Category Archives: Human Genetics

We have all heard of gut health and understand that it impacts our overall health in some way. But did you know that poor gut health has been linked to mood disorders and brain diseases like dementia?

Do you know what the gut or microbiome is? As a reminder, it's simply all the bacteria and microorganisms found in the gastrointestinal (GI) tract. And it has a huge impact on our health.

There are trillions of bacteria in the human gut, and they live in a symbiotic way to help us stay healthy. The average person will have about 30 trillion cells in their body. They will have around the same number of gut bacteria, give or take a few trillion. The point is that we are made up of bacteria, at least 43%. So, we are only half-human. We have our own human genome, and common wisdom is that our human genes determine and impact our health. In reality, the bacteria that reside within us also have a genome, and it is the interaction between the human genome and the bacterial genome that makes us human and healthy.

To illustrate just how impactful our gut bacteria can be on our health, Prof Rob Knight from the University of California San Diego took the bacteria from obese and lean people and transplanted them into the sanitised gut of lab rats and observed the outcome. What happened was that the rats with the gut bacteria from the obese human got fat. And the rats with the lean human bacteria remained lean. Another example is how Helicobacter pylori (H. pylori) bacteria break through the gut defences against stomach acid, resulting in stomach ulcers.

Our gut bacteria have a pivotal role to play in our health. They manufacture vital chemical compounds, protect against diseases, regulate the immune system, and help with digestion. Over the last two decades, scientists have observed the link between gut health and various immune and metabolic functions, autoimmune disorders, and brain and mood disorders. For example, we know that a gut diverse in microbiota promotes health and prevents chronic diseases, whereas poor diversity is a characteristic of obesity, diabetes, asthma, and gut inflammation. Recently, science has begun to figure out that gut health is linked to diseases like multiple sclerosis, inflammatory bowel disease, colon cancer, dementia, Alzheimer's, anxiety, and depression. Research in these areas continues.

The gut has been called the second brain, and for good reason. The enteric nervous system is found in our gut and relies upon the same neurons and neurotransmitters as our central nervous system. A lot of cross-talk goes on between our brain and our gut using this nervous system, but our immune system and hormones also participate in this communication. Due to this communication, the "brain in our gut" plays a key role not only in physical diseases but also in our mental health.

If you have ever felt "butterflies in your stomach", you have experienced this brain-gut connection. It really brings new meaning to having ever had a "gut feeling" about something.

The brain and mental health is a massively complex field, so don't think that gut health is the only cause of diseases impacting these areas. However, as microbiome research progresses, we find that people experiencing anxiety and depression might be helped through dietary changes (using probiotic and non-probiotic foods and supplements) that support the growth and proliferation of the correct type of bacteria. Such steps help to sustain the microorganisms in the gut. These microorganisms help to regulate brain function via the gut-brain axis, impacting functions in the immune system and metabolism by providing essential inflammatory mediators, nutrients, and vitamins. Additionally, poor gut health can contribute to anxiety and other mood disorders because of the gut-brain link. Mental stress can also impact the health of gut bacteria, which also feeds back into the health of the brain-gut axis.

In another surprising finding, researchers have confirmed a link between depression and stomach ulcers. So we know there is a link between gut (H. pylori) bacteria and ulcers, as previously stated, and now also a link between stomach ulcers and depression. Such research absolutely supports the holistic approach to caring for patients with gastrointestinal diseases. Additionally, new research by UQ's Institute for Molecular Bioscience (IMB) and Queensland Brain Institute supports the idea of a feedback loop where gut health impacts brain and mood health and where those undergoing psychotherapy or psychiatric treatment have been observed to exhibit positively-impacted gut symptoms. This could indicate that the mood state can influence gut health as well as gut affecting mood.

Alzheimer's is the most common form of dementia, and the scientific community has long suspected that gut microbiota play a role in developing this disease. Researchers have now shown that the gut bacteria composition in Alzheimer's patients is altered and has reduced microbial diversity. There is also a real correlation between an imbalance in the gut microbiota and the development of amyloid plaque in the brain. Scientists now believe that gut bacteria can influence cerebral functioning, promote neurodegeneration, and modify the immune system's interaction with the nervous system. This is very promising for research into innovative neuroprotective strategies in brain disease treatment.

We all know that not getting enough sleep is detrimental to your health, with many and varied health problems resulting (cardiovascular disease, cancer, Parkinson's disease, autoimmune diseases, and psychological issues such as chronic stress, anxiety, and depression). But did you know that poor sleep can negatively affect your gut microbiome? Researchers have found that those who slept well had a better diversity of gut bacteria, and we know that the more diverse someone's gut bacteria is, the better their overall health. So this finding might indicate that gut microbiome-focused treatment protocols may help reduce the risk or severity of brain diseases and promote a good night's sleep.

