The most likely wild chicken ancestor, photographed in India.

More than 10,000 years ago, our ancestors began to expand their organization offood productionpurposefully promoting certain plants and animals they found tasty or useful. Over time, they domesticated those species, inserting human preferences into the process of natural selection.

We know today that agriculture and domesticated species arose separately in different regions around the world. Grains, beans, and livestock appear to be some of the earliest species domesticated in Southwest Asia, for example. But many questions remain about why humans shifted from hunting and gathering to agriculture and how the process of domesticatingspecies unfoldeda process that, in cases like wheat and rice, appears to have taken more than a thousand years.

A special section in this weeks Proceedings of the National Academy of Sciencesdelvedinto what science has discovered about domestication and how toprovide answers to ourremaining questions about the lives of prehistoric people and their relationship with the plants and animals around them.

In one of the examples explored inPNAS, scientists turned to chickens in their search for answers to an age old question.

It's not the questionyoure probably thinking of. The jurys still out on which came first, as well as motivations for road crossing. Instead, scientists were looking to see if certain traits commonly found in modern chickenswere the same traits selected for whenancient humans beganthe domestication process.

To study the origins of these traits, the scientists compared the DNA in modern chickens to samples obtainedfrom archeological sites ranging from 200 years BC to the 18th century.

In chickens, traits that are considered hallmarks of domestication include yellow skin. This iscommonly found in most modern breeds, and it is caused by a recessive allele inthe gene that breaks down orange-yellow compounds known as carotenoids. However, its absent in the chicken's primary ancestor, the Red Jungle Fowl, which still lives in Asia and looks a lot like a chicken. Another key trait associated with domestication is a mutation in a thyroid hormone receptorthe jungle fowl lacks it, but almost all modern chicken breeds have it.

In the past, many researchers concluded that these traits must have been selected long ago by our ancestors as they first domesticated chickens. But the in-depth genetic analysis showed that they onlybecame common in chicken breeds relatively recentlywithin the past couple hundred years.

The significance here goes far beyond chicken genetics. Its so tempting to trust neat little evolutionary storiesall the chickens have the same hormonal mutation, that must have been one of the things our ancestors selected for long, long agowhen it very well might be random chance. The genetic process of domestication cant just be assumed from modern data.

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Reading human history using ancient chicken DNA and chili peppers

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Newswise (NEW YORK April 24) A substantial proportion of risk for developing autism spectrum disorders (ASD), resides in genes that are part of specific, interconnected biological pathways, according to researchers from the Icahn School of Medicine at Mount Sinai, who conducted a broad study of almost 2,500 families in the United States and throughout the world. The study, titled Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders, was first published online in The American Journal of Human Genetics on April 24.

ASD affects about one percent of the population in the United States and is characterized by impairments in social interaction and communication, as well as by repetitive and restricted behaviors. ASD ranges from mild to severe levels of impairment, with cognitive function among individuals from above average to intellectual disability.

Previously, ASD has been shown to be highly inheritable, and genomic studies have revealed that that there are various sources of risk for ASD, including large abnormalities in whole chromosomes, deletions or duplications in sections of DNA called copy number variants (CNVs), and even changes of single nucleotides (SNVs) within a gene; genes contain instructions to produce proteins that have various functions in the cell.

The researchers reported numerous CNVs affecting genes, and found that these genes are part of similar cellular pathways involved in brain development, synapse function and chromatin regulation. Individuals with ASD carried more of these CNVs than individuals in the control group, and some of them were inherited while others were only present in offspring with ASD.

An earlier study, results of which were first published in 2010, highlighted a subset of these findings within a cohort of approximately 1,000 families in the U.S. and Europe; this larger study has expanded that cohort to nearly 2,500 families, each comprising trios of two parents and one child. By further aggregating CNVs and SNVs (the latter identified in other studies), Mount Sinai researchers discovered many additional genes and pathways involved in ASD.

We hope that these new findings will help group individuals with ASD based upon their genetic causes and lead to earlier diagnosis, and smarter, more focused therapies and interventions for autism spectrum disorders, said first author Dalila Pinto, PhD, Assistant Professor of Psychiatry, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai. Dr. Pinto is a Seaver Foundation Faculty Fellow, and a member of the Mindich Child Health & Development Institute, the Icahn Institute for Genomics and Multiscale Biology, and the Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai; other Mount Sinai researchers on this study include Mafalda Barbosa, Graduate Student in Psychiatry; Xiao Xu, PhD, Postdoctoral Fellow in Psychiatry; Alexander Kolevzon, MD, Clinical Director of the Seaver Autism Center and Associate Professor of Psychiatry and Pediatrics; and Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center, Vice Chair for Research in Psychiatry, and Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences.

