Category Archives: Human Genetics

By Dr Leora Fox August 30, 2021 Edited by Dr Sarah Hernandez

A team of scientists recently created an innovative genetic system where a drug taken by mouth could be used to control the action of a gene editor, like those used in CRISPR systems. This has useful applications for research studies in cells and animals, and perhaps most importantly, could lead to improvements in the safety and accuracy of future gene therapies in humans. The technology can be applied broadly for studying genes and diseases, and was developed by researchers with HD expertise, incorporating a drug that is relevant to HD. Though actual clinical trials are a long way off, the company that has recently licensed the technology has an existing interest in HD.

Although the methods for delivery of gene therapies have improved vastly in recent years, it hasnt yet been possible to control the actions of those therapies once they reach their targets in the brain or other parts of the body. Ideally, when modifying human genetics, wed want to be able to fine-tune things like the location of the genetic change, the amount of change that occurs at once, and the ability to stop the change in surrounding cells if it proves harmful those last two have proved to be a particular challenge in gene editing, until now.

A recently developed genetic switch system, dubbed Xon, addresses some of these challenges in a novel way. It was created by a team of scientists led by Beverly Davidson at the Childrens Hospital of Philadelphia, joined by researchers at the pharmaceutical company Novartis. The idea behind Xon was to create a gene editing technology that could be precisely delivered and then controlled over time using a drug that acts like an on/off switch.

Imagine a red traffic light that is on all the time, and can only be disabled with a special tool. Theres no way to move forward until the red light turns off. With the Xon system, scientists can put a stoplight in front of any gene, by inserting the gene and the stoplight together into a genetic package and delivering it to cells in a dish or in a living animal. The new gene is present but inactive, meaning it cant produce messages or proteins, until the stoplight is removed. But when a particular drug reaches the cell, it acts as the tool that turns off the genetic stoplight, activating the gene.

The reason that this is an exciting scientific innovation is that the Xon system allows researchers to insert a gene and turn it on and off by simply adding a drug to a dish of growing cells, or by giving the drug to a research animal. This could be a new way to understand what happens when there is too much or too little of a given gene or protein, or to create a disease model to easily explore genetic interventions at different time points during aging.

In a recent publication in the journal Nature, Davidsons team tested the technology using a variety of genes involved in neurodegenerative diseases and cancers to show that their levels could be controlled based on when and how much of the stoplight-disabler drug was given.

Even more interesting is the potential application of the Xon system to technologies like CRISPR and the future of gene editing as a therapeutic. This recent paper demonstrates the ability of the Xon system to be combined with CRISPR-Cas9 technology, for more precise control of CRISPR editing using a drug fed to mice. Davidsons team demonstrated this using an artificial gene that can make a mouses liver cells glow green. But ultimately the hope is that it could be applied to human therapies.

A system that can help us gain better control of CRISPR gene editing is an exciting prospect because it provides more hope of safely adapting this technology for future medicines. This is not currently possible for most diseases, because direct, irreversible changes to human DNA can have drastic consequences. We wrote recently about the first ever successful safety trial of a CRISPR drug for a human disease that commonly affects the liver. Although it would be marvelous in theory to cut out or correct the HD gene in people, the knife-like CRISPR system almost always leads to additional unwanted changes in other genes. This is why weve so often emphasized that gene editing needs to come a long way before we can apply it to the treatment of human brain cells, which cant be regenerated like cells in the liver.

Coupling Xon with a CRISPR-Cas9 system that targets a disease gene (like the HD gene) would mean that an oral drug could turn the gene editor on and off. The dose could also be adjusted to control the amount of gene editing not just acting as a tool to disable the red stoplight, but also acting as a dimmer switch for precise regulation. Most importantly for safety, if anything went awry, the treatment could be stopped to prevent further changes to their DNA. Right now this is all theoretical, because the Xon system and other gene editing dimmer switches are in early developmental stages. Nevertheless, this publication hints at the possibility of applying it to therapies in people, and Novartis has licensed the Xon technology.

First and foremost, we know that HD is caused by a change to a single gene, so it has always been a prime candidate for genetic therapies, and dozens of researchers and companies worldwide are developing innovative solutions to treat HD at its source. HDBuzz (and HD researchers) always have an eye out for new technologies that improve upon existing methods. Furthermore, the leaders of the team that published the recent Nature paper are respected HD researchers who have devoted much of their careers to the development of gene therapies.

However, the main reason this publication has popped up as news for the HD community is that the Xon system actually relies on an existing drug to flip the gene editing switch and that drug is none other than branaplam. Yep, branaplam, the oral drug developed to treat children with SMA, which Novartis will soon be testing in clinical trials for adults with Huntingtons disease.

This does not mean that Xon gene editing has any part in upcoming trials for HD. It simply means that branaplam, a drug with genetic cut-and-paste abilities, forms part of an elegant new system that can be adjusted to control the activity of any gene scientists want to study. Dimmer switch systems for gene editing could potentially be designed to use a completely different drug, but in these early experiments, Xon and its precise control with branaplam has stood up to many tests of flexibility and accuracy.

The Xon system is a really cool early-stage technology, and though its not ready to be applied to human treatments, it is a novel element of the gene editing toolbox. Furthermore, it was created by researchers with HD expertise, and has now been licensed by a major pharmaceutical company which is already invested in HD therapeutics. That bodes well for its continued development in the study and potential treatment of HD and related genetic disorders.

See the original post:
Another tool in the box: Creation of a molecular dimmer switch advances gene editing - HDBuzz

A new study by theUniversity of Oxford, Baylor College of Medicine, theUniversity of Wisconsin-Madison, and Bayer AG have identified the genetic cause of endometriosis and potential drug target. This groundbreaking discovery was achieved by performing genetic analyses of humans and rhesus macaques. Scientists offered new insight into treating this debilitating disease, which is welcome news for the 1 in 10 women who suffer from this debilitating disease.

What is endometriosis?

Endometriosis (pronounced en-doe-me-tree-O-sis) is a chronic and painful disease in which tissue similar to the tissue that normally lines the inside of the uterus (the endometrium),grows outside the uterus. Endometriosis most commonly targets the ovaries, fallopian tubes, and the tissue lining the pelvis. Seldomly, endometrial-like tissue may be found in the intestines.

With endometriosis, the endometrial-like tissue acts as endometrial tissue would in a healthy woman. It thickens, breaks down, and bleeds with each menstrual cycle.

However, as this tissue has no way to exit the body, it becomes trapped. This is where the problems start.

When endometriosis involves the ovaries, cysts calledendometriomasmay form. The surrounding tissue may become irritated, eventually developing into scar tissue and adhesions (bands of fibrous tissue that can cause pelvic tissues and organs to stick to each other).

Endometriosis causes pain, sometimes severe pain; especially during menstrual periods. Fertility problems can also develop. Fortunately, effective treatments are available but are limited.

Lets delve into the details

Scientists found that a specific gene calledNPSR1increases the risk of endometriosis. The results uncovered a potential drug target for improved endometriosis therapy, which is currently quite limited.

In an earlier study, scientists discovered a genetic linkage to endometriosis on chromosome7p13-15 in DNA. Subsequently, this finding was confirmed in the DNA of rhesus monkeys with spontaneous endometriosis.