One of the most significant things that kills off our internal gut flora is the modern miracle of antibiotics. Ironically, we take them due to illness, only to kill off our good bacteria, which then causes other health problems. Antibiotics can upset your microbiome for more than six months if the good bacteria isn't replaced after taking them. This can cause health effects that may go unnoticed and untreated for a long time until the cause is no longer evident. So, if you're taking antibiotics, make sure you talk to your doctor about it and understand why. They aren't bad; they serve a purpose, but taking antibiotics needs to be followed up with good probiotic replacement therapy if you want to avoid getting gut health-related issues later on.

Besides anti-biotics, eating the wrong foods can also cause gut problems. Food allergies and intolerances, genetics, poor lifestyle choices, chronic stress, and lack of sleep all impact the gut, the brain, and your overall health.

The best way to find out is to have a microbiome test performed by a gut health expert. However, the following symptoms may indicate that you have a gut health issue:

Naturally, if you notice any of these chronic symptoms, you should seek immediately medical attention to ensure you do not have a serious condition. Your gut health has a significant impact on your overall health. As a result, keeping your gut healthy is definitely a priority.

Authors: Miskawaan Health Group (MHG). For further information please visit us online at Miskawaan.com or contact us via: contact@miskawaanhealth.com or call (0)2086 8888.

Series Editor: Christopher F. Bruton, Executive Director, Dataconsult Ltd, chris@dataconsult.co.th. Dataconsults Thailand Regional Forum provides seminars and extensive documentation to update business on future trends in Thailand and in the Mekong Region.

See the rest here:
Alzheimer starts in the gut - Bangkok Post

KYLE HARPER RESPONDS to Monica Greens Review of Plagues Upon the Earth: Disease and the Course of Human History (October 18, 2021):

The history of infectious disease has to be history on a global canvas. Pathogens dont respect political borders, and health inequity is historically inextricable from patterns of wealth and power. Disease is integral to all the big questions of global history questions about long-run economic development, connectivity and encounters, colonialism, and imperialism. The recent review essay by Dr. Monica Green in LARB in response to my history of infectious disease explores the question of how well the book achieves its global intentions. I am grateful for a lengthy review essay from a colleague who shares my enthusiasm for new kinds of genetic evidence, and I appreciate the valuable discussion of how historians can draw from this exciting and rapidly growing source of data. But given the focus of Pasts Imperfect, I would like to continue the discussion of how we might pursue a global history of disease. The review is mostly a missed opportunity in this regard, because it prefers to assert that the book is stilted toward a Western and wealthy perspective. Unfortunately, this criticism rests on a curious and complete refusal to engage the books extensive treatment of non-Western experiences.

To take a representative example, it is claimed that the books effort to periodize the deep history of globalization is Western-focused, because it does not register the dispersal of peoples throughout the Pacific and the Americas as a phase of globalization. The dictionary definition of globalization is the integration of distant societies across space, and historians will forever debate how to configure the processes driving connectivity in the past. But it is unusual to characterize dispersal as a form of integration (and thus as a process of globalization in the conventional meaning). It would be fair enough to argue that we need a different definition of globalization, but it is surprising that the reviewer neglects to mention that two chapters do treat the dispersal of humans over the globe, at great length. A reader of the review would take away the impression that a major theme of the book is simply missing, rather than classified differently than the reviewer would apparently wish.

Unfortunately this omission is not the exception, but rather the rule. To take another example, the review criticizes the books opening vignette, which asks readers to think about some of the daily routines and technologies that many people use to sanitize their bodies and domestic environments. Far from being tone-deaf, the passage begins by asking readers to think about the quotidian experiences familiar to those who are privileged enough to live in a developed society. Moreover, the accusation that such a generic routine is necessarily Western is surely tendentious. After all, in non-Western societies, many people (though of course not all) have access to improved drinking water, toilets, and electricity. To assume that turning on the light switch, using a flush toilet, and washing your hands is the exclusive privilege of Europeans is false (and perhaps a little parochial). But worst of all, it would have only been generous, not to mention responsible, to note that this vignette is followed, immediately, by a stark declaration that the extent of control over infectious disease remains unequal around the globe, as a way of setting up the problem of geographic health disparities as a central theme of the book.

