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Archive - May 2015

May 5th

Single-Base Change in Promoter Region of HTT Gene Can Significantly Alter Age of Onset in Huntington’s Disease

Researchers at Sweden’s Karolinska Institutet and at the University of British Columbia, Canada, have identified a gene variant in the promoter region of the gene for the “huntingtin” (HTT) protein that influences whether Huntington’s disease develops earlier or later than expected. The findings, which were published online on May 4, 2015 in Nature Neuroscience, can contribute to improved diagnosis and disease-modifying therapies. The title of the article is “A SNP in the HTT Promoter Alters NF-kB Binding and Is a Bidirectional Genetic Modifier of Huntington Disease.” A typical symptom of the inherited, progressive, neurodegenerative Huntington’s disease is involuntary movements. While the symptom normally debuts in middle-age, there is wide individual variation in how the disease manifests itself, and even though two people carry the exact same genetic mutation that codes for the mutated HTT protein, there can be up to a 20-year difference in disease onset. Scientists have now discovered a single-base change in the promoter region of the HTT gene and they think this minor change plays an important role in the variation in disease onset. “We’ve identified, for the first time, a gene variant that affects the onset of the disease,” says lead author Dr. Kristina Bečanović (photo) from Karolinska Institutet’s Department of Clinical Neuroscience. “What’s interesting is that we managed to show that it can both delay and accelerate the development of the disease, depending on which gene copy it sits on.” Most people who develop Huntington’s disease have one normal and one mutated huntingtin gene residing on two homologous chromosomes.

How a Retrotransposon Find Its Target in the Genome

To understand how transposable elements shape genomes, where they are maintained over generations, it is vital to discover the mechanisms behind their targeted integration. Researchers from the Laboratoire Pathologie et Virologie Moléculaire (CNRS/Inserm/Université Paris Diderot), in collaboration with researchers from CEA3 and a laboratory at the University of Minnesota, have identified an interaction between two proteins that is essential for the integration of a transposable element into a specific area of the yeast genome. These results, published in the May 1, 2015 issue of Science, emphasize the role of these mobile DNA sequences in the evolution and adaptation of organisms, and their potential value for gene therapy. The article is titled “An RNA Polymerase III Subunit Determines Sites of Retrotransposon Integration.” Transposable elements are DNA sequences capable of moving within genomes. They represent a significant proportion of the genome and play an important role in its evolution. By integrating into the DNA, these transposable elements can contribute to genome plasticity and the emergence of new cellular functions. Conversely, they can also cause mutations that endanger cell survival. Their integration usually occurs in specific gene-poor regions, where such integration is least harmful. The mechanisms that make this targeted integration possible are still poorly understood. The authors of the current study focused on the Ty1 retrotransposon5 of the yeast Saccharomyces cerevisiae to examine how the integration site is determined. A retrotransposon is a particular type of transposable element, capable of replicating itself in a "copy and paste"-like method. It is thus able to multiply and invade a genome. This replication involves an RNA intermediate.

First Extensive Description of the Human Secreted miRNome Published; Results Call into Question Current Utility of miRNAs As Blood Sample Biomarkers for Early Stages of Cancer

In an elaborate study, biologists from the University of Luxembourg have determined that microRNAs are, contray to many hopes, not yet suitable for early diagnosis of skin cancer, as well as supposedly for other types of cancer, in blood samples. For the first time, these scientists analyzed all microRNAs in the serum of healthy people and thus provided a first complete image of the human “miRNome“ in blood samples. The researchers were even explicitly complimented by their reviewers for the rigorous work – a rare occasion. The article was published online on March 26, 2015 in an open-access article in Oncotarget. The article is titled “Comparison of a Healthy miRNome with Melanoma Patient miRNomes: Are microRNAs Suitable Serum Biomarkers for Cancer?” In order to detect cancer early, researchers all around the globe are seeking to identify molecules that might point to the emergence of a disease in blood samples early on. Promising among these so-called biomarkers are microRNAs, molecules that act as universal switches inside the body. According to Dr. Stephanie Kreis, Principal Lecturer of the research group “Signal Transduction” of the Life Sciences Research Unit at the University of Luxembourg, “microRNAs might be exceptional markers, because they are very stable and hence easily traceable, as well as tissue-specific.” In tissue samples, these “molecule snippets” can indeed act as a measure for early recognition of cancer - but is this also applicable to the more feasible and accessible blood sample?