This study was jointly supported through the main funders of the International Autism Genome Project: Autism Speaks, the Health Research Board (Ireland), the Hillbrand Foundations, the Genome Canada, the Ontario Genomics Institute, and the Canadian Institutes of Health Research.

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Mount Sinai Researchers Identify Genetic Alterations in Shared Biological Pathways as Major Risk Factor for Autism ...

Women Shaping a Better Tomorrow: Penn Association of Alumnae 100th Anniversary Colloquium
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Contact: Glenna Picton picton@bcm.edu 713-798-4710 Baylor College of Medicine

HOUSTON (April 24, 2014) A team of international scientists led by Baylor College of Medicine has discovered a novel gene (CLP1) associated with a neurological disorder affecting both the peripheral and central nervous systems. Together with scientists in Vienna they show that disturbance of a very basic biological process, tRNA biogenesis, can result in cell death of neural progenitor cells. This leads to abnormal brain development and a small head circumference as well as dysfunction of peripheral nerves.

The study published today in the current issue of the journal Cell.

"This is the first human disorder associated with the gene CLP1," said Dr. Ender Karaca, post-doctoral associate in the department of molecular and human genetics at Baylor.

The gene find is significant because CLP1 has a role in RNA processing and has important implications for genomic approaches to Mendelian disease and for our understanding of human biology and brain development, Karaca said.

Karaca's work with families of this rare disorder began many years ago during his residency training as a clinical geneticist in Turkey.

A chance meeting with Dr. James R. Lupski, the Cullen Professor and Vice Chair of Molecular and Human Genetics and professor of pediatrics at Baylor, at a medical meeting in Istanbul, Turkey would lead to Karaca's recruitment as a trainee in Lupski's lab where the research took off and eventually the team unveiled new clues about the genetic malfunction that may be causing the disorder in these families.

Lupski leads the Center for Mendelian Genomics at Baylor, a joint program with the Johns Hopkins University School of Medicine that is funded by the National Human Genome Research Institute. The Center is focused on advancing research of the cause of rare, single-gene diseases usually called Mendelian disorders.

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Newswise (SALT LAKE CITY)A computational tool developed at the University of Utah (U of U) has successfully identified diseases with unknown gene mutations in three separate cases, U of U researchers and their colleagues report in a new study in The American Journal of Human Genetics. The software, Phevor (Phenotype Driven Variant Ontological Re-ranking tool), identifies undiagnosed illnesses and unknown gene mutations by analyzing the exomes, or areas of DNA where proteins that code for genes are made, in individual patients and small families.

Sequencing the genomes of individuals or small families often produces false predictions of mutations that cause diseases. But the study, conducted through the new USTAR Center for Genetic Discovery at the U of U, shows that Phevors unique approach allows it to identify disease-causing genes more precisely than other computational tools.

Mark Yandell, Ph.D, professor of human genetics, led the research. He was joined by co-authors Martin Reese, Ph.D., of Omicia Inc., an Oakland, Calif., genome interpretation software company, Stephen L. Guthery, M.D., professor of pediatrics who saw two of the cases in clinic, a colleague at the MD Anderson Cancer Center in Houston, and other U of U researchers. Marc V. Singleton, a doctoral student in Yandells lab, is the first author.

Phevor represents a major advance in personalized health care, according to Lynn B. Jorde, Ph.D., U of U professor and chair of human genetics and also a co-author on the study. As the cost of genome sequencing continues to drop, Jorde expects it to become part of standardized health care within a few years, making diagnostic tools such as Phevor more readily available to clinicians.

With Phevor, just having the DNA sequence will enable clinicians to identify rare and undiagnosed diseases and disease-causing mutations, Jorde said. In some cases, theyll be able to make the diagnosis in their own offices.

Using Phevor in Clinic

Phevor works by using algorithms that combine the probabilities of gene mutations being involved in a disease with databases of phenotypes, or the physical manifestation of a disease, and information on gene functions. By combining those factors, Phevor identifies an undiagnosed disease or the most likely candidate gene mutation for causing a disease. It is particularly useful when clinicians want to identify an illness or gene mutation involving a single patient or the patient and two or three other family members, which is the most common clinical situation for undiagnosed diseases.