In any case, those instances are reflective of a pattern, which means we have missed an opportunity to ask critical questions about what makes for a good global history of disease. [1] In my view, writing a global history of disease requires an earnest effort to capture as much of the varied human experience as the sources will allow, without navely assuming that any one societys experience was normal. How can this be achieved in practice? In the history of disease, I suggest three strategies:

First, we should widen the infectious diseases that we write about beyond the usual suspects. Smallpox, plague, measles, typhus, tuberculosis, etc., are all canonical, and indeed must be central to the story. But we should recognize that this list leaves out important diseases, many of which are geographically constrained to the tropics and subtropics. In practice, for instance, I have tried to give ample coverage to schistosomiasis, lymphatic filariasis, falciparum malaria, yellow fever, yaws, and trypanosomiasis. All of these afflictions were absent or marginal in Europe, yet hugely important in human history. In general, any book that devotes as much space to these diseases as to the more cosmopolitan ones is probably not egregiously Europe-centered. Regrettably, this coverage is not even mentioned in the lengthy review, so a reader might come away with a mistaken expectation of what is in the book. It represents a missed chance for critical discussion about how expanding the range of diseases could more authentically represent the human experience from a global perspective. Moreover, we will need to take seriously these too-often-neglected tropical diseases to seek out the deep role of geography in human history.

Second, we can decenter narratives of the classic diseases like plague and smallpox, to avoid the misleading impression that somehow the Western experience was paradigmatic. In the case of plague, for instance, both the genetic evidence (as Dr. Green has shown elsewhere) and non-Western written evidence can be tools to revise the traditional narratives. In the case of the Black Death, for instance, we can (and I try to) let the rich Arabic sources have as much space as the European sources. We must also ask hard questions about the impact and timing of plague in China, South Asia, and Africa, too. The history of smallpox is probably more challenging, for now at least, but I have tried to reframe the conventional story of the Columbian Exchange, in which Europeans brought smallpox to the New World with deadly effect in the 16th century, by putting it in a wider, planetary perspective. Smallpox was a bigger problem, everywhere, starting in the 16th century, from Mexico City to Ming China. Sometimes with striking synchronicities, it raged across the planet, from the American Southeast to late Stuart England to early Qing China. In my view, we dont fully understand why this was so, but a global perspective prompts us to question the blinkered model of the virgin-soil epidemics in the New World.

Third, we should try to understand the progress of the last two centuries from a global perspective and not simply a Western triumphalist one, such as is sometimes dominant in the economics literature. Even a global perspective will still need to devote due attention to Europes pioneering role in many facets of public health and biomedicine. But, critically, we should recognize that as modern growth and globalization fueled great health crises (like cholera, the Third Plague Pandemic, and the 1918 influenza), the power dynamics of European imperialism and incipient capitalism meant that health and processes of modernization were deeply entangled, to the disadvantage of many non-Western societies. Rather than seeing modernity as a period of unbroken and continuous triumph, we should try to recognize the complex and sometimes causal relationships between progress and inequity. At the same time, we should also try to offer an honest assessment of the globalization of good health the upward convergence of health outcomes in the 20th century, as developing societies in the age of decolonization rapidly embraced the opportunities to bring infectious diseases under control. One would never guess it from the review, but non-Western experiences of modern development get the majority of the space in the last two chapters of the book.

When you deliberately excise all of the non-Western material, what is left unsurprisingly looks like Western civ. But such selective reading doesnt really advance the cause of global history. Meanwhile, there are genuinely severe challenges in trying to tell the story of infectious disease on a global canvas. Our energy would be better focused on a good-faith discussion of the big methodological and substantive challenges we all face. For instance, the historical demography literature so valuable in trying to understand how people died in the past is wildly skewed toward Europe. So is the paleogenomic evidence, at present. How do we get around these biases in the source material, using what we know from this evidence to make inferences about pre-modern societies, without navely assuming that what we have is actually universally representative? More conceptually, the entanglements of geography, power, and disease are probably among the most complicated questions we can ask about the history of economic development. Economists have been (much) better at helping us understand the causal factors behind improvements in health, but historians have done a better job at treating non-Western experiences and the problem of imperialism. How can we achieve a disciplinary rapprochement? I do not claim to have overcome these problems, only to have confronted them earnestly from a global perspective.

Monica Green Responds to Kyle Harper:

I thank Professor Harper for his detailed reading of my review and his recognition of its call for dialogue on the pressing question of how global health is to be defined and its history pursued in a way that is meaningful for all humanity.

Kyle Harper is professor of classics and letters at the University of Oklahoma.

Monica H. Green is an expert in the history of medicine in premodern Europe and global infectious diseases.