May 4th

Two Genes Newly Associated with Familial Pulmonary Fibrosis

Researchers at the University of Texas (UT) Southwestern Medical Center have identified mutations in two genes that cause a fatal lung-scarring disease known as familial pulmonary fibrosis. Researchers also determined that these mutations cause excessive shortening of telomeres. Telomeres are repetitive sequences of DNA that protect the ends of chromosomes from deteriorating. Telomeres are sometimes compared to the plastic ends of shoelaces, which protect shoelaces from fraying. Together, the two mutated genes − PARN and RTEL1 − explain about seven percent of familial pulmonary fibrosis and strengthen the link between lung fibrosis and telomere dysfunction, according to the study, which was done in conjunction with the Yale Center for Genome Analysis, and is published in the May 2015 issue of Nature Genetics. The article is titled “Exome Sequencing Links Mutations in PARN and RTEL1 with Familial Pulmonary Fibrosis and Telomere Shortening.” “Although RTEL1 had been previously linked to telomere biology, our finding that PARN was involved in telomere regulation and human disease was completely unexpected,” said senior author Dr. Christine Kim Garcia (photo), M.D., Ph.D., Associate Professor of Internal Medicine and with the Eugene McDermott Center for Human Growth and Development. Approximately 50,000 people in the United States annually develop idiopathic pulmonary fibrosis, a progressive disease that principally affects the elderly, according to the Pulmonary Fibrosis Foundation. Approximately one in 20 people have a close relative with the disease, in which case they themselves are considered to possibly have familial pulmonary fibrosis. Without a lung transplant, pulmonary fibrosis patients typically die within three years of diagnosis.

May 2nd

Low Sunlight (Implicating Vitamin D Deficiency) Linked to Higher Risk of Pancreatic Cancer in 172-Country Study

In an article published online on April 9, 2015 in the Journal of Steroid Biochemistry and Molecular Biology, researchers at the University of California San Diego (UC San Diego) School of Medicine report that pancreatic cancer rates are highest in countries with the least amount of sunlight. Low sunlight levels were due to a combination of heavy cloud cover and high latitude. The article is titled “Cloud Cover-Adjusted Ultraviolet B Irradiance and Pancreatic Cancer Incidence in 172 Countries.” "If you're living at a high latitude or in a place with a lot of heavy cloud cover, you can't make vitamin D most of the year, which results in a higher-than-normal risk of getting pancreatic cancer," said first author Cedric F. Garland, DPH, Adjunct Professor in the Department of Family Medicine and Public Health and member of UC San Diego Moores Cancer Center. "People who live in sunny countries near the equator have only one-sixth of the age-adjusted incidence rate of pancreatic cancer as those who live far from it. The importance of sunlight deficiency strongly suggests - but does not prove - that vitamin D deficiency may contribute to risk of pancreatic cancer." Limited foods naturally contain vitamin D. Fatty fish, such as salmon and tuna, are good sources; beef liver, cheese, and egg yolks provide small amounts. Vitamin D is often added as a fortifying nutrient to milk, cereals, and juices, but experts say most people also require additional vitamin D to be produce by the body when skin is directly exposed to sunlight, specifically, ultraviolet B radiation. Skin exposed to sunshine indoors through a window will not produce vitamin D. Cloudy skies, shade, and dark-colored skin also reduce vitamin D production. The UC San Diego team, led by Dr. Garland and Edward D.