Yandell, the lead developer of the software, describes Phevor as the application of mathematics to biology. Phevor is a way to try to get the most out of a childs genome to identify diseases or find disease-causing gene mutations, Yandell said.

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Software Identifies Gene Mutations in 3 Undiagnosed Children

PUBLIC RELEASE DATE:

22-Apr-2014

Contact: Phil Sahm phil.sahm@hsc.utah.edu 801-581-2517 University of Utah Health Sciences

(SALT LAKE CITY)A computational tool developed at the University of Utah (U of U) has successfully identified diseases with unknown gene mutations in three separate cases, U of U researchers and their colleagues report in a new study in The American Journal of Human Genetics. The software, Phevor (Phenotype Driven Variant Ontological Re-ranking tool), identifies undiagnosed illnesses and unknown gene mutations by analyzing the exomes, or areas of DNA where proteins that code for genes are made, in individual patients and small families.

Sequencing the genomes of individuals or small families often produces false predictions of mutations that cause diseases. But the study, conducted through the new USTAR Center for Genetic Discovery at the U of U, shows that Phevor's unique approach allows it to identify disease-causing genes more precisely than other computational tools.

Mark Yandell, Ph.D, professor of human genetics, led the research. He was joined by co-authors Martin Reese, Ph.D., of Omicia Inc., an Oakland, Calif., genome interpretation software company, Stephen L. Guthery, M.D., professor of pediatrics who saw two of the cases in clinic, a colleague at the MD Anderson Cancer Center in Houston, and other U of U researchers. Marc V. Singleton, a doctoral student in Yandell's lab, is the first author.

Phevor represents a major advance in personalized health care, according to Lynn B. Jorde, Ph.D., U of U professor and chair of human genetics and also a co-author on the study. As the cost of genome sequencing continues to drop, Jorde expects it to become part of standardized health care within a few years, making diagnostic tools such as Phevor more readily available to clinicians.

"With Phevor, just having the DNA sequence will enable clinicians to identify rare and undiagnosed diseases and disease-causing mutations," Jorde said. "In some cases, they'll be able to make the diagnosis in their own offices."

Phevor works by using algorithms that combine the probabilities of gene mutations being involved in a disease with databases of phenotypes, or the physical manifestation of a disease, and information on gene functions. By combining those factors, Phevor identifies an undiagnosed disease or the most likely candidate gene mutation for causing a disease. It is particularly useful when clinicians want to identify an illness or gene mutation involving a single patient or the patient and two or three other family members, which is the most common clinical situation for undiagnosed diseases.

Yandell, the lead developer of the software, describes Phevor as the application of mathematics to biology. "Phevor is a way to try to get the most out of a child's genome to identify diseases or find disease-causing gene mutations," Yandell said.

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Applying math to biology: Software identifies disease-causing mutations in undiagnosed illnesses

Modern humanity's ancient cousins, the Neanderthals, lived in small groups that were isolated from one another, suggests an investigation into their DNA. The analysis also finds that Neanderthals lacked some human genes that are linked to our behavior. (Related: "Why Am I Neanderthal?")

In recent years, experts in ancient DNA have mapped out the genes of Neanderthals, a species of human that vanished some 30,000 years ago. These gene maps have revealed that many modern people share a small part of their ancestry, and a small percentage of their genes, with those early humans.

Now moving beyond ancestry, researchers are comparing these ancient gene maps to those of modern humans. The comparisons may point to genes that make us uniquely human and uncover links to the origins of genetic ailments.

Compared to Neanderthals, humanity appears to have evolved more when it comes to genes related to behavior, suggests a team headed by Svante Pbo, a pioneer in ancient genetics at Germany's Max Planck Institute for Evolutionary Anthropology. Their study was published today in the Proceedings of the National Academy of Sciences.

They note in particular that genes linked to hyperactivity and aggressive behavior in modern humans appear to be absent in Neanderthals. Also missing is DNA associated with syndromes such as autism.

"The paper describes some very interesting evolutionary dynamics," said paleoanthropologist John Hawks of the University of Wisconsin at Madison.

The Neanderthal genes suggest that sometime after one million to 500,000 years ago, Neanderthal numbers decreased and the population stayed small, Pbo's group determined. A small population size would have been bad news for Neanderthals, Hawks said, because it would have meant that "natural selection had less power to weed out bad mutations."