This validation supported further research through in-depth sequencing analysis of the endometriosis families at Oxford, which narrowed down the genetic cause to rare variants in the NPSR1 gene.

This new study involved more than 11,000 women, including patients with endometriosis and healthy women. They identified a specific common variant in the NPSR1 gene also associated with stage III/IV endometriosis.

Jeffrey Rogers, Associate Professor at the Human Genome Sequencing Center at Baylor, expressed his enthusiasm at these findings:

This is one of the first examples of DNA sequencing in nonhuman primates to validate results in human studies and the first to make a significant impact on understanding the genetics of common, complex metabolic diseases. The primate research helped to provide confidence at each step of the genetic analysis in humans and gave us the motivation to carry on chasing these particular genes.

Using NPSR1 inhibitors, scientists blocked the protein signalling of that gene in cellular assays. In doing so, they were able to reduce inflammation and abdominal pain. This treatment identified a target for future research in treating endometriosis.

Krina Zondervan, Professor of Reproductive and Genomic Epidemiology, further commented on the findings:

This is an exciting new development in our quest for new treatments of endometriosis, a debilitating and underrecognized disease affecting 190 million women worldwide. We need to do further research on the mechanism of action and the role of the genetic variants in the modulation of the genes effects in specific tissues.

However, we have a promising new nonhormonal target for further investigation and development that appears to address the inflammatory and pain components of the disease directly.

These findings are welcome news to the millions of women who suffer from Endometriosis and provide some peace of mind to those who have been newly diagnosed.

The findings in this article were taken from the journalNeuropeptide S receptor 1 is a nonhormonal treatment target in endometriosis.

Read more from the research article,here.

See original here:
Breakthrough: Scientists Have Identified Genetic Cause Of Endometriosis, Leading To Potential Treatment - GreekCityTimes.com

PAY ATTENTION: Click See First under the Following tab to see Briefly News on your News Feed!

Aisha Pandor is a stunning local woman who is celebrated for being an inspiration after launching her company known as SweepSouth. The company is Africas first online end-to-end platform for booking, managing, and paying for home cleaning services.

According to a Facebook post shared by Sapientis Advisory, Pandor is the co-founder and CEO of SweepSouth, and she is one of very few black female tech startup CEOs both in South Africa and internationally.

According to media reports, Pandors company has expanded into Kenya and are poised to launch in Nigeria. The bubbly woman is celebrated on social media platforms for her ambitions and influence on many locals and Africans.

Women24 reports that Pandor is a proud holder of a PhD in Human Genetics through the University of Cape Town.

Enjoy reading our stories? Download the BRIEFLY NEWS app on Google Play now and stay up-to-date with major South African news!

The post reads:

@Matshidiso Kgokong said:

@Cathryn Halliwell said:

@Snenhlanhla Shabangu said:

@Vanessa James said:

@Mawethu Jafta said:

@Tebello Finger said:

@Elbert Janse Van Resburg said:

In a similar story, Briefly News reported that Ncumisa Miesah Mkabile shared her inspiring story of making it through the pandemic. Ncumisa had to close down her takeaway business, which was her only source of income, but this did not stop her from working hard.

The 27-year-old started selling chicken and going door to door to do her deliveries.

After realising there was a demand for supplies from others who wanted to start their own business, Ncumisa jumped at the gap in the market. In late May 2020, Ncumisa got her hands on some land where she planted 20 000 spinach seeds.

She got more land a few months later where she planted 20 000 green pepper seeds and now supplies huge supermarkets.

Source: Briefly.co.za

See original here:
Meet Aisha Pandor: The Scientist With PhD and Started Own International Company South Africa news - Briefly

There are people who argue, persuasively, that Hollywood films are worse than they used to be. Or that novels have turned inward, away from the form-breaking gestures of decades past. In fact, almost anything can be slotted into a narrative of decline the planet, most obviously, but also (per our former president) toilets and refrigerators. One of the few arenas immune to this criticism is science: I doubt there are very many people nostalgic for the days before the theory of relativity or the invention of penicillin. Over the centuries, science has just kept racking up the wins. But which of these wins limiting ourselves to the last half-century mattered most? What is the most important scientific development of the last 50 years? For this weeks Giz Asks, we reached out to a number of experts to find out.

Research Assistant, Social Sciences, Humboldt University of Berlin

A bit more than 50 years ago, but I would say the most influential were the related developments of the Journal Impact Factor and the Science Citation Index (precursor of todays Web of Science) by Eugene Garfield and Irving H. Sher between 1955 and 1961.

These developments laid the groundwork for current regimes of governance and evaluation in academia. Their influence on the structure of science as we know it can hardly be overestimated: Today, it is difficult to imagine any funding, hiring, or publication decision that does not draw in some way either directly on the JIF or data from the Web of Science, or at least on some other form of quantitative assessment and/or large-scale literature database. Additionally, the way we engage with academic literature and hence how we learn about and build on research results has also fundamentally been shaped by those databases.

As such, they influence which other scientific developments were made possible in the last 50 years. Some groundbreaking discoveries might have only been possible under this regime of evaluation of the JIF and the SCI, because those projects might not have been funded under a different regime but also, its possible that we missed out on some amazing developments because they did not (promise to) perform well in terms of quantitative assessment and were discarded early on. Current debates also highlight the perverse and negative effects of quantitative evaluation regimes that place such a premium on publications: goal displacement, gaming of metrics, and increased pressure to publish for early career researchers, to name just a few. So while those two developments are extremely influential, they are neither the only nor necessarily the best possible option for academic governance.

Professor, History of Science, Stanford University, whose research focuses on 20th century science, technology, and medicine

That would surely be the discovery and proof of global warming. Of course, pieces of that puzzle were figured out more than a century ago: John Tyndall in the 1850s, for example, showed that certain gases trap rays from the sun, keeping our atmosphere in the toasty zone. Svante Arrhenius in 1896 then showed that a hypothetical doubling of CO2, one of the main greenhouse gases, would cause a predictable amount of warming which for him, in Sweden, was a good thing.

It wasnt until the late 1950s, however, that we had good measurements of the rate at which carbon was entering our air. A chemist by the name of Charles Keeling set up a monitoring station atop the Mauna Loa volcano in Hawaii, and soon thereafter noticed a steady annual increase of atmospheric CO2. Keelings first measurements showed 315 parts per million and growing, at about 1.3 parts per million per year. Edward Teller, father of the H-bomb, in 1959 warned oil elites about a future of melting ice caps and Manhattan under water, and in 1979 the secret sect of scientists known as the Jasons confirmed the severity of the warming we could expect. A global scientific consensus on the reality of warming was achieved in 1990, when the Intergovernmental Panel on Climate Change produced its first report.

Today we live with atmospheric CO2 in excess of 420 parts per million, a number that is still surging every year. Ice core and sea sediment studies have shown that we now have more carbon in our air than at any time in the last 4 million years: the last time CO2 was this high, most of Florida was underwater and 24.38 m sharks with 8-inch teeth roamed the oceans.

