at the Broad Institute. "You have to look out further than you were looking previously." Lizards are more closely related to birds – which are also reptiles – than to any of the other organisms whose genomes have been sequenced in full. Like mammals, birds and lizards are amniotes, meaning that they are not restricted to laying eggs in water. "People have been sequencing animals from different parts of the vertebrate tree, but lizards had not been previously sampled," said Dr. Kerstin Lindblad-Toh, scientific director of vertebrate genome biology at the Broad and senior author of the Nature paper.

August 31st

Modified Toxin from Sea Bacteria Shows Potential As Anti-Colon-Cancer Drug

University of Florida (UF) researchers have modified a toxic chemical produced by tiny marine microbes and successfully deployed it against laboratory models of colon cancer. In an article published online on August 31, 2011 in ACS Medicinal Chemistry Letters, UF medicinal chemists describe how they took a generally lethal byproduct of marine cyanobacteria and made it more specifically toxic — to cancer cells. When the scientists gave low doses of the modified compound to mice with a form of colon cancer, they found that it inhibited tumor growth without the overall poisonous effect of the natural product. Even at relatively high doses, the agent was effective and safe. "Sometimes nature needs a helping human hand to further optimize these products of evolution to treat human diseases," said the article’s senior author, Dr. Hendrik Luesch, an associate professor of medicinal chemistry at UF's College of Pharmacy. "Based on what we learned about apratoxins' mechanism of action, we knew this compound class had great potential for use in anticancer therapies; however, the natural product itself is too toxic to become a therapeutic." The researchers synthesized several apratoxin compounds that were similar to the original, except for slight differences in composition, designing one that proved to be extremely potent against the cancer cells in cultures and in mice, but without the overwhelming toxicity. The compound acts as a single agent to reduce levels of two types of proteins that are targeted by cancer research labs around the world — growth factors, and enzymes called tyrosine kinases, which act as receptors for the growth factors. Known as apratoxin S4, the compound strips colon cancer cells of their ability to both secrete and use naturally occurring factors that fuel growth — something that Dr. Luesch, postdoctoral chemist Dr.

Genetic Condition May Underlie Many Cases of Personal Bad Odor

Scientists from the Monell Center in Philadelphia report that approximately one third of patients with unexplained body malodor production test positive for the metabolic disorder trimethylaminuria (TMAU). A definitive diagnosis offers relief to these individuals, as symptoms of TMAU can hinder social and workplace interactions and cause psychological distress. But once the disease is identified, these debilitating symptoms can be ameliorated using changes in diet and other approaches. "Health care professionals must arrive at a correct diagnosis to suggest appropriate treatment," said study lead author Dr. Paul M. Wise, a sensory psychologist at Monell. "This research raises awareness of both the disease and also the proper methods of diagnosis and treatment." TMAU is a genetically-transmitted disease that inhibits the ability of an enzyme to metabolize or transform trimethylamine (TMA), a chemical compound produced naturally from many foods. TMA has a foul, fishy odor. At lower concentrations, it may be perceived as unpleasant or "garbage-like." Production of TMA is associated with foods rich in the dietary constituent, choline. Such foods include eggs, certain legumes, wheat germ, saltwater fish, and organ meats. The distressing symptoms of TMAU stem from the accumulation of excess TMA – and its associated unpleasant odor – which is then excreted from the body in urine, sweat, saliva, and breath. Importantly, TMA production and associated odor symptoms depend on what foods have been recently eaten and therefore may occur in irregular and seemingly unpredictable intervals. This makes the disease difficult to diagnose, as patients can appear to be odor-free when they consult a health professional.

August 30th

Black Death Pathogen Likely Extinct

The so-called "Black Death," a plague that ravaged Europe between the years of 1347 and 1351, was likely caused by a now-extinct version of the Yersinia pestis bacterium, according to results of a study published online on August 29, 2011 in PNAS. Dr. Hendrik Poinar, from McMaster University in Canada, and colleagues made this determination after analyzing the DNA of 109 human skeletal remains excavated at the East Smithfield mass burial site in London, England. The researchers also studied DNA from the remains of 10 humans unearthed at St. Nicholas Shambles, a site pre-dating the Black Death medieval plague. Individuals buried at East Smithfield harbored Y. pestis genes, which the authors sequenced to form among the oldest and longest genetic assemblages from an ancient pathogen. The genetic sequence differs from the sequences of other known versions of Y. pestis, the authors found, suggesting that the pathogen responsible for the Black Death is likely extinct. Because modern plague continues to affect an estimated 2,000 people per year worldwide, the authors suggest that earlier forms of the disease may yield clues about the pathogen's evolutionary history and possibly reveal how it caused such widespread devastation during the Black Death period. [Press release] [PNAS abstract]