Ancient Answers

Pbo and colleagues looked at the genes of two ancient Neanderthals, one from Spain and one from Croatia. They compared the DNA of those individuals to that of a third Neanderthal who had lived in Siberia and whose DNA had been analyzed in an earlier study, and to the DNA of several modern humans.

"We find that [Neanderthals] had even less [genetic] variation than present-day humans," Pbo said by email. Genetic diversity among Neanderthals was about one-fourth as much as is seen among modern Africans, he said, and one-third that of modern Europeans or Asians.

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Neanderthals Lived in Small, Isolated Populations, Gene Analysis Shows

Human Genetics and Personalized Medicine, Dr. David Cox
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Image Caption: Scanning electron micrograph shows infectious spores produced by the deadly fungi Cryptococcus neoformans. Credit: Duke University

By Marla Vacek Broadfoot, Duke University

Ten-year effort yields map for finding weaknesses in the fungus

Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus neoformans a fungus responsible for a million cases of pneumonia and meningitis every year are so malleable and dangerous.

Now researchers have sequenced the entire genome and all the RNA products of the most important pathogenic lineage of Cryptococcus neoformans, a strain called H99. The results, which appear April 17 in PLOS Genetics, also describe a number of genetic changes that can occur after laboratory handling of H99 that make it more susceptible to stress, hamper its ability to sexually reproduce and render it less virulent.

The study provides a playbook that can be used to understand how the pathogen causes disease and develop methods to keep it from evolving into even deadlier strains.

We are beginning to get a grasp on what makes this organism tick. By having a carefully annotated genome of H99, we can investigate how this and similar organisms can change and mutate and begin to understand why they arent easily killed by antifungal medications, said study coauthor John Perfect, M.D., a professor of medicine at Duke who first isolated H99 from a patient with cryptococcal meningitis 36 years ago.

The fungus Cryptococcus neoformans is a major human pathogen that primarily infects individuals with compromised immune systems, such as patients undergoing transplant or those afflicted with HIV/AIDS. Researchers have spent many years conducting genetic, molecular and virulence studies on Cryptococcus neoformans, focusing almost exclusively on the H99 strain originally isolated at Duke. Interestingly, investigators have noticed that over time, the strain became less and less virulent as they grew it in the laboratory.

Virulence, or the ability of this organism to cause disease in mice or humans, is not very stable. It changes, and can rapidly be lost or gained. When the organism is in the host it is in one state, but when we take it out of the host and begin growing it in the laboratory it begins mutating, said Fred Dietrich, senior study author and associate professor of molecular genetics and microbiology at Duke University School of Medicine.

Dietrich and his colleagues decided that the best way to investigate how the virulence of this pathogen could change over time was to develop a carefully annotated genomic map of the H99 strain, both in its original state as well as after it had been cultured. In an effort that took ten years and dozens of collaborators, the researchers sequenced the original H99 and nine other cultured variants, analyzing both the genome, the genetic code written in the DNA, as well as the transcriptome, the RNA molecules that occupy the second step in the flow of genetic information from DNA to RNA to protein.

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Researchers Have Fully Sequenced The Deadly Human Pathogen Cryptococcus

Genomic Revolution: Catalina Lopez-Correa at TEDxHECMontreal
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When scientists first sequenced the genome of a Neanderthal, our extinct, heavy-browed human cousin, we learned a surprising amount about our own species too: many modern humans carry Neanderthal genes, proving we interbred with them long ago.

Now, researchers have offered the first glimpse of the Neanderthal epigenome, and once again their results offer tantalizing new theories about the modern human brain and skeleton.

While the findings are surprising, the fact that the Neanderthal epigenome holds important secrets should not be. In the past decade, scientists have discovered that epigenetics, the chemical signals that regulate how genes are expressed, are almost as important as genetics in understanding how organisms look and act.

By exploiting a trick of how ancient DNA degrades, an Israeli-led team of researchers has created a map of the Neanderthal epigenetic landscape and that of another extinct human species, the Denisovans. Their work, hailed as a fantastically exciting technical achievement, was published Thursday in the journal Science.

The most intriguing findings of the study are the clues that emerged when the researchers compared those archaic epigenetic maps to those of present-day humans.

More than 99 per cent of the ancient and modern maps were the same, which is what one would expect to find in closely-related human species that shared a common ancestor approximately 600,000 years ago.