Coincident with this proof of warming has been the recognition that the history of the earth is a history of upheaval. Weve learned that every few million years Africa rams up against Europe at the Straits of Gibraltar, causing the Mediterranean to desiccate which is why there are canyons under every river feeding that sea. We know that the bursting of great glacial lakes created the Scablands of eastern Washington State, but also the channel that now divides France from Great Britain. We know that the moon was formed when a Mars-sized planet crashed into the earth and that the dinosaurs were killed by an Everest-sized meteor that slammed into the Yucatan some 66 million years ago, pulverizing billions of tons of rock and strewing iridium all over the globe. All of these things have been only recently proven. Science-wise, we are living an era of neo-geocatastrophism.

Two things are different about our current climate crisis, however.

First is the fact that humans are driving the disaster. The burning of fossil fuels is a crime against all life on earth, or at least those parts we care most about. Pine bark beetles now overwinter without freezing, giving rise to yellowed trees of death. Coral reefs dissolve, as the oceans acidify. Biodisasters will multiply as storms rip ever harder, and climate fires burn hotter and for longer. Organisms large and small will migrate to escape the heat, with unknown consequences. The paradox is that all these maladies are entirely preventable: we cannot predict the next gamma-ray burst or solar storm, but we certainly know enough to fix the current climate crisis.

The second novelty is the killer, however. For unlike death-dealing asteroids or gamma rays, there is a cabal of conniving corporations laboring to ensure the continued burning of fossil fuels. Compliant governments are co-conspirators in this crime against the planet along with think tanks like the American Petroleum Institute and a dozen-odd other bill-to-shill institutes. This makes the climate crisis different from most previous catastrophes or epidemics. It is as if the malaria mosquito had lobbyists in Congress, or Covid had an army of attorneys. Welcome to the Anthropocene, the Pyrocene, the Age of Agnotology!

So forget the past fifty years: the discovery of this slow boil from oil could well become the most important scientific discovery in all of human history. What else even comes close?

Professor and Chair, History of Science, The University of Oklahoma

Id say the best candidate is the set of ideas and techniques associated with sequencing genes and mapping genomes.

As with most revolutionary developments in science, the genetic sequencing and mapping revolution wasnt launched by a singular discovery; rather, a cluster of new ideas, tools, and techniques, all related to manipulating and mapping genetic material, emerged around the same time. These new ideas, tools, and techniques supported each other, enabling a cascade of continuing invention and discovery, laying the groundwork for feats such as the mapping of the human genome and the development of the CRISPR technique for genetic manipulation.

Probably the most important of these foundational developments were those associated with recombinant DNA (which allow one to experiment with specific fragments of DNA), with PCR (the polymerase chain reaction, used to duplicate sections of DNA precisely, and in quantity), and with gene sequencing (used to determine the sequences of base pairs in a section of DNA, and thus to identify genes and locate them relative to one another).

While each of these depended upon earlier ideas and techniques, they all took marked steps forward in the 1970s, laying the foundation for rapid growth in the ability to manipulate genetic material and to map genes within the larger genomes of individual organisms. The Human Genome Project, which officially ran from 1990-2003, invested enormous resources into this enterprise, spurring startling growth in the speed and accuracy of gene sequencing.

The ramifications of this cluster of developments, both intellectual and practical, have been enormous. One the practical side, the use of DNA evidence in criminal investigation (or in exonerating the wrongly convicted), is now routine, and the potential for precise, real-time genomic identification (and surveillance) is being realised at a startling pace. While gene therapies are still in their infancy, the potential they offer is tantalising, and genomic medicine is growing rapidly.

Pharmaceutical companies now request DNA samples from individual experimental subjects in clinical trials in order to correlate drug efficacy with aspects of their genomes. And, perhaps most important of all, the public health aspects of gene sequencing and mapping are stunning: the genome of the SARS-2 Coronavirus that causes Covid-19 was sequenced by the end of February 2020, within weeks of the realisation that it could pose a serious public health threat, and whole-genome analysis of virus samples from around the world, over time, have enabled public health experts to map its spread and the emergence of variants in ways that would have been unthinkable even a decade ago.

The unique aspects of the virus that make it so infectious were identified with startling speed, and work on an entirely new mode of vaccine development began, leading to the development, testing, and mass production of a new class of vaccines (mRNA vaccines) of remarkable efficacy, in unbelievably short time less than a year from identification of the virus to approval and wide use. It is hard to overstate how amazing this novel form of vaccine development has been, and how large its potential is for future vaccines.

On the intellectual/cultural side, the collection of techniques for manipulating and mapping genetic material is challenging longstanding ideas about what is natural and about what makes us human. Organic, living things now can be plausibly described as technologies, and thats an unsettling thing. Aspects of our individual biological identities that once were givens are increasingly becoming choices, with implications we are just beginning to see.

In addition, these same techniques are being deployed to reconstruct our understanding of evolutionary history, including our own evolution and dispersal across the globe, and perhaps nothing is more significant than changing how we understand ourselves and our history.

Professor, Science and Technology Studies, University College London, who researches the history of modern science and technology

My answer would be PCR Polymerase Chain Reaction. Invented by Kary Mullis at the Cetus Corporation in California in 1985, its as important to modern genetics and molecular biology as the triode and the transistor to modern electronics. Indeed it has the same role: its an amplifier. DNA can be multiplied. Its a DNA photocopier.

Without it, especially once automated, much modern genetics would be extremely time-consuming, laborious handcraft, insanely expensive, and many of its applications would not be feasible. It enables sequencing and genetic fingerprinting, and we have it to thank for COVID tests and vaccine development. Plus, you can turn it into a fantastic song by adapting the lyrics to Sleaford Mods TCR. Singalong now: P! C! R! Polymerase! Chain! Reaction!

Read this article:
What Is the Most Important Scientific Development of the Last 50 Years? - Gizmodo Australia

The Department of Genetics and Human Genetics offers courses leading to the Master of Science and Doctor of Philosophy degrees . The program is associated with the Departments of Pediatrics and Biology so that students will not only learn to work creatively in their own field of special interest but will also be able to relate their findings to progress made in related disciplines.

The graduate programs in Genetics & Human Genetics are designed to confer the training standards that will develop students for degrees of Doctorate of Philosophy Masters, and M.D./Ph.D. degree(s). The graduate program is an interdepartmental entity built on a diverse platform.

The program is associated with the department of Pediatrics and department of Biology where students work creatively in their field of special interest but and be able to relate application and relevance to related clinical and science disciplines.

The degree programs are designed to provide a curricular foundation in human genetics for all enrolled students during their first year.Following this, guided by their academic adviser, students elect to pursue their area of interest in genetics . This is accomplished through a combination of elective courses offered in the Department and other departments of the University, as well as in the Washington Area Consortium of Universities. The Masters thesis and Doctoral dissertation research interests likewise can reflect a broad range of interests, provided a suitable research mentor is identified in the graduate faculty.

This training program design takes into account the fact that genetics is increasingly relevant within the framework of multiple biomedical research and scholarly pursuits. The program design also is intended to foster the important principle of collaborative research and scholarship among biomedical disiplines.

The graduate programs are research-oriented curriculum's in the study of genetic mechanisms related to the transition from normal to disease states and intended to prepare graduates to participate in laboratory research.

To be accepted into the Graduate Program in Genetics and Human Genetics, students must have a Bachelors degree from an accredited institution and a GPA of at least 3.0 or B equivalent. In addition, students must meet the University requirement(s) to take the Graduate Record Examination (and the TOEFL if applicable).