[1] Also notably unhelpful is the insinuation that the simpler terms time travel and tree thinking, used as shorthand for the unwieldly technical terms paleogenomics and phylogenetics, are my cute nicknames. Time travel comes from Svante Pbo and Johannes Krause, two founders of the field, and tree thinking is commonly used as well as the name of one of the standard monographs on how to employ phylogenetic reasoning. In my view, pedantry will not help us as we all work hard to bridge numerous disciplines with their sometimes demanding technical language. Furthermore, I am at a loss to understand how tracking is a third distinct method of using genetics. What is described as tracking in the review is simply phylogenetics (tree thinking) or perhaps its spatial application, phylogeography. I am unfamiliar with specialists in the field who have previously considered this a way of using genetic data entirely apart from phylogenetics.

View post:
Letter to the Editor: Kyle Harper Responds to Monica H. Green - lareviewofbooks

Several studies conducted over the years have found that South Asians have a higher burden of Coronary Artery Disease (PCAD) compared to other ethnicities.

A 2004 INTERHEART study first found that the mean age of the first presentation of heart attack was 53 years, a full10 years ahead of patients from Western Europe, China, Central and Eastern Europe.

Similarly, studies comparing the health of South Asian immigrants show that compared to local populations, they demonstrated a higher burden of CAD.

The INTERHEART study also indicated that South Asians who suffered a heart attack have low HDL-C (good cholesterol) levels, higher triglyceride levels, and a higher particle burden for LDL-C (bad cholesterol) levels.

Also Read |What's wrong with young Indians' hearts?

South Asians also have other risk factors, like dysfunctional HDL levels (where HDL particles lose their antioxidant and anti-inflammatory properties) and Lipoprotein (a) levels.

When asked about the roles of genes in Heart Disease, particularly among the Indian population, Dr Swathi Shetty, Assistant Professor at the Centre for Human Genetics, says the answer is not straightforward.

"If you have a history of heart disease in the family, that could indicate a higher genetic risk than the average population. But because there are so many variables causing heart disease, to pinpoint particular genes is difficult," Dr Swathi says.

CAD, like Cancer, is a multifactorial disease where genetics, environment and lifestyle play a major role. This is in stark contrast to single-gene disorders like Beta Thalassemia, Huntingtons disease or Cystic Fibrosis, where we know the gene associated with the disease.

Also Read |Genetic factors may have led to Puneeth Rajkumars death

"Compared to cancer we are still way behind. We know much more about cancer genes. Cancer is basically the proliferation of cells. It is easier to look at those because we know there are genes which control the division. In Cardiovascular disease (CVD), there are many other factors involved, including the Nitric oxide in your vessels, coagulation factors, and many more,"Dr Swathi says.

For instance, in 2011, 58 genomic regions associated with CAD were discovered, but most of the heritability cannot be explained.

"They have done studies among people with CVDs and looked for areas of DNA that they have in common. And we have found regions that are not even an expressed gene. That is another layer of difficulty. It [gene] doesn't code for a protein. Is it really increasing the risk? For these, we need huge numbers of patients to try and correlate," Dr Swathi adds.

Another 2018 paper studying Premature Coronary Heart Disease burden in South Asians identified six variants of the CX3CR1 gene which were unique to South Asians and "not found in large (mostly European) cohorts".

But the study concluded that findings "do not allow definite conclusions, especially with regard to how these could impact therapy."

While CAD does seem to have a genetic component involved, we also know that lifestyle factors like smoking, exercise, stress management etc also impact development of the disorder, which is something that people can still control and moderate, Dr Swathi adds.

Check out latest DH videos here

Read this article:
Is there a genetic component to heart disease? - Deccan Herald

PHILADELPHIA Penn Medicine has been awarded a $9.5 million grant from The Warren Alpert Foundation (WAF) to continue its efforts to increase diversity in genetic counseling, a field that, despite impressive leaps forward in genetic knowledge, lacks a diverse workforce. The Alliance to Increase Diversity in Genetic Counseling grant will support 40 underrepresented students in five genetic counseling programs in the Northeastern U.S. over five years to expand all dimensions of diversity. The Perelman School of Medicine at the University of Pennsylvanias Master of Science in Genetic Counseling Program will lead this effort, joined by participating Genetic Counseling masters programs at Boston University School of Medicine, Rutgers, The State University of New Jersey, Sarah Lawrence College, and the University of Maryland School of Medicine. Ten students will be selected yearly to receive full tuition support and a cost of living stipend.

The University of Pennsylvania's Master of Science in Genetic Counseling Program (MSGC) and the collaborative programs are committed to increasing diversity and inclusion in the genetic counseling field and encouraging post-graduate training and career advancement opportunities for genetic counselors. Previous philanthropic gifts to the MSGC program have supported a robust summer internship for undergraduates who are underrepresented in Genetic Counseling, which, in its first year, led to two rising juniors and seniors to learn about the field and consider applying to the program. The Class of 2023 is the Penn MSGCs most diverse ever, with 35% of students from underrepresented backgrounds.