But the maps were almost twice as likely to differ in regions associated with disease and, in a third of those cases, in regions associated with psychological and neurological diseases.

Scientists are a long way from being able to understand what this means, stressed Liran Carmel, who led the study along with Eran Meshorer and David Gokhman, all of the Hebrew University of Jerusalem.

But this raises the hypothesis that perhaps many genes in our brain have changed recently, specifically in our lineage, the lineage leading to Homo sapiens. And perhaps things like autism, schizophrenia and Alzheimers are side-effects of these very recent changes, said Carmel.

This is an interesting suggestion, that (brain disease) is a side-effect of us being Homo sapiens and having our unique cognitive capabilities.

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Neanderthal genetic landscape reveals key differences with humans

It's long been known that certain strains of human papillomavirus (HPV) cause cancer. Now, researchers at The Ohio State University have determined a new way that HPV might spark cancer development -- by disrupting the human DNA sequence with repeating loops when the virus is inserted into host-cell DNA as it replicates.

Worldwide, HPV causes about 610,000 cases of cancer annually, accounting for about five percent of all cancer cases and virtually all cases of cervical cancer. Yet, the mechanisms behind the process aren't yet completely understood.

This study, recently published in the journal Genome Research and reviewed in The Scientist, leveraged the massive computational power of the Ohio Supercomputer Center (OSC) systems. The researchers employed whole-genome sequencing, genomic alignment and other molecular analysis methods to examine ten cancer-cell lines and two head and neck tumor samples from patients -- each sequence comprising the three billion chemical units within the human genetic instruction set.

"Our sequencing data showed in vivid detail that HPV can damage host-cell genes and chromosomes at sites of viral insertion," said co-senior author David Symer, M.D., Ph.D., assistant professor of molecular virology, immunology and medical genetics at Ohio State's Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James).

"HPV can act like a tornado hitting the genome, disrupting and rearranging nearby host-cell genes," he said. "This can lead to overexpression of cancer-causing genes in some cases, or it can disrupt protective tumor-suppressor genes in others. Both kinds of damage likely promote the development of cancer."

The study's first author Keiko Akagi, Ph.D., a bioinformatics expert and research assistant professor of molecular virology, immunology and medical genetics at OSUCCC -- James, utilized the computational capabilities of OSC's HP-built Intel Xeon cluster. The 8,300+ cores of the Oakley Cluster offer Ohio researchers a total peak performance of 154 teraflops -- tech speak for making 154 trillion calculations per second -- and OSC's Mass Storage System provides them with more than 2 petabytes of storage.

"We observed fragments of the host-cell genome to be removed, rearranged or increased in number at sites of HPV insertion into the genome," said co-senior author Maura Gillison, M.D., Ph.D., professor of medicine, epidemiology and otolaryngology and the Jeg Coughlin Chair of Cancer Research at OSUCCC -- James. "These remarkable changes in host genes were accompanied by increases in the number of HPV copies in the host cell, thereby also increasing the expression of viral E6 and E7, the cancer-promoting genes."

Cancer-causing types of HPV produce two viral proteins, called E6 and E7, which are essential for the development of cancer, but are not alone sufficient to cause cancer. Additional alterations in host-cell genes are necessary for cancer to develop, which is where the destabilizing loops might play a significant role; genomic instability is a hallmark of human cancers, including the HPV virus.

"Our study reveals new and interesting information about what happens to HPV in the 'end game' in cancers," Symer says. "Overall, our results shed new light on the potentially critical, catastrophic steps in the progression from initial viral infection to development of an HPV-associated cancer."

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Newswise PHILADELPHIA - Daniel J. Rader, MD, a widely recognized international leader in the human genetics of lipoprotein biology and cardiovascular disease, has been named the new chair of the Department of Genetics in the Perelman School of Medicine at the University of Pennsylvania. He has been a faculty member at Penn for 20 years and is currently the chief of the Division of Translational Medicine and Human Genetics and the Edward S. Cooper, MD/Norman Roosevelt and Elizabeth Meriwether McLure Professor of Medicine.

As a prominent physician-scientist, Dr. Rader will bring his robust knowledge of genetic approaches to improving health to guide the department of Genetics into an era where genes play a role in our strategies to prevent and treat a broad array of diseases, said J. Larry Jameson, MD, PhD, Executive Vice President for the Health System and Dean of the Perelman School of Medicine. His long record of leadership in the classroom, the exam room, and the lab will be invaluable to the department and overall genetics research at Penn.

