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Archive - Oct 2015

October 8th

First Ancient African Human Genome Sequenced; Profound Influence of Mysterious “Eurasian Backflow” into Horn of Africa Revealed by Comparison of Ancient “Mota Man” Genome with DNA of Modern Africans

The first ancient human genome from Africa to be sequenced has revealed that a wave of migration back into Africa from Western Eurasia approximately 3,000 years ago was up to twice as significant as previously thought, and affected the genetic make-up of populations across the entire African continent. The genome that was sequenced was recovered from the skull of a man buried face-down 4,500 years ago in a cave called Mota (image) in the highlands of Ethiopia, a cave cool and dry enough to preserve his DNA for thousands of years. Previously, ancient genome analysis has been limited to samples from northern and arctic regions. The latest study is the first time an ancient human genome has been recovered and sequenced from Africa, the source of all human genetic diversity. The findings were published online on October 8, 2015 in Science. The article is titled “Ancient Ethiopian Genome Reveals Extensive Eurasian Admixture throughout the African Continent.” The ancient genome predates a mysterious migratory event that took place roughly 3,000 years ago, and is known as the “Eurasian backflow,” when people from regions of Western Eurasia such as the Near East and Anatolia suddenly flooded back into the Horn of Africa. The ancient genome enabled researchers to run a millennia-spanning genetic comparison and determine that these Western Eurasians were closely related to the Early Neolithic farmers who had brought agriculture to Europe 4,000 years earlier. By comparing the ancient African genome to DNA from modern Africans, the team has been able to show that, not only do East African populations today have as much as 25% Eurasian ancestry from this “backflow” event, but that African populations in all corners of the continent - from the far West to the South - have at least 5% of their genome traceable to the Eurasian migration.

Georgetown’s Experimental Ewing Sarcoma & Prostate Cancer Drug Turns Off Mutant Cancer Gene in Animals with Leukemia

A compound discovered and developed by a team of Georgetown Lombardi Comprehensive Cancer Center researchers that halts cancer in animals with Ewing sarcoma and prostate cancer appears to work against some forms of leukemia, too. The team's latest work, with Austrian colleagues and including this leukemia finding, was published online on October 8, 2015 in an open-access article in Oncotarget. The compound is YK-4-279, the first drug targeted at similar chromosomal translocations found in Ewing sarcoma, prostate cancer, and in some forms of leukemia. Translocations occur when two normal genes break off from a chromosome and fuse together in a new location. This fusion can produce new genes that code for proteins, which can then push cancer cells to become more aggressive and spread. One of those proteins is EWS-FLI1. YK-4-279 appears effective in controlling the cancer promoting functions of EWS-FLI1. The Oncotarget article is titled “YK-4-279 Effectively Antagonizes EWS-FLI1 Induced Leukemia in a Transgenic Mouse Model.” "EWS-FLI1 is already known to drive a rare, but deadly, bone cancer called Ewing sarcoma, which occurs predominantly in children, teens, and young adults," says Aykut Üren (photo), M.D., Professor of Molecular Oncology at Georgetown Lombardi. "It also appears to drive cancer cell growth in some prostate cancers." In this new study led by Dr. Üren and colleagues, mice with EWS-FLI1-driven leukemia were given injections of YK-4-279 five days per week for two weeks and compared with untreated mice. By the end of the first week, the mice receiving YK-4-279 had much lower numbers of leukemia cells.