Students with a bachelor degree may enter the graduate program at the Masters level or directly into the Ph.D. program. Eligibility to be considered for direct admission as a Ph.D. student requires a cumulative GPA greater than 3.2 and prior research and/or training experience in during undergraduate school or during a previous Masters degree

Applicants are required to submit these items for consideration of acceptance and review of potential for success:

Students wishing to enter the master's program should have a baccalaureate degree and a cumulative GPA average of B or the equivalent. They also should have completed undergraduate courses in modern biology, chemistry through organic chemistry, general biochemistry, mathematics through calculus, and general genetics, or equivalent courses. These prerequisites apply regardless of specialization selected within the master's program.

Students with less than a B average or who have not completed all of the required undergraduate courses may be admitted conditionally if they have very high Graduate Record Examination scores and/or excellent recommendations.

Students may matriculate into the doctoral program, having completed a suitable Masters degree, provided they present evidence of previous research experience supported by excellent letters of recommendation, and grades above 3.2 average.

Students who do not meet these general criteria may be considered for the master's program as indicated above.

CORE COURSES AND COURSE OFFERINGS

Fall semester ( yr 1)

Spring semester (yr 1)

Fall Semester (yr 2)

Spring Semester (yr 2)

GENETIGENETICS AND HUMAN GENETICS COURSE DESCRIPTIONS

Intro to Biochemical Genetics 219 (6cr) Fall only (MWF) - This 6-credit course is designed as an introductory course in biochemistry with special emphasis on those areas of biochemistry that are especially relevant to genetics and human genetics. The course is team-taught using faculty members and guest lecturers who have particular interest or training in each topic to be covered. The course is organized around four major units: Proteins and Enzymes, Nucleic Acids, Hormones, and Metabolism. The course is designed to develop a students; recall of cellular biochemistry, knowledge base of the relationship between the genetic code and the translation of biochemical pathways in disease pathology, comprehension of the relationship between pathological genetic changes to the biological process that cause human disorders.

Research in Genetics 220 GC (1-9cr). This course provides academic credit for independent research. It is offered on a variable credit basis and students may elect to register for 1 to 9 credits, depending on the level of time commitment to research the student expects to dedicate. In most cases, the research conducted in this venue is research under the guidance of a faculty mentor of the students choosing leading to a masters thesis or doctoral dissertation. This course is structured so that Masters and Doctoral students can focus on and perform literature research, identify mentors & research projects, and conduct thesis and dissertation research in the Department of Genetics & Human Genetics. Because research is rarely completed in a single semester, this course may be taken repeatedly until the research is concluded and the thesis or dissertation judged to have passed.

Hum Biochemistry & Molecular Gene 222 (4cr). This course explores the biochemical characteristics of variation in human genetic material and in corresponding gene products. This requires integrating information on gene structure, regulation of gene expression, gene product, and the physiological/anatomical phenotypes which reflect mutations. This course addresses concepts of intragenic repetitive sequences, DNA methylation, imprinting, genetic heterogeneity as it relates to genotype-phenotype correlation. The molecular evolution of specific genes are explored through both orthologous and paralogous sequence homologies. The goals of the course is to develop familiarity with a sample of genetic disorders distributed over various human anatomic, biochemical, and physiological systems, develop skills in integrating inherited abnormalities in molecular and biochemical structures as rational explanations for selected phenotypes. The format of the course consists of lectures by a spectrum of clinicians and researchers who have a high degree of familiarity with their subject matter.

Human Genetics I 223 GC (3cr) Fall only. The course is distributed over two semesters as Human Genetics I & II. This course offers a careful study of the conceptual terrain for the discipline to develop a working familiarity with many of the central concepts in contemporary human genetics, recognize the roles of technology and human values in shaping the central concepts, develop proficiency in analyzing models of heritable variation and corresponding phenotypic expression, and their distributions in pedigrees and populations, and to identify evidence for interactions between gene expressions and environment to yield phenotypes. The course format combines lecture, discussion, assigned readings to provide further content depth and breadth.

Human Genetics II 224 (3cr) This course is a continuation of Human Genetics I. This course will cover a minimum of 30 multifactorial phenotypes (congenital malformations and late onset disorders). This course distinguishes and characterizes each of the models of inheritance as it pertains to relationships between genes and phenotype. Its designed to cover principles of multifactorial or polygenic models for estimating empiric recurrence probabilities, correlations between genetic and environmental factors of phenotypic value and heritabilities. One goal is to identify the spectrum of approaches currently envisioned for medical intervention in genetic disorders.

Cytogenetics 229 (3cr). This course is designed to develop a basic understanding of cytogenetics. The course covers chromosomal abnormalities and the etiology of how chromosomal aberrations contribute to congenital disease and cancer. The course will provide in-depth content and focus on cytogenetic and molecular cytogenetic diagnostic techniques. The goal of this course is to have students become proficient in preparing detailed genetic counseling case studies.

Seminar in Genetics 229 (2cr). This course is offered each semester and current residents are invited to register continuously. Course format involves student participation in group discussion and article presentation each class period. The course is designed to focus on acquiring familiarity with current research in basic, clinical, and translational genetic disorders presented in various peer reviewed journals. The format promotes developing skillsets for; gathering, organizing, validating, and interpreting data of peer reviewed articles in molecular, biochemical, clinical, and population genetics. Students will develop the knowledge base to identify and compare the quality of molecular techniques and analytical tools used to perform research. The goal is to acquire skills to employ information from peered reviewed publications as a guide to understanding molecular evolution and forming individual research hypothesis.

Introduction to Medical Genetics 231 (3cr) This course introduces students to the clinical aspect of a broad range of human genetic disorders, focusing on phenotypic characteristics, current confirmatory diagnostic techniques for each disorder, and approaches to interventions in terms of either prevention of occurrence, reduced morbidity, or achieving improved coping with disease. The course is designed to develop a students ability to construct pedigrees and to interpret modes of inheritance. Course formats consists lectures organized in a case study format such that an integration of all components of phenotype can be understood in relation to rationale for diagnostic methodology, and relevant intervention approaches. Students perform assigned reading, on-line searches on genetic diseases.

Intro to Research in Genetics 233 (3cr) This course is required for all Masters and Ph.D. students in the first year. The course is designed for development of a hypothetical research project and writing of a detailed research proposal as a semester-long exercise. The course objective is to acquaint the student with a multitude of issues that bear on the successful conduct of independent research which include; understanding how to conduct literature searches, development of a hypothesis, identification of specific aims that will test the hypothesis, experimental design using principles of the scientific method, preparation and presentation of a written research proposal. This exercise will prepare the student for developing a thesis or dissertation proposal.

Gene Structure & Action 236 (2cr). This course explores the molecular process by which the synthesis, expression, and manipulation of genetic material is organized in chromatin and in cis-acting elements governing the process of the central dogma. It will include a critical review of gene organization, regulation of gene expression by hormones, growth factors, and oxidant stress emphasizing signal transduction pathways and the action of ligand-receptor mediated transcription regulators. Attention will be paid to regulation of gene expression, transcription, and translation by RNA interference and natural & synthetic xenobiotics. The goal of this course os to understand the nature and function of gene expression in proliferation, differentiation, and apoptosis in development and disease.