Dr. Rader holds multiple leadership roles at Penn Medicine. In addition to heading the Division of Translational Medicine and Human Genetics within the Department of Medicine, he also serves as Associate Director of the Institute for Translational Medicine and Therapeutics (ITMAT).

He co-directs the new Penn Medicine BioBank, an integrated, centralized resource for consenting, collecting, processing, and storing DNA, plasma/serum, and tissue for human genetics and translational research. This venture is a cornerstone of Penn Medicines efforts in human genetics and translational and personalized medicine. Dr. Rader also has key relationships with Penns Cardiovascular Institute (CVI) and Institute for Diabetes, Obesity, and Metabolism (IDOM).

In his research program, Dr. Rader has used human genetics and model systems to elucidate novel biological pathways in lipoprotein metabolism and atherosclerosis. His lab discovered and characterized the enzyme endothelial lipase, demonstrated its effects on high density lipoproteins (HDL) in mice, and then found that loss-of-function mutations in the gene cause high levels of HDL in humans. He is among the worlds leaders in using both humans and model systems to dissect the functional genomics of human genetic variants associated with plasma lipid traits as well as coronary heart disease.

He has had a long interest in Mendelian disorders of lipoprotein metabolism and has a strong translational interest in development of novel therapies for these disorders. He was involved in the identification of the molecular defect in a rare genetic disorder causing very low levels of low density lipoproteins (LDL), which spurred the development of inhibitors of this protein to reduce levels of LDL. Indeed, when one such drug was abandoned by a pharmaceutical firm, he went on to oversee its development for the orphan disease homozygous familial hypercholesterolemia (HoFH), characterized by extremely high levels of LDL and heart disease in childhood. This decade-long endeavor led to FDA and European approval of lomitapide, the first effective medication for the treatment of HoFH.

Dr. Rader has received numerous awards as a physician-scientist, including the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, the Bristol Myers Squibb Cardiovascular Research Award, the Doris Duke Charitable Foundation Distinguished Clinical Investigator Award, the Jeffrey M. Hoeg Award for Basic Science and Clinical Research from the American Heart Association, the American Heart Associations Clinical Research Prize, and the Clinical Research Forums Distinguished Clinical Research Award. He has been elected to the American Society of Clinical Investigation and to the Association of American Physicians. In 2011, he received one of the nations highest honors in biomedicine when he was elected to the Institute of Medicine.

Dr. Rader has also received many awards for his outstanding teaching activities. At the Perelman School of Medicine, he has received the William Osler Patient Oriented Research Award, as well as the Donald B. Martin Outstanding Teacher Award and the Outstanding Faculty Award from the Department of Medicine. Along with these accolades, Dr. Rader has been honored by Philadelphia magazine, which has named him to its Top Docs honor roll every year since 2002.

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Daniel J. Rader, MD, Named as Chair of the Department of Genetics at the Perelman School of Medicine at the University ...

When talking about genetic abnormalities at the DNA level that occur when chromosomes swap, delete or add parts, there is an evolving communication gap both in the science and medical worlds, leading to inconsistencies in clinical and research reports.

Now a study by researchers at Brigham and Women's Hospital (BWH) proposes a new classification system that may standardize how structural chromosomal rearrangements are described. Known as Next-Gen Cytogenetic Nomenclature, it is a major contribution to the classification system to potentially revolutionize how cytogeneticists worldwide translate and communicate chromosomal abnormalities. The study will be published online April 17, 2014 in The American Journal of Human Genetics.

"As scientists we are moving the field of cytogenetics forward in the clinical space," said Cynthia Morton, PhD, BWH director of Cytogenetics, senior study author. "We will be able to define chromosomal abnormalities and report them in a way that is integral to molecular methods entering clinical practice."

According to the researchers, advances in next-generation sequencing methods and results from BWH's Developmental Genome Anatomy Project (DGAP) revealed an assortment of genes disrupted and dysregulated in human development in over 100 cases. Given the wide variety of chromosomal abnormalities, the researchers recognized that more accurate and full descriptions of structural chromosomal rearrangements were needed.

The nomenclature proposed by Morton and her team goes beyond uncovering chromosomal abnormalities under a microscope to focusing on the unique molecules that are the building blocks of DNA -- nucleotides.