"We are honored to receive this grant from The Warren Alpert Foundation to continue to expand diversity and inclusion in genetic counseling while growing the overall genetic counseling workforce," said Daniel J. Rader, MD, Chair of the Department of Genetics in the Perelman School of Medicine and Chief of the Divisions of Human Genetics at both Penn and Childrens Hospital of Philadelphia. The Foundation is extraordinarily forward-thinking in making this generous funding available to address a critical need as the implementation of genomic medicine continues to rapidly expand.

"On the 50th anniversary of genetic counseling being established as a field, we celebrate the first time an alliance of genetic counseling programs has collaborated to increase diversity and inclusion with scholarships, post-graduate training, and career advancements for genetic counselors," said Kathleen Valverde, PhD, LCGC, Program Director of the Penn MSGC.

A key rationale for increasing diversity in the genetic counseling workforce is to improve support for patients from underrepresented backgrounds. The field is currently comprised of 95 percent white females. Therefore, underrepresentation of genetic counselors from diverse backgrounds can strain critical dialogue between genetic counselors and patients, whose health outcomes are often improved through interaction with medical professionals they can relate to more personally. Unless genetic counseling becomes more accessible, existing disparities will be exacerbated. Addressing this issue will require integrated strategies, including expanding genetic research, improving genetic literacy, and enhancing access to genetic technologies and genetic counseling among underrepresented populations in a way that avoids stigmatization and other harms.

"Supporting innovative organizations dedicated to understanding and curing disease through groundbreaking research, scholarship, and service is why we are delighted to award Penn with this generous grant from The Warren Alpert Foundation," said August Schiesser, Executive Director of The Warren Alpert Foundation. "Recruiting and training underrepresented individuals in genetic counseling will increase the numbers of professionals in the field, leading to an increase in access to community-based genetic education and genetic counseling services delivered by individuals who reflect different populations."

"The Penn MSGC program leadership brings extensive experience in genetic counseling education and, with this grant, it will expand its reach to diverse students preparing them to be successful professionals who will advance the field of genetic counseling," said Emma Meagher, MD, a professor of Medicine and Pharmacology, Chief Clinical Research Officer and Associate Dean of Master and Certificate Programs in the Perelman School of Medicine at Penn.

Interested applicants for Penn can visit https://www.med.upenn.edu/geneticcounseling for more information. Application deadlines are as follows: Penn Medicine (Jan. 5, 2022), Boston University School of Medicine (Dec. 15, 2021), Rutgers University (Dec. 18, 2021) Sarah Lawrence College (Dec. 17, 2021), and the University of Maryland School of Medicine (Jan. 10, 2022). Ten students will be selected yearly to receive full tuition support and a cost of living stipend.

The Warren Alpert Foundation AID-GC Program leadership includes Kathleen Berentsen Swenson, MS, MPH, CGC, Director of the Boston University School of Medicine Masters Program in Genetic Counseling; Claire Davis, EdD, CGC, Program Director, and Janelle Villiers, MS, CGC, Assistant Director of the Joan H. Marks Graduate Program in Human Genetics at Sarah Lawrence College; Jessica Rispoli Joines, MS, LCGC, Director of the Genetic Counseling Masters Program at Rutgers University; and Shannan Dixon, MS, CGC, Director of the Masters in Genetic Counseling Training Program at the University of Maryland School of Medicine.

Penn Medicineis one of the worlds leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nations first medical school) and theUniversity of Pennsylvania Health System, which together form a $8.9 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according toU.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $496 million awarded in the 2020 fiscal year.

The University of Pennsylvania Health Systems patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Centerwhich are recognized as one of the nations top Honor Roll hospitals byU.S. News & World ReportChester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nations first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Medicine at Home, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 44,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2020, Penn Medicine provided more than $563 million to benefit our community.

Read this article:
Penn Medicine Awarded $9.5 Million Grant from The Warren Alpert Foundation to Increase Diversity in Genetic Counseling Programs - pennmedicine.org

INDIANAPOLIS When immune cells move throughout the brain, they act as the first line of defense against viruses, toxic materials and damaged neurons, rushing over to clear out them.

Researchers at Indiana University School of Medicine have been investigating how these immune cells in the brainmicrogliarelate to a gene mutation recently found in Alzheimers disease patients. Theypublished their findingstoday in Science Advances.

The study, led byHande Karahan, PhD, postdoctoral fellow in medical and molecular genetics, andJungsu Kim, PhD, the P. Michael Conneally Professor of Medical and Molecular Genetics, found that deleting the genecalled ABI3significantly increased amyloid-beta plaque accumulation in the brain and decreased the amount of microglia around the plaques.