Psychosocial Aspects of Gene Disorders 312 (3cr) Analyzes psychosocial consequences of genetic disorders for each member of the family, impacts on life plan, decision-making, coping strategies, and approaches to counseling for such psychosocial consequences. Case studies are included together with development of skills in psychosocial interviewing and pedigree construction. Enrollment is limited.

Ethical, Legal, Social Issues in Medicine 313 (3cr) This course introduces students to ethical and bioethical issues confronting healthcare providers in the context of health care delivery and research. Students are introduced to the main theories and principles of bioethics and the moral foundations of patient-provider relationships, professionalism, relevant ethical and legal considerations and the concepts of moral reasoning. By utilizing the Bebeau Grid method to collect and analyze case information, students to develop the critical thinking skills necessary to identify and analyze ethical dilemmas and to construct well-reasoned responses to the dilemmas and resolving case material presented in the small group class sessions.

Cancer Genetics I: Clinical Aspects of Cancer 315 (3cr). This advanced elective course focuses on the genetics of cancer, specifically clinical aspects of cancer. Course format follows two hours of didactic lectures with one hour of an active learning component, bioinformatics and labs. This course will provoke dialogue by engaging class participation in questions & answers, as well as targeted discussions of information on the lecture topic gathered from other resources. The course is designed as a valuable resource for mainly graduate and health professional trainees, with interests in genetics and clinical cancer genetics. This course serves as a prerequisite to Cancer Genetics II: Molecular Aspects of Cancer.

Mutation Human Genes 412 (2cr). This course is structured for research ideas and current advances in genetic and biochemical alterations as a tool for clinical and translation research. This entails an integration of current events and data into the learning modality that utilizes current peer reviewed journal articles. This course focuses on using the substantial array of literature and bioinformatics to develop skills for analyzing data and addressing concepts of interpretation of data. Current peer reviewed publications are the materials used to generate an active learning education that supports group teaching, individual communication, and development of analytic skills. Course format is seminar based where students will present a 2-3 page written summary on the topic covering the molecular lesion, biochemical pathology, and a specific clinical disease associated with the genetic mutation of topic.

SPECIALIZED TRAINING COLLABORATIONS:

National Human Genome Center

As the only research center of its kind at a predominantly African American university, the National Human Genome Center (NHGC) is singular in its capacity to provide leadership for America and the global community in genetic studies of diseases common in African Americans and other people of color throughout the African Diaspora. In concert with the mission of Howard University, particular emphasis at the NHGC is placed on providing education opportunities of exceptional quality for African Americans and other historically disenfranchised groups. The NHGC is also dedicated to attracting, sustaining, and developing a cadre of research scientists, who through their investigations, are committed to reducing health disparities among ethnic groups, preventing disease and promoting health.

The National Human Genome Center (NHGC) Molecular Genetics Training Program accepts and supports promising students who seek research training in molecular genetics, genomics, and related clinical fields. The overall goal of these programs is to promote interdisciplinary, collaborative and innovative research training in areas relevant to the mission of the National Human Genome Center at Howard University.

The NHGC is a strong, valuable, and supportive center for supervising, training, and developing the professional scholarship if residents of the Genetics & Human Genetics department.

Research Center in Minority Institutions (RCMI)

The RCMI Program focuses on the enhancement and further development of the necessary research infrastructure which will ensure the Universitys ability to contribute to the investigation of diseases and provide collaborative consolidation of instrumentation, technical expertise, and support personnel to enhance the impact and availability. These research infrastructure components include the expansion of two research core laboratories: The Laboratory of Molecular Computations and Bioinformatics (LMCB), the Proteiomics Core Facility and the Biomedical NMR Laboratory (BNMR).

New efforts and programs are being developed to train Genetics students in bioinformatics and computational biology.

Sickle Cell Disease Center

The Center is committed to a six-fold goal that includes comprehensive medical care, research, testing, education, counseling, and community outreach. Recently, the Center has expanded its clinical research program and developed a collaborative consortium with Childrens National Medical Center (CNMC) and in working together with Howard University Hospital and NIH.

The Center has a long history of major participation and leadership in national and international research projects that have led to the development of effective therapies for sickle cell disease. With many of the basic molecular issues in sickle cell disease being better understood, major research efforts now focus primarily on clinical issues such as treatment for the disease.

The Center for Sickle Cell Disease offers clinical services and patient care:

The Center for sickle cell disease has trained Genetics students in research-intensive thesis and dissertation projects that have produced scholarly work.

http://www.sicklecell.howard.edu/

Cancer Center

Howard University Cancer Center (HUCC) is our natural ability and strength to address cancer disparities with an emphasis on those cancers that disproportionately impact African-Americans, in particular. There are three overarching programmatic areas in the Cancer Center: (1) cancer biology; (2) cancer etiology; and (3) cancer prevention, control, and population sciences; whereby cancer disparities represent the underlying theme of the research focus.

The ultimate goal of the Cancer Biology Program is to translate basic laboratory results from the bench to the bedside. Research activities that are currently underway in the cancer biology program include the following: (1) prostate cancer genetics; (2) methylation profiling and risk of colorectal cancer; (3) differential transcription factor activation of H. pylori; (4) triple negative breast cancer in young African-American women; (5) nicotine, biogenic amines and depression; and (6) in vivo NMR spectroscopy for noninvasive pharmacokinetics.

The Cancer Etiology Program focuses on epidemiologic research among predominantly African-Americans and underserved populations. This program examines risk factors that increase or decrease the likelihood of developing cancer risk and its precursors.

The Cancer Prevention, Control and Population Science Programs goal is to reduce the burden of cancer measured by incidence, morbidity, and mortality utilizing behavioral and clinical research interventions.

The department of Genetics and Human Genetics and the Division of Medical Genetics have faculty in the Cancer center that assist in the training and prospectus documents of our Ph.D., masters, and masters in counseling students.

http://cancer.howard.edu/about/overview.htm

The steps in the application process are as follows:

The application for the M.D./Ph.D. program should be returned to:

Kareem Washington, Ph.D.Director M.D./Ph.D. ProgramHoward University College of Medicine520 W Street, NWWashington, DC 20059email:kareem.washington @howard.edu

A student, with the advice of the director of graduate studies, may file for admission to candidacy.

Students in the Ph.D. program are required to spend at least three semesters in full-time residence, two of which must be consecutive.

Assistant Professor

Principal Invetsigator

Email

View Full Profile

Originally posted here:
Genetics and Human Genetics | Graduate School

The University Hospital Heidelberg is one of the major healthcare centers in Germany. Our objective is the development of innovative diagnostics and therapies as well as their quick implementation for the patient. With about 10,700 employees in more than 50 specialized clinical departments with almost 2,000 beds, about 80,000 patients in part-time and full-time inpatient treatment as well as 1,000,000 patients in ambulant treatment are medicated each year.

Postdoctoral position with combined wet and dry lab work at the Institute of Human Genetics (m/f/d)

JobID: P0025V441

at the earliest possible date searched for, AG Laugsch at the Institute of Human Genetics.