"Cytogeneticists compare karyograms, or pictures of chromosomes, to identify chromosomal abnormalities," said Morton. "In the current system available, we are able to describe certain characteristics of chromosomes, such as chromosome band levels. What we have developed is a new system for describing chromosomal abnormalities at a much more precise level."

"Currently, most DNA sequencing reports only provide nucleotide numbers of the breakpoints in various formats based on the reference genome sequence alignment," said Zehra Ordulu, MD, BWH Department of Obstetrics, Gynecology and Reproductive Medicine, lead study author. "But there are other important characteristics of the rearrangement -- including reference genome identification, chromosome band level, direction of the sequence, homology, repeats, and nontemplated sequence -- that are not described."

The proposed system addresses these characteristics and builds upon the International System for Human Cytogenetic Nomenclature, which is the current official classification system used to describe structural chromosome rearrangements.

To enable use and implementation of the proposed system, the researchers are developing an online tool called "BLA(S)T Output Sequence Tool of Nomenclature," or BOSToN. The tool works by aligning nucleotide sequences to reference human genome sequence. After processing the genetic information, the end result is the Next-Gen Cytogenetic Nomenclature that researchers and clinicians can then incorporate into their reports.

"BOSToN will reduce errors in sequence assessment and save time in generating nomenclature," according to Morton, "both of critical importance in the clinical setting."

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Refining language for chromosomes

PUBLIC RELEASE DATE:

17-Apr-2014

Contact: Marjorie Montemayor-Quellenberg mmontemayor-quellenberg@partners.org 617-525-6383 Brigham and Women's Hospital

Boston, MA When talking about genetic abnormalities at the DNA level that occur when chromosomes swap, delete or add parts, there is an evolving communication gap both in the science and medical worlds, leading to inconsistencies in clinical and research reports.

Now a study by researchers at Brigham and Women's Hospital (BWH) proposes a new classification system that may standardize how structural chromosomal rearrangements are described. Known as Next-Gen Cytogenetic Nomenclature, it is a major contribution to the classification system to potentially revolutionize how cytogeneticists worldwide translate and communicate chromosomal abnormalities. The study will be published online April 17, 2014 in The American Journal of Human Genetics.

"As scientists we are moving the field of cytogenetics forward in the clinical space," said Cynthia Morton, PhD, BWH director of Cytogenetics, senior study author. "We will be able to define chromosomal abnormalities and report them in a way that is integral to molecular methods entering clinical practice."

According to the researchers, advances in next-generation sequencing methods and results from BWH's Developmental Genome Anatomy Project (DGAP) revealed an assortment of genes disrupted and dysregulated in human development in over 100 cases. Given the wide variety of chromosomal abnormalities, the researchers recognized that more accurate and full descriptions of structural chromosomal rearrangements were needed.

The nomenclature proposed by Morton and her team goes beyond uncovering chromosomal abnormalities under a microscope to focusing on the unique molecules that are the building blocks of DNAnucleotides.

"Cytogeneticists compare karyograms, or pictures of chromosomes, to identify chromosomal abnormalities," said Morton. "In the current system available, we are able to describe certain characteristics of chromosomes, such as chromosome band levels. What we have developed is a new system for describing chromosomal abnormalities at a much more precise level."

"Currently, most DNA sequencing reports only provide nucleotide numbers of the breakpoints in various formats based on the reference genome sequence alignment," said Zehra Ordulu, MD, BWH Department of Obstetrics, Gynecology and Reproductive Medicine, lead study author. "But there are other important characteristics of the rearrangementincluding reference genome identification, chromosome band level, direction of the sequence, homology, repeats, and nontemplated sequencethat are not described."

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Refining the language for chromosomes

Dame Bridget Ogilvie: Women in Science
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Wellcome Trust Centre for Human Genetics
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Wellcome Trust Centre for Human Genetics - Video

Beings Less and Less Dependent on Parents to Exist Washington, D.C., April 10, 2014 (Zenit.org) Denise Hunnell, MD | 0 hits

Both the 1932 novel Brave New World by Aldous Huxley and the 1997 science fiction movie Gattaca are classified as dystopias because they depict societies riddled with misery, tragedy, and a dehumanizing culture. Both attribute this decline in civilization to manipulations of human genetics and perversions of human reproduction. In Brave New World the traditional family structure has completely disintegrated and children are manufactured in hatcheries through in vitro fertilization (IVF) and gestation. In Gattaca, human beings are enhanced through genetic alterations, and those who do not have their DNA modified are seen as second-class citizens.