This study can provide further insight into understanding the key functions of microglia contributing to the disease and help identify new therapeutic targets, Karahan said.Karahan based her research on a human genetics study of more than 85,000 peoplefewer than half were Alzheimers patientsthat identified the mutation in the ABI3 gene. Researchers concluded this mutation increased the risk of late-onset Alzheimers.

However, there was no investigation into the function of ABI3 gene in the brain or about how this gene affects microglia function, Karahan said, a fact that led to her research.The team deleted the ABI3 gene from an Alzheimers disease mouse model and tested the functions of the gene in microglia in cell cultures. In the mouse model, they saw increased levels of plaques and inflammation in the brain and signs of synaptic dysfunctioncharacteristics associated with learning and memory deficits of the disease.

Additionally, Karahan said the deletion of the gene impaired the movement of microglia. The immune cells cannot move closer to plaques to try to clear up the proteins. Amyloid plaques are commonly found in the brains of patients with Alzheimers; amyloid beta proteins clump together and form plaques, which destroy nerve cell connections.

Our study provides the first in vivo functional evidence that the loss of ABI3 function may increase the risk of developing Alzheimers disease by affecting amyloid beta accumulation and neuroinflammation, Karahan said.

Over the past few years, Karahan has been building upon her Alzheimers disease research. In 2019, Karahanreceived the Sarah Roush Memorial Fellowship in Alzheimers Disease Research, established by theIndiana Alzheimers Disease Research Centerand funded through a generous donation from James and Nancy Carpenter and a matching contribution fromStark Neurosciences Research Institute, where Karahan conducts her research.

Karahan and Kim received three separate grants supporting this research from the National Institute on Aging, the National Institutes of Health (NIH) branch for Alzheimers research, resulting in $7.8 million over the next five years.

One grant will fund the creation of a mouse model that will allow us to delete the ABI3 gene in any cell types in the body, such as brain microglia and peripheral immune cells, Kim said. Once we validate this new model, we will make it available to others in the research community to use this model for their own investigations.

The other grants will fund additional mouse and cell models for the team to further investigate how the ABI3 gene in microglia affects Alzheimers disease pathologies as well as fund state-of-the-art techniques, including brain imaging using theBruker BioSpec 9.4T PET-MRI scanner, located in the Roberts Translational Imaging Facility at Stark Neurosciences Research Institute.

Each of these projects has an end goal of identifying druggable targets for the treatment of the disease, Karahan and Kim said. The team will collaborate with the IU School of Medicine-Purdue TaRget Enablement to Accelerate Therapy Development for Alzheimers Disease (TREAT-AD) Center.

Deletion of Abi3 gene locus exacerbates neuropathological features of Alzheimers disease in a mouse model of A amyloidosis

3-Nov-2021

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Follow this link:
Researchers investigate role of gene associated with Alzheimer's disease in brain's immune cells Indiana University School of Medicine - EurekAlert

image:Dr. Stephen J. O'Brien (back row, second from left) with orphans in Botswana view more

Credit: Dr. Stephen J. O'Brien

Research Take-a-Ways:

FORT LAUDERDALE/DAVIE, Fla. HIV emerged from African chimpanzee transmission to humans in the first decades of the 20th century. The deadly AIDS disease was first detected among American gay men, hemophiliacs, transfusion blood recipients, and IV drug users sharing needles in the early 1980s. Since then, the rapid world-wide spread of HIV has claimed 37.2 million lives leaving some 38 million people living with HIV infection today.

Today, African AIDS comprises 65-70% of all HIV cases worldwide. In Africa, the HIV-1C strain, which has been suggested as more easily transmitted in heterosexual contact, is predominant. Although AIDS spread and transmission have been reduced by widespread dissemination of anti-retroviral therapies, the horror of AIDS continues, particularly in sub-Saharan Africa.

This study was led by Nova Southeastern University (NSU)Halmos College of Arts and Sciences professor and research scientist Stephen J. OBrien, Ph.D., in collaboration with researchers at the Laboratory of Genomic Diversity at ITMO University, St Petersburg, Russia, Botswana-Harvard AIDS Institute, Gaborone Botswana, T. H. Chan School of Public Health, Harvard University, Boston, and Yale University, New Haven, and St. Petersburg State University.

Epidemiological variation in HIV acquisition, AIDS progression and therapy effectiveness has been attributed, in part, to endemic gene determinates. Studies in the past decades have discovered more than 50 human gene variants that confer relative sensitivity or resistance to AIDS. Nearly all these important studies involved American and European Caucasian patients in spite of the fact that sub-Saharan Africa is the epicenter of AIDS.