We are looking for an enthusiastic postdoc to join our research group at the Institute of Human Genetics of the University of Heidelberg. The position is limited to 3 years, with the option of further extension. The salary is based on TV-L salary groups.

Our laboratory explores the relationship between the head (craniofacial structures) and brain development in health and disease. We focus on developmental genes specifically and dynamically regulated, e.g., by enhancers. That regulation ensures the establishment of precise gene expression patterns during development, which might have pathological consequences when being disrupted.

Composed of international and multi-disciplinary scientists, our group creates a unique and inspiring environment and supports individual career development. For more information visit:

https://www.klinikum.uni-heidelberg.de/humangenetik/forschung/abt-humangenetik/ag-laugsch

(Magdalena Laugsch et al., Cell Stem Cell. 2019 May 2nd; Modelling the pathological longe-range regulatory effects of human structural variation with patient-specific hiPSC.;24(5):736-752)

Tasks and responsibilities

Creating and analyzing next-generation sequencing data, the successfull applicant will investigate the impact of cohesin on neural crest cells (hNCC) development and their contribution to Cornelia de Lange Syndrome (CdLS).

This rare but severe genetic disorder is caused by mutations in the cohesin complex or and its auxiliary factors and characterized by craniofacial and limbs malformations, heart defects, and cognitive deficits. Cohesin regulates the three-dimensional (3D) structure of chromatin and impacts the regulation of gene transcription. A large set of craniofacial abnormalities observed in CdLS patients most likely arises during the embryonic development of the hNCC. Hence, the postdoc will investigate the underlying molecular defects in hNCC derived from human induced pluripotent stem cells (hiPSC).

Combining genetic, epigenetic, and bioinformatic tools (hiPSC culture, CRISPR/Cas9 targeting, hNCC differentiation, RNA- and scRNA-seq, Hi-ChIP-seq, ATAC-seq, and analysis using advanced bioinformatics), the scientist will identify the 3D structure of chromatin and regulatory networks controlled by cohesin.

Your Profile

Ability to analyze your own data and significant proficiency as well as strong interest in Python, R, shell scripting and working with NGS data.

We offer

The application must include your motivation, a brief statement of your scientific interests, contact details from three references, curriculum vitae, separated publication list, and relevant certificates.

Please forward your complete application (in a single pdf document Filename: P0025V441_First Name_Second Name No other format will be accepted) by email.

Universittsklinikum Heidelberg

Institut fr Humangenetik

Dr. rer. nat. Magdalena Laugsch, Group Leader

Im Neuenheimer Feld 366

69120 Heidelberg

phone: +49 6221 56-39128

magdalena.laugsch@uni-heidelberg.de

The rest is here:
Postdoctoral position with combined wet and dry lab work at the - Nature.com

NEW YORK An international team of researchers has used transcriptomic data from ulcerative colitispatients to develop a predicted polygenic transcriptional risk score, or PPTRS,that can identify UC-affected individuals at fivefold elevated risk of progressing to surgical resection of the large bowel.

In a paper published on Thursday in the American Journal of Human Genetics, the Georgia Institute of Technology-led team noted that 5 percent to 10 percent of people with UC require bowel resection, or colectomy, within five years of diagnosis, but that polygenic risk scores based on genome-wide association studies generally don't provide meaningful prediction of progression to surgery. However, studies of Crohn's disease have shown that gene expression profiling of GWAS-significant genes provides some stratification of risk of progression to complicated disease through transcriptional risk scoring, or TRS.

In their paper, the researchers demonstrated that a measured TRS based on bulk rectal gene expression in a cohort of UC patients had a positive predictive value approaching 50 percent for colectomy. Single-cell profiling demonstrated that the disease-associated genes were active in multiple diverse cell types from both the epithelial and immune compartments, and expression quantitative trait locusanalysis identified genes with differential effects at baseline and the one-year follow-up, the researchers said. But for the most part, they found that differential expression associated with colectomy risk was independent of local genetic regulation.

Overall, their data suggested that prediction of gene expression from relatively small transcriptome datasets can be used in conjunction with transcriptome-wide association studies for stratification of risk of disease complications.

The researchers began by performing differential expression analysis between baseline rectal RNA-seq biopsies of individuals in the PROTECT multicenter pediatric inception cohort study of response to standardized colitis therapy. Analyses were done on 21 affected individuals who progressed to colectomy and 310 who did not. They identified downregulation of 783 transcripts in the individuals who underwent colectomy and upregulation of 1,405 transcripts overall.

They also obtained rectal biopsy RNA-seq data for 92 affected individuals at week 52 and observed a marked shift in gene expression at follow-up, prompting them to ask whether local regulation of the gene expression might contribute to this effect. They found that there were 72 SNPs that were significantly regulating 308 genes at both time points.

Further examination of the expression of colectomy-associated genes in a single-cell RNA-seq dataset obtained from rectal biopsies provided strong evidence that both epithelial and immune cells contributed to the risk of disease progression, the researchers said.

The researchers then performed a TWAS to capture the effects of all polymorphisms within 1 Mb of each transcript expressed in the PROTECT rectal biopsies and then used the weights to predict gene expression in a validation cohort from the UK Biobank. They tested for differential predicted gene expression in 70 percent of the validation samples and discovered about 800 genes either upregulated or downregulated in UC-affected individuals relative to non-IBD control individuals. They then derived a PPTRS for UC based on the effect sizes of the minor alleles and applied it to the remaining 30 percent of the validation samples, as well as to the PROTECT genotypes, and found that the PPTRS efficiently discriminated UC-affected individuals from non-IBD control individuals.

Significantly, it also discriminated the individuals who underwent colectomy versus those who didn't in both the UK Biobank and PROTECT.

"More extensive single-cell profiling, combined with cell-type-specific genetic analysis of gene expression, is likely to lead to the development of even better transcriptional risk signatures," the authors concluded. "It is also likely that such focused and personalized analysis may highlight specific pathological mechanisms active in particular affected individuals."

They did note, however, that these results were limited by the relatively small sample size of colectomies in the PROTECT study, and that validation of cross-ancestry assessments and the evaluation of the consistency of gene expression prediction across populations should be a high priority.

In an email, corresponding author and GIT researcher Greg Gibson noted that while the study's multiple layers of replication show that transcriptional profiling of the rectum greatly enhances risk stratification for risk of colectomy, this was not a clinical trial, so the approach is not yet approved for evaluation of patients.

"We hope that it will progress to implementation in the near future," he added."The prediction from genotypes alone is less likely to have clinical utility since the precision is still quite low, so that aspect is more research oriented."

He further noted that the approach he and his colleagues used could also be applied to a wide range of diseases, and that they are pursuing that research.

Read the original here:
Ulcerative Colitis Study Analyzes Gene Expression to Measure Risk of Progression to Surgery - GenomeWeb

SAN DIEGO, Aug. 26, 2021 (GLOBE NEWSWIRE) -- Bionano Genomics, Inc. (Nasdaq: BNGO) today announced the European Society of Human Genetics (ESHG) conference lineup featuring 11 customer presentations of optical genome mapping (OGM) data spanning three major clinical areas of application from 10 institutions and six countries. The clinical application areas represented below cover hematological malignancies, inherited genetic disorders and solid tumor analysis. The presentations are expected to cover the clinical utility of OGM across these application areas, along with the unique capabilities of Bionanos Saphyr system to detect all classes of structural variants, across the genome, at a superior resolution relative to traditional techniques. The ESHG conference is being held virtually starting this Saturday from August 28 - 31, 2021.