It is curious that genetically modified humans can be clearly seen as dangerous and undesirable in fiction but are celebrated as great achievements in current biomedical sciences. In the name of progress we are steadily marching forward to separate human procreation from human relationships and make it a laboratory procedure.

The floodgates of artificial reproductive technology were opened in Great Britain on July 25, 1978, with the birth of Louise Brown, the first test tube baby. In the ensuing years the use of IVF has fueled the growth of the multi-billion dollar fertility industry. The growing demand for ova to produce children for infertile couples has led to the widespread exploitation of young women as egg donors. Similar exploitation of poor women in countries like India has occurred as couples seek both egg donors to help conceive a child and a surrogate mother to gestate the child. Both women and children are dehumanized as human reproduction is commercialized.

The development of pre-implantation genetic diagnosis (PGD) pushed artificial reproductive technology to a new level of genetic manipulation. It is no longer sufficient to conceive a child, but that child must now be defect free. Embryos are conceived through IVF, but before they are implanted in the uterus, their DNA is screened for chromosomal abnormalities. Embryos found to have undesirable genetics are discarded as medical waste with no regard for their humanity. These nascent human beings may be destroyed because they have chromosomal patterns linked to diseases like Down syndrome or Trisomy 18, or they may have the gene linked to familial cancers, or they may just be the wrong sex. Sex-selection abortions and sex-selection of embryos for implantation have led to serious gender imbalances in countries like China and India where sons are highly preferred over daughters.

If one can select against undesirable traits, the next logical leap is to choose embryos that have desirable features. With the help of a billion dollar investment from the Chinese government, the Chinese firm B.G.I. is working to make selecting the most intelligent embryo a viable option. It is not unreasonable to think that the selection for other traits such as physical attractiveness or athletic ability cannot be far behind.

The idea of building the perfect child is part of the philosophical principle of procreative beneficence. The term was coined by Oxford professor Julian Savulescu, and refers to a form of utilitarianism that asserts parents have a moral obligation to produce the best child possible. The utilitarian foundation of his reasoning only values those who produce a material benefit to others. The sick, the weak, and the disabled drain resources and are therefore disposable. Professor Savulescu freely admits this amounts to eugenics. He justifies it as providing the greatest good to most people. However, the good that he seeks only benefits the strong and powerful, and is obtained at the expense of the weak and vulnerable.

Current reproductive technology requires fully formed gametes, ova and sperm, to produce human embryos. What if that requirement was removed? The next big leap in artificial reproductive technology is in vitro gametogenesis. Adult or embryonic stem cells are manipulated in the laboratory to function as gametes. This removes the need for both male and female donors. Ova and sperm can be produced from stem cells from either a man or a woman. This would allow same-sex couples to have children that are genetically related to both partners. Theoretically, in vitro gametogenesis could allow a single person to use his own cells to produce two gametes and have a child with only one biological parent.

In a 2013 article in the Journal of Medical Ethics,Dr. Robert Sparrow of Monach University in Australia invokes Savulescus procreative beneficence and outlines the potential uses of in vitro gametogenesis. He suggests that this technology would allow the breeding of better humans. Embryos could be produced and screened for desirable traits. Instead of implanting these embryos for gestation, their stem cells could be harvested and used to make more gametes. These would be used to make another generation of embryos that are again screened and selected. This process could be repeated again and again until the desired refinement of the genome is achieved. The embryo who is ultimately selected for full gestation may actually be several generations removed from his last relative who was actually born. Dr. Sparrow points out that the use of in vitro gametogenesis could shorten the time span between successive generations to a matter of months instead of a matter of decades.

In vitro gametogenesis does not require naturally formed gametes, but it does require naturally formed DNA. Dr. Jef Boeke and his research team, working at both Johns Hopkins University in Baltimore and New York University, are working to remove even that constraint. They have successfully constructed the first synthetic yeast chromosome. The yeast has a cell structure very similar to humans, so this work is seen as the first steps towards producing a completely synthetic human genome. While the research is in its infancy, the ultimate goal is mind-boggling. Children that have no biological parents could be produced from gametes made with synthetic DNA. Their DNA would be designed in the laboratory to meet the specifications of whoever is commissioning their creation.

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Artificial Reproductive Technology: Constructing a Dystopia