Cancer Rare in Elephants: 38 Extra Copies of p53 Tumor Suppressor Gene May Be Why

Why elephants rarely get cancer is a mystery that has stumped scientists for decades. Now, a study led by researchers at Huntsman Cancer Institute (HCI) at the University of Utah and Arizona State University, and including researchers from the Ringling Bros. Center for Elephant Conservation, may have found the answer. According to the results, published online on October 8, 2015 in an open-access article in the Journal of the American Medical Association (JAMA), and determined over the course of several years and in a unique collaboration between HCI, Primary Children's Hospital, Utah's Hogle Zoo, and the Ringling Bros. Center for Elephant Conservation, elephants have 38 additional modified copies of a gene that encodes p53, a well-defined tumor suppressor, as compared to humans, who have only two. Further, elephants may have a more robust mechanism for killing damaged cells that are at risk for becoming cancerous. In isolated elephant cells, this activity is doubled compared to healthy human cells, and five times that of cells from patients with Li-Fraumeni Syndrome, who have only one working copy of p53 and more than a 90 percent lifetime cancer risk in children and adults. The results suggest extra p53 could explain elephants' enhanced resistance to cancer. The JAMA article is titled “Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.” An JAMA open-access editorial accompanies the research report (see links to both articles below)."Nature has already figured out how to prevent cancer.

October 8th

Common Gene Variant Linked to Aneuploidy & Early Pregnancy Loss; Variant Present in 50% of Women; Scientists Suggest Low Fertility May Have Been Advantageous to Long-Term Male-Female Bonding; Findings Reported at ASHG 2015 Annual Meeting

Researchers have identified a common genetic variant strongly associated with chromosome gains and losses during the early stages of human embryonic development. These errors in cell division, which are almost always fatal to the embryo, are thought to be a major cause of early pregnancy loss in humans and contribute to failure of in vitro fertilization (IVF) treatments. The findings were presented on Thursday, October 8, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore, Maryland. Healthy human somatic cells contain 23 pairs of chromosomes, for a total of 46. However, errors during the cell replication process can cause the chromosomes to distribute unevenly, a condition known as aneuploidy. “Early in human development, this process is particularly error-prone, affecting as many as 75 percent of embryos and often causing pregnancy loss as soon as five days after fertilization – before the mother even knows she is pregnant,” explained Rajiv McCoy, Ph.D., a postdoctoral researcher at the University of Washington and first author on the study. The title of the presented abstract is “Complex Mitotic-Origin Aneuploidy in Human Embryos: Genetic Risk Factors and Fertility Consequences.” Previous research has found a correlation between the age of the mother (but not the father) and the likelihood of aneuploidy. In fact, it is the mother’s genes that govern cell replication during the first few days of embryonic development. “However,” Dr. McCoy said, “this relationship did not fully account for the variation in aneuploidy we found within each maternal age group, so we guessed a genetic factor was also involved.” Using data collected by collaborators at Natera, Inc., Dr.

Male Sexual Orientation Accurately Predicted by Model Using Epigenetic Markers and New Algorithm; Study Analyzes DNA-Methylation Patterns in Pairs of Identical Male Twins; Results Presented at American Society of Human Genetics (ASHG) 2015 Annual Meeting

An algorithm using epigenetic information from just nine regions of the human genome can predict the sexual orientation of males with up to 70 percent accuracy, according to research presented on Thursday, October 8, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting in Baltimore, Maryland. “To our knowledge, this is the first example of a predictive model for sexual orientation based on molecular markers,” said Tuck C. Ngun, Ph.D., first author on the study and a postdoctoral researcher at the David Geffen School of Medicine of the University of California, Los Angeles (UCLA). The title of Dr. Ngun’s ASHG abstract is “A Novel Predictive Model of Sexual Orientation Using Epigenetic Markers.” Beyond the genetic information contained in DNA, the researchers examined patterns of DNA methylation – a molecular modification to DNA that affects when and how strongly a gene is expressed – across the genome in pairs of identical male twins. While identical twins have exactly the same genetic sequence, environmental factors lead to differences in how their DNA is methylated. Thus, by studying twins, the researchers could control for genetic differences and tease out the effect of methylation. In all, the study involved 37 pairs of twins in which one twin was homosexual and the other was heterosexual, and 10 pairs in which both twins were homosexual. “A challenge was that because we studied twins, their DNA methylation patterns were highly correlated,” Dr. Ngun explained. Even after some initial analysis, the researchers were left with over 400,000 data points to sort through.