In 1996, author Max Essex and the President of Botswana established the Botswana Harvard AIDS Institute Partnership (BHP) in Gaborone Botswana to carry out training , surveillance and treatment of HIV-AIDS patients implementing research Virology, Molecular biology, immunology, genetics and epidemiology

In one of the largest studies to date of African people at risk for HIV infection, a group of 1,173 patients recruited by BHP were sequenced, genotyped, and analyzed to reveal three new common genetic DNA variants that influence whether one becomes infected and in American replication cohort studies the rate and AIDS defining disease by which infected individuals progressed to AIDS.

OBrien and his team have pioneered the field of AIDS Restriction Gene discovery for 25 years, beginning when he led a Research Laboratory at the National Institutes of Health (1986-2012).

The research, published today in the Proceedings of the National Academy of Sciences, revealed three new human genes (AP3B1- Chr-5; PTPRA-chr-20; NEO1-Chr-15) with a marked influence on HIV acquisition. Each gene variant was statistically significant in a Genome Wide Association Study -GWAS of 1.3-8.6 million single nucleotide polymorphism-SNPs.

The new study provides valuable insights into the genetic variants associated with HIV-1C infection and AIDS progression in sub-Saharan Africa, potentially paving the way for new therapies.

Each associated gene has been previously implicated functionally in one or more stages of AIDS pathogenesis and their association was replicated using independent American AIDS cohorts.

A provocative aspect of the AP3B1 variant is that it encodes two alleles G and T, predicting TT, GT and GG genotypes. The Botswana population has a relatively high allele frequency of the G variant (MAF=0.38) relative to other world populations, yet no homozygous GG individuals were detected in Botswana. The GG genotype is also completely absent among 2500 people of all races studied to date, raising the prospect that the AP3B1 -GG genotype may be lethal genotype which does not survive embryogenesis. Further there are several described variants in the in the AP3B1 gene that cause Hermansky-Pudlak syndrome, a rare genetic disease affecting pigmentation and platelets that is sometimes fatal.

The study further describes the replication of 13 previously described AIDS resistance genes using the Botswana population cohort, increasing the confidence in the influence of each. The replication studies were facilitated by the GWATCH ( Genome Wide Association Tracks Chromosome Highway) cyber suite of programs that enhance GWAS data analyses, replication, and release.

Be sure to sign up for NSUs RSS feed so you dont miss any of our news releases, guest editorials and other announcements. Please sign up HERE. You can also follow us on Twitter @NSUNews.

###

About Nova Southeastern University (NSU):At NSU, students dont just get an education, they get the competitive edge they need for real careers, real contributions and real life.A dynamic, private research university, NSU is providing high-quality educational and research programs at the undergraduate, graduate, and professional degree levels. Established in 1964, the university includes 15 colleges, the 215,000-square-foot Center for Collaborative Research, the private JK-12 grade University School, the world-classNSU Art Museum Fort Lauderdale, and theAlvin Sherman Library, Research and Information Technology Center, one of Floridas largest public libraries. NSU students learn at our campuses in Fort Lauderdale, Fort Myers, Jacksonville, Miami, Miramar, Orlando, Palm Beach, and Tampa, Florida, as well as San Juan, Puerto Rico, and online globally.With nearly 200,000 alumni across the globe, the reach of the NSU community is worldwide.Classified as having high research activity by the Carnegie Foundation for the Advancement of Teaching, NSU is one of only 59 universities nationwide to also be awarded Carnegies Community Engagement Classification, and is also the largest private institution in the United States that meets the U.S. Department of Educations criteria as a Hispanic-serving Institution.Please visitwww.nova.edufor more information.

Proceedings of the National Academy of Sciences

People

1-Nov-2021

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

Visit link:
NSU research scientist leads group that discovered gene variants that delimit HIV-1 infection - EurekAlert

Gene linked to doubling the risk of death due to COVID-19 identified using technology exclusively licensed to Nucleome Therapeutics

Study conducted by Nucleomes academic founders at the University of Oxford published in Nature Genetics

Oxford, UK, 5th November 2021 Nucleome Therapeutics, a biotechnology company that is decoding the dark matter of the human genome to uncover novel ways to treat disease, is pleased to note that the Companys academic founders from the University of Oxford have published a paper in Nature Genetics identifying a gene that potentially doubles the risk of death from COVID-19.

The technology used to identify this gene has been exclusively licensed to Nucleome, highlighting the competitive advantage of Nucleomes platform in the discovery of genetic targets for innovative precision medicine development.