More than 3,400 participants are registered for this years ESHG meeting, which provides a platform for the dissemination of the most exciting advancements in the field of human genetics. The upcoming customer presentations featuring OGM data are listed below along with the associated clinical areas of application:

OGM Application Area

Presenter

Affiliation

Presentation/Poster Title

Hematological Malignancies

Dr. Anna Puiggros

Hospital del Mar, Barcelona, Spain

Analysis of genomic complexity in patients with chronic lymphocytic leukemia (CLL) using optical genome mapping

Dr. Jonathan L. Lhmann

Hannover Medical School, Hannover, Germany

The clinical utility of optical genome mapping for the assessment of genomic aberrations in acute lymphoblastic leukemia

Inherited Genetic Disorders

Dr. Caroline Schluth-Bolard

Universite Hospital de Lyon, France

What is the best solution to manage failures of chromosomal structural variations detection by short-read strategy?

Dr. Kornelia Neveling

Radboud University Medical Centre, Netherlands

Long-read technologies identify a hidden inverted duplication in a family with choroideremia

Dr. Valrie Race

Univ. Hosp. of Leuven, Leuven, Belgium

Bionano optical genome mapping and southern blot analysis for FSHD detection

Dr. Romain Nicolle

Hospital Necker-Enfants Malades, Paris, France

16p13.11p11.2 triplication syndrome: a new recognizable genomic disorder characterized by Bionano optical genome mapping and WGS

Dr. Jenny Schiller

MVZ Martinsried, Martinsried, Germany

Characterization of breakpoint regions of apparently balanced translocations by optical genome mapping

Dr. Viola Alesi

Bambino Ges Children's Hospital, Rome, Italy,

Optical Genome Mapping: where molecular techniques give up

Dr. Valeria Orlando

Bambino Ges Children's Hospital, Rome, Italy

Optical genome mapping: a cytogenetic revolution

Solid Tumor Analysis

Dr. Florentine Scharf

Medical Genetics Center Munich, Germany

Germline chromothripsis of the APC locus in a patient with adenomatous polyposis

Dr. Mariangela Sabatella

Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands

Optical Genome Mapping Identifies Germline Retrotransportation Insertion in SMARCB1 in Two Siblings with Atypical Teratoid Rhabdoid Tumor

We believe our progress in Europe, with the increased awareness of OGM and the development of the market there, has been outstanding, commented Erik Holmlin, PhD, CEO of Bionano Genomics. Thanks to key sites like Radboud, Leuven and Cochin, the OGM footprint has now expanded in Germany, Spain and Italy. With the growing installed base of Saphyr in Europe, we have seen these institutions and their research teams conduct ground-breaking research to help demonstrate the potential utility of OGM as an alternative to traditional cytogenetics methods for the identification of genome structural variations that can be more sensitive, give a faster time to results and be less expensive to implement when compared to traditional methods. We believe the momentum of research that has been building will continue as more supporting data, like the data that we expect the researchers to show this week at ESHG, are released from around the world.

Story continues

For more details and to register for this online event please go to https://vmx.m-anage.com/home/release/eshg2021/en-GB

About Bionano Genomics

Bionano is a genome analysis company providing tools and services based on its Saphyr system to scientists and clinicians conducting genetic research and patient testing, and providing diagnostic testing for those with autism spectrum disorder (ASD) and other neurodevelopmental disabilities through its Lineagen business. Bionanos Saphyr system is a research use only platform for ultra-sensitive and ultra-specific structural variation detection that enables researchers and clinicians to accelerate the search for new diagnostics and therapeutic targets and to streamline the study of changes in chromosomes, which is known as cytogenetics. The Saphyr system is comprised of an instrument, chip consumables, reagents and a suite of data analysis tools. Bionano provides genome analysis services to provide access to data generated by the Saphyr system for researchers who prefer not to adopt the Saphyr system in their labs. Lineagen has been providing genetic testing services to families and their healthcare providers for over nine years and has performed over 65,000 tests for those with neurodevelopmental concerns. For more information, visit http://www.bionanogenomics.com or http://www.lineagen.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as may, will, expect, plan, anticipate, estimate, intend and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) convey uncertainty of future events or outcomes and are intended to identify these forward-looking statements. Forward-looking statements include statements regarding our intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the timing, content and significance of the presentations identified in this press release; our assessments regarding our progress in the European market, including our expectations with respect to the continued adoption of OGM throughout Europe; the benefits of OGM relative to traditional cytogenetic testing methods and its potential to replace traditional cytogenetic methods; our assessments regarding current and future research by the institutions identified in this press release; and the execution of Bionanos strategy. Each of these forward-looking statements involves risks and uncertainties. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the risks and uncertainties associated with: potential inaccuracies in presentations given at the ESHG Conference or subsequently published data that may minimize the impact of OGM in human genetics; the impact of the COVID-19 pandemic on our business and the global economy; general market conditions; changes in the competitive landscape and the introduction of competitive products; changes in our strategic and commercial plans; our ability to obtain sufficient financing to fund our strategic plans and commercialization efforts; the ability of medical and research institutions to obtain funding to support adoption or continued use of our technologies; the loss of key members of management and our commercial team; and the risks and uncertainties associated with our business and financial condition in general, including the risks and uncertainties described in our filings with the Securities and Exchange Commission, including, without limitation, our Annual Report on Form 10-K for the year ended December 31, 2020 and in other filings subsequently made by us with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management's assumptions and estimates as of such date. We do not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

CONTACTSCompany Contact:Erik Holmlin, CEOBionano Genomics, Inc.+1 (858) 888-7610eholmlin@bionanogenomics.com

Investor Relations and Media Contact:Amy ConradJuniper Point+1 (858) 366-3243amy@juniper-point.com

Here is the original post:
Bionano Genomics Announces ESHG Lineup Featuring 11 Customer Presentations of OGM Data Spanning Three Major Clinical Research Areas of Application...

By Brian McNeill

An analysis of data from 1.5 million people has identified 579 locations in the genome associated with a predisposition to different behaviors and disorders related to self-regulation, including addiction and child behavioral problems.

With these findings, researchers have constructed a genetic risk score a number reflecting a persons overall genetic propensity based on how many risk variants they carry that predicts a range of behavioral, medical and social outcomes, including education levels, obesity, opioid use disorder, suicide, HIV infections, criminal convictions and unemployment.

[This study] illustrates that genes dont code for a particular disorder or outcome; there are no genes for substance use disorder, or for behavior problems, said joint senior authorDanielle Dick, Ph.D., Distinguished Commonwealth Professor of Psychology and Human and Molecular Genetics at Virginia Commonwealth University. Instead, genes influence the way our brains are wired, which can make us more at risk for certain outcomes. In this case, we find that there are genes that broadly influence self-control or impulsivity, and that this predisposition then confers risk for a variety of life outcomes.

The study, Multivariate Analysis of 1.5 Million People Identifies Genetic Associations with Traits Related to Self-Regulation and Addiction, was published today in the journal Nature Neuroscience and was conducted by a consortium of 26 researchers at 17 institutions in the United States and the Netherlands.