Smoking and Heavy Alcohol Use Associated with Epigenetic Signs (DNA Methylation Patterns) of Acclerated Aging; Moderate Drinking Associated with Healthiest Aging; Results Presented at American Society of Human Genetics (ASHG) 2015 Annual Meeting

Cigarette smoking and heavy alcohol use cause epigenetic changes to DNA that reflect accelerated biological aging in distinct, measurable ways, according to research presented on Thursday, October 8, at the American Society of Human Genetics (ASHG) 2015 Annual Meeting n Baltimore, Maryland. Using data from the publicly available Gene Expression Omnibus (, Robert A. Philibert, M.D., Ph.D., and colleagues at the University of Iowa, and other institutions, analyzed patterns of DNA methylation, a molecular modification to DNA that affects when and how strongly a gene is expressed. Prior research had shown that methylation patterns change in predictable ways as people age, as well as in response to environmental exposures, such as cigarette smoke and alcohol. In these earlier studies, Dr. Philibert’s laboratory identified two specific locations in the genome, base pairs cg05575921 on the AHRR gene and cg23193759 on chromosome 10, at which methylation levels were highly associated with smoking and alcohol consumption, respectively. In fact, they showed, DNA methylation levels at these two locations were a better measure of substance use than people’s self-reported estimates. Thus, in this follow-up study, described at the ASHG meeting in a presentation delivered by Meeshanthini Dogan (photo), M.S.,on Thursday, October 8, Ms. Dogan and Dr. Philibert used methylation levels as a proxy for tobacco and alcohol consumption. They estimated each person’s biological age using a previously validated epigenetic “clock” based on methylation levels at 71 locations in the genome, as measured by the widely used Infinium HumanMethylation450 BeadChip Kit from Illumina (

Students Generate Useful Information on Immune System & Nervous System Responses of Sea Star to Devastating Wasting Disease Caused by Densovirus; Analyze Expression of 30,000 Genes in Sick and Healthy Sea Stars

Though millions of sea stars along the West Coast have perished in the past several years from an apparent wasting disease, scientists still don't know why. The iconic marine creature develops white lesions on its limbs and within days can dissolve or "melt" into a gooey mass. Last year, researchers identified a type of pathogen known as a densovirus as the likely cause, but they still can't explain the mass die-off three years ago or why a common ocean virus can wreak havoc on so many starfish species from Alaska to Southern California. Now, a group of young marine-disease researchers from around the country has contributed key information about the sea stars' immune response when infected with this virus. The students, while taking a summer class at the University of Washington's (UW’s) Friday Harbor Laboratories, looked specifically at how genes expressed themselves in both healthy and sick sea stars. It's the first time researchers have tracked how the genes behave when encountering this naturally occurring pathogen (densovirus), which could help explain how sea stars attempt to fight the virus and why they develop lesions and appear to melt. The researchers published their findings in the open-access journal PLOS ONE in July 15, 2015. The article is titled “Up in Arms: Immune and Nervous System Response to Sea Star Wasting Disease.” "Doing this study isn't going to save the sea stars, but, from an ecological perspective, it provides new information," said Steven Roberts, Ph.D., a UW associate professor of aquatic and fishery sciences. "This could be a building block for future studies on the evolution of immune repertoires." Dr.

DNA-Based Beacon for Single-Step Fluorescence Detection of Diagnostic Antibodies in Diseases Such As Rheumatoid Arthritis and HIV; Flexible, Modular Nano “Machine” Offers Faster, Cheaper Alternative to Current Approaches