First Kangaroo Genome Sequence Determined

Kangaroos form an important niche in the tree of life, but until now their DNA had never been sequenced. In an article published August 19, 2011 in BioMed Central's open access journal Genome Biology, an international consortium of researchers present the first kangaroo genome sequence – that of the tammar wallaby species – and find hidden in their data the gene that may well be responsible for the kangaroo's characteristic hop. "The tammar wallaby sequencing project has provided us with many possibilities for understanding how marsupials are so different to us," says Professor Marilyn Renfree of The University of Melbourne. Dr. Renfree was one of the lead researchers on the project, which was conducted by an international consortium of scientists from Australia, USA, Japan, England, and Germany. Tammar wallabies have many intriguing biological characteristics. For example, the 12-month gestation includes an 11-month period of suspended animation in the womb. At birth, the young weigh only half a gram, and spend 9 months in the mother's pouch, where the newborn babies reside for protection. Researchers hope that the genome sequence will offer clues as to how tammar wallaby genes regulate these fascinating features of kangaroo life. In addition to zeroing in on the "hop" genes, other exciting discoveries from the genome include the 1,500 smell detector genes responsible for the tammar wallaby's excellent sense of smell, and genes that make antibiotics in the mother's milk in order to protect kangaroo newborns from E. coli and other harmful bacteria. As Dr. Renfree explains, lessons to be learned from the tammar wallaby genome "may well be helpful in producing future treatments for human disease." The first kangaroo genome is a key milestone in the study of mammalian evolution.

August 18th

Vitamin C Treatment Dissolves Protein Aggregates in Alzheimer’s Disease Model

Researchers at Lund University in Sweden, and collaborating institutions, have discovered a new function for vitamin C. Treatment with vitamin C can dissolve the toxic protein aggregates that build up in the brain in an animal model of Alzheimer's disease. The research findings were presented in the August 5, 2011 issue of the Journal of Biological Chemistry. The brains of people with Alzheimer's disease contain lumps of so-called amyloid plaques which consist of misfolded protein aggregates. They cause nerve cell death in the brain and the first nerves to be attacked are the ones in the brain's memory center. "When we treated brain tissue from mice suffering from Alzheimer's disease with vitamin C, we could see that the toxic protein aggregates were dissolved. Our results show a previously unknown model for how vitamin C affects the amyloid plaques," says Dr. Katrin Mani, reader in Molecular Medicine at Lund University. "Another interesting finding is that the useful vitamin C does not need to come from fresh fruit. In our experiments, we show that the vitamin C can also be absorbed in larger quantities in the form of dehydroascorbic acid from juice that has been kept overnight in a refrigerator, for example." There is at present no treatment that cures Alzheimer's disease, but the research is aimed at treatments and methods to delay and alleviate the progression of the disease by addressing the symptoms. That antioxidants such as vitamin C have a protective effect against a number of diseases, from the common cold to heart attacks and dementia, has long been a focus of research. "The notion that vitamin C can have a positive effect on Alzheimer's disease is controversial, but our results open up new opportunities for research into Alzheimer's and the possibilities offered by vitamin C," says Dr. Mani.

July 22nd

Scientists Complete First Genome-Wide Mapping of 5hmC in Human Embryonic Stem Cells

Stem cell researchers at UCLA have generated the first genome-wide mapping of a DNA modification called 5-hydroxymethylcytosine (5hmC) in embryonic stem cells, and discovered that it is predominantly found in genes that are turned on, or active. The finding by researchers with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA may prove to be important in controlling diseases like cancer, where the regulation of certain genes plays a role in disease development. "Any way you can control genes will be hugely important for human disease and cancer," said Dr. Steven E. Jacobsen, a professor of molecular, cell and developmental biology in the Life Sciences and a Howard Hughes Medical Institute investigator. "Cancer is generally a problem of genes being inappropriately turned off or mutated, like tumor suppressors genes, or genes that should be off getting switched on." The study appears in the July issue of the journal Genome Biology. 5hmC is formed from the DNA base cytosine by adding a methyl group and then a hydroxy group. The molecule is important in epigenetics - the study of changes in gene expression caused by mechanisms other than changes in the DNA sequence - because the newly formed hydroxymethyl group on the cytosine can potentially switch a gene on and off, Dr. Jacobsen said. The molecule 5hmC was only recently discovered, and its function has not been clearly understood, Dr. Jacobsen said. Until now, researchers didn't know where 5hmC was located within the genome. "That is important to know because it helps you to understand how it is functioning and what it's being used for," said Dr. Jacobsen, who also is a researcher with UCLA's Jonsson Comprehensive Cancer Center.

Genes of Endangered River Turtle Reveal Ancient Influence of Maya Indians

A genetic study focusing on the Central American river turtle (Dermatemys mawii) recently turned up surprising results for a team of Smithsonian scientists involved in the conservation of this critically endangered species. Small tissue samples collected from 238 wild turtles at 15 different locations across their range in Southern Mexico, Belize, and Guatemala revealed a "surprising lack" of genetic structure, the scientists write in a paper published online on May 17, 2011, in the journal Conservation Genetics. The turtles, which are entirely aquatic, represent populations from three different river basins that are geographically isolated by significant distance and high mountain chains. "We were expecting to find a different genetic lineage in each drainage basin," explains the paper's main author Dr. Gracia González-Porter of the Center for Conservation and Evolutionary Genetics at the Smithsonian Conservation Biology Institute. "Instead, we found the mixing of lineages. It was all over the place." Despite appearing isolated, the genetic data showed the different turtle populations had been in close contact for years. "But how?" the researchers wondered. The best possible explanation, Dr. González-Porter and her colleagues say, is that for centuries humans have been bringing the turtles together. The turtles have been used as food, in trade, and in rituals for millennia, widely transported and customarily kept in holding ponds until they were needed. “For centuries, this species has been part of the diet of the Mayans and other indigenous people who lived in its historic distribution range," the scientists point out in their paper. "D.