It was led by Dick;Philipp Koellinger, Ph.D., professor of social science genetics at the University of Wisconsin Madison and Vrije Universiteit Amsterdam;Kathryn Paige Harden, Ph.D., professor of psychology at the University of Texas at Austin; andAbraham A. Palmer, Ph.D., professor of psychiatry at the University of California, San Diego.

The study is one of the largest genome-wide association studies ever conducted, pooling data from an effective sample size of 1.5 million people of European descent. The researchers genetic risk score has one of the largest effect sizesa measurement of the prediction powerof any genetic risk score for a behavioral outcome to date.

It demonstrates the far-reaching effects of carrying a genetic liability toward lower self-control, impacting many important life outcomes, said Dick, a professor in the Department of Psychology in the College of Humanities and Sciences and the Department Human and Molecular Genetics in the School of Medicine at VCU. We hope that a greater understanding of how individual genetic differences contribute to vulnerability can reduce stigma and blame surrounding many of these behaviors, such as behavior problems in children and substance use disorders.

The identification of the more than 500 genetic loci is important, the researchers said, because it provides new insight into our understanding of behaviors and disorders related to self-regulation, collectively referred to as externalizing and that have a shared genetic liability.

We know that regulating behavior is a critical component of many important life outcomesfrom substance use and behavioral disorders, like ADHD, to medical outcomes ranging from suicide to obesity, to educational outcomes like college completion, Dick said.

Characterizing the genetic contributions to self-regulation can be helpful in myriad ways, she said.

It allows us to better understand the biology behind why some people are more at risk, which can assist with medication development, and it can allow us to know who is more at risk, so we can put early intervention and prevention programs in place, she said. Identifying genetic risk factors is a critical component of precision medicine, which has the goal of using information about an individuals genetic and environmental risk factors to deliver more tailored, effective intervention specific to that individuals risk profile.

The researchers noted, however, that having a higher risk profile isnt necessarily a bad thing.

For example, CEOs, entrepreneurs and fighter pilots are often higher on risk taking, Dick said. DNA is not destiny. We all have unique genetic codes, and were all at risk for something; but understanding ones predisposition can be empoweringit can help individuals understand their strengths, and their potential challenges, and act accordingly.

For more information about the study and its findings, please visit thisFAQ.

Subscribe to VCU News at newsletter.vcu.edu and receive a selection of stories, videos, photos, news clips and event listings in your inbox.

Excerpt from:
Study identifies 579 genetic locations linked to anti-social behavior, alcohol use, opioid addiction and more - VCU News

A $2 million grant from the Mass Life Sciences Center has helped launch the Comparative Pathology and Genomics Shared Resource at Cummings School of Veterinary Medicine, a shared resource with state-of-the-art equipment that fills newly renovated laboratory space. For Cheryl London, a veterinary oncologist and Associate Dean for Research and Graduate Education, it represents a long-time vision becoming reality.

Understanding the pathology of infectious diseases is more critical than ever, said London, who added that the resource will lead to improvements in the treatment and prevention of diseases in humans through detailed genetic characterization of model systems and the associated pathology across species.

London tapped two Cummings School faculty members to lead the effort: assistant professorAmanda Martinot, a veterinary pathologistwho focuses on infectious diseases such as SARS CoV-2 and tuberculosis, and assistant research professor Heather Gardner, GBS20, a veterinary oncologist and geneticist.

Cummings School has been investing in this goal for quite some time. In 2020, the 7,500-square-foot Peabody Pavilion was renovated into modern, flexible lab space designed to support multidisciplinary teams. In addition, the resource will leverage Tufts resources such as the New England Regional Biosafety Laboratory (RBL).

When fully operational, this resource will offer advanced capacities for credentialling and analyzing animal models of disease that will help to grow collaborative opportunities among regional academic and industry entities; provide training opportunities for students, fellows, scientists and clinicians; and ultimately support job growth through expansion of the research enterprise in Central Massachusetts, said London.

Martinots research has focused on tuberculosis (TB). When the Martinot Lab and her collaboratorsCummings School associate professor Gillian Beamer, Tufts University School of Medicineassociate professor Bree Aldridge, and Harvard University professor Peter Sorger, head of the Harvard Program in Therapeutic Sciencesidentified some rare lung biopsies and archived lung specimens from tuberculosis patients that were taken during autopsies many years ago, Martinot thought they were a natural pilot project for the Comparative Pathology and Genomics Shared Resource.

We're trying to understand the biology of tuberculosis in human tissue, what helps the body clear TB, and what fuels TB progression, said Martinot. We use a lot of animal models to try to understand these processes, but there's no animal model that perfectly mimics human TB disease.

The resources new technology can extract meaningful genetic information from the immune cells surrounding and within granulomas, a hallmark pathologic feature of tuberculosissomething they haven't been able to do before. This technology also will allow them to obtain similar information from a variety of pathology samples.

Another pilot project aims to advance research by London and Gardner in canine osteosarcoma, an aggressive bone cancer that affects more than 25,000 dogs each year. In 2019, they published findingsof a study that detailed the landscape of genetic mutations in canine osteosarcoma, and more recently completed a clinical trial to test a new immunotherapy treatment on dogs diagnosed with this type of cancer. TheClinical Trials Officeat Cummings School has treated a number of canine osteosarcoma patients, allowing banking of associated biologic samples for further investigation. With these tissue samples, investigators can ask questions about the molecular and genomic features of cancer over time and identify clinical and pathologic correlates.

Animals get a lot of the same diseases that people do, and the information we learn from animals with these diseases can inform investigation of novel research opportunities across species, said Gardner.

We can start to interrogate the combination of pathology with genetics and follow how the cancer is mutating, Martinot said. And we can look at where these cancer cells live to try to understand how the microenvironment might be supporting the progression of the cancer. That information could lead to potential treatment options.

Paul Mathew, anoncologist at Tufts Medical Center and an associate professor at Tufts School of Medicine, is interested in using the resources technology to ask similar questions about prostate cancer using biopsies from human patients. He wants to understand the tumor and how the microenvironment changes over time in prostate cancer patients. The School of Medicineis one of many potential users of the resourceothers include UMass Medical School and Medical Center, which has plans for a new Veterans Administration outpatient clinic and Institute for Human Genetics.

The resource is home to cutting edge new technology that integrates pathology and genomics, said Martinot. With the help of this grant, we can do whole genome sequencing for genetic analysis of pathogens, tumors, and anything imaginable where the DNA sequence might make a difference.

The goal is to help drive discovery, adds Gardner. We have equipment to support next generation sequencing projects, such as a liquid handler robot to help automate sample processing and an Illumina sequencer. We also have a suite of NanoString equipment, which is a platform that will allow increased use of samples historically considered difficult to work with, including formalin-fixed samples, which are often very degraded.

The new technology that will power this effort falls into two main categories:

Everyone involved with the shared resource is excited about its future potential and the opportunity to see it grow. As Gardner said, The opportunities to impact research, in all areas, are limited by the investigators imagination.

Angela Nelson can be reached atangela.nelson@tufts.edu.

Read the original here:
Investing in the Power of Pathology and Genomics - Tufts Now