New research may revolutionize the slow, cumbersome, and expensive process of detecting the antibodies that can help with the diagnosis of infectious and auto-immune diseases such as rheumatoid arthritis and HIV. An international team of researchers has designed and synthetized a nanometer-scale DNA "machine" whose customized modifications enable it to recognize a specific target antibody. The researchers’ new approach, which they described online on September 4, 2015 in Angewandte Chemie, promises to support the development of rapid, low-cost antibody detection at the point-of-care, eliminating the the treatment initiation delays and the increasing healthcare costs associated with current techniques. The article is titled “A Modular, DNA-Based Beacon for Single-Step Fluorescence Detection of Antibodies and Other Proteins.” The binding of the antibody to the DNA machine causes a structural change (or switch), which generates a light signal. The sensor does not need to be chemically activated and is rapid (acting within five minutes), enabling the targeted antibodies to be easily detected, even in complex clinical samples such as blood serum. In the abstract of their article, the scientists technically describe their new system as follows. The scientists say they have developed “a versatile platform for the one-step fluorescence detection of both monovalent and multivalent proteins. This system is based on a conformation-switching stem–loop DNA scaffold that presents a small-molecule, polypeptide, or nucleic-acid recognition element, on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair.

Singapore, Duke Scientists Identify Genes Underlying Distinct Group of Breast Tumors: Fibroepithelial Tumors, Benign & Malignant Forms

A team from the SingHealth Duke-NUS Academic Medical Centre, comprising scientists and clinicians from the National Cancer Centre Singapore (NCCS), Singapore General Hospital (SGH), and Duke-NUS Graduate Medical School, has uncovered the genetic landscape of a distinct breast tumor group called fibroepithelial tumors. Their study identified the culprit genes behind the formation and progression of these tumors, potentially improving the accuracy of breast cancer diagnosis and enhancing clinical intervention for patients with such tumors. The study's findings were published online on October 5, 2015 in Nature Genetics. The article is titled “Genomic Landscapes of Breast Fibroepithelial Tumors.” Fibroepithelial tumors are a distinct breast tumor group which includes two tumor types - fibroadenomas and phyllodes tumors. Fibroadenomas are the most common benign breast tumors in women of reproductive age, with thousands of women in Singapore and millions worldwide estimated to be diagnosed with fibroadenomas every year. Only last year, the team identified novel MED12 mutations in the majority of fibroadenomas, a finding that was also reported in Nature Genetics and has since attracted attention and interest worldwide. Now, they have charted the genetic landscape for fibroadenomas, as well as phyllodes tumors, another subtype of fibroepithelial tumors that have both benign and cancerous forms, the latter accounting for about two per cent of breast cancers in Singapore. "Breast cancer is the leading cancer affecting women in Singapore.

October 7th

Stem-Cell-Derived Cone Cells Growing to Confluence Form Organized Retinal Tissue 150 Microns Thick; Never Achieved Before; Might Enable Transplants to Treat Age-Related Macular Degeneration (ARMD)

Age-related macular degeneration (ARMD) could be treated by transplanting photoreceptors produced by the directed differentiation of stem cells, thanks to findings published online on October 6, 2015 in the journal Development by Professor Gilbert Bernier of the University of Montreal and its affiliated Maisonneuve-Rosemont Hospital, together with colleagues. The article is titled “Differentiation of Human Embryonic Stem Cells into Cone Photoreceptors through Simultaneous Inhibition of BMP, TGFβ, and Wnt Signaling.” Dr. Bernier is Director of the Stem Cell and Developmental Biology Laboratory at Maisonneuve-Rosemont Hospital and a Professor with the Department of Neuroscience and the Department of Opthalmology at the University of Montreal. ARMD is a common eye problem caused by the loss of cone cells. Dr. Bernier's team has developed a highly effective in vitro technique for producing light-sensitive retina cells from human embryonic stem cells. "Our method has the capacity to differentiate 80% of the stem cells into pure cones," Dr. Gilbert explained. "Within 45 days, the cones that we allowed to grow towards confluence spontaneously formed organized retinal tissue that was 150 microns thick. This has never been achieved before." In order to verify the technique, Dr. Bernier injected clusters of retinal cells into the eyes of healthy mice. The transplanted photoreceptors migrated naturally within the retina of their host. "Cone transplant represents a therapeutic solution for retinal pathologies caused by the degeneration of photoreceptor cells," Dr. Bernier explained.