Since the start of the pandemic, research teams around the world have been searching for genetic signals in our genome that contribute to the susceptibility and severity of individuals response to COVID-19. Previous work already identified a stretch of DNA on chromosome 3 which doubled the risk of adults under 65 of dying from COVID-19. However, scientists did not know how this genetic signal worked to increase the risk, nor the exact genetic change that was responsible.

Sixty percent of people with South Asian ancestry carry this high-risk genetic signal, compared with one in six people of European ancestry, partly explaining the excess deaths seen in some UK communities and the impact of COVID-19 in the Indian subcontinent.

The researchers used Nucleomes platform, which combines machine learning and novel ultra-resolution 3D genome analysis method to identify the causative genetic variant, the cell types involved and the effector gene, leading them to identify the probable gene responsible, called LZTFL1.

Prof James Davies, Academic Founder of Nucleome Therapeutics and co-lead of the study, said: The genetic signal conferring increased risk was located within what we call the dark matter of the genome. This dark genome regulates cell type-specific gene expression and is still largely uncharted. Using Nucleomes Micro-Capture-C technique we were able to pinpoint the gene. A higher level of LZRFL1 likely prevents the cells lining the airways and the lungs from fighting the virus properly, but importantly it doesnt affect the immune system, so people carrying this version are likely to particularly benefit from vaccination.

Story continues

Dr Danuta Jeziorska, Chief Executive Officer & Founder of Nucleome, said: In addition to shedding light on the biological mechanism of COVID-19, which is of highest importance in the current pandemic, this study also represents significant validation of Nucleomes platform in identifying disease drivers by decoding the genetic variants located in the dark genome. This publication demonstrates that our platform can be applied to cell types and therapeutic areas beyond Nucleomes focus on autoimmune diseases and lymphocytes, opening the door to potential discovery partnerships consistent with our mission of unlocking the dark genome to transform the lives of patients through precision medicine.

The full paper Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locuscan be found here.

End

About Nucleome Therapeutics

Nucleome Therapeutics is decoding the dark matter of the human genome to uncover novel ways to treat disease. The dark genome holds more than 90% of disease-linked genetic variants whose value remains untapped, representing a significant opportunity for drug discovery and development. We have the unique ability to link these variants to gene function and map disease pathways. Our world-leading cell type-specific platform creates ultra-high resolution 3D genome structure maps and enables variant functional validation at scale in primary cell types. This will enable us to discover and develop first-in-class precision medicines. The initial focus of the company is on lymphocytes and related autoimmune disease. Our ambition is to build a robust pipeline of drug assets, with corresponding biomarkers. Nucleome Therapeutics was founded by leading experts in gene regulation from the University of Oxford and backed by investment from Oxford Sciences Enterprises. For more information, please visit http://www.nucleome.com.

Contacts:

Nucleome TherapeuticsDr Danuta Jeziorska, Chief Executive Officer & Foundercontact@nucleome.com

Consilium Strategic CommunicationsSukaina Virji/ Lindsey Neville/ Isobel McLeodnucleome@consilium-comms.com+44 (0)7738 499212

See the rest here:
Gene linked to doubling the risk of death due to COVID-19 identified using technology exclusively licensed to Nucleome Therapeutics - Yahoo Finance

New cutting edge technology recently installed at the Cummings School of Veterinary Medicine at Tufts University reminds Cheryl London, the associate dean for research and graduate education, of the 1966 sci-fi film Fantastic Voyage.

In the movie, an intrepid submarine crew shrinks down small enough to float through an injured scientists bloodstream to save his life.

The new technology, called spatial profiling, allows scientists to see so deep into tissue samples that London, an oncologist, said it feels like youre actually there on the surface of the cell.

Its like taking a birds-eye look inside the cell itself, London said.

The Cummings School won a $2 million grant from the Waltham-based Massachusetts Life Sciences Center for the new equipment this spring, and it was installed over the summer.

London and her team submitted their grant proposal to the MLSC, an organization that pools state and private money to invest in science research across the state, through the agencys Research Infrastructure Program in the fall of 2020.

At the end of February of this year, an email informed London that Tufts had won the competitive grant.

When you get the notification that youve been funded its one of those woo-hoo moments, London said. You do a little dance, and youre pretty excited.

The equipment was installed last June and July in the newly renovated Peabody Pavilion lab space, and by September it was available for use.

The new lab equipment also includes advanced genetic sequencing and NanoString technology, which is able to sequence the DNA of a single cell.

London said the technology is a product of the latest in a series of major scientific leaps in the fields of genomics and pathology and has advanced rapidly.

Spatial profiling technology was only developed in the last five years. Next generation sequencing is slightly older, having been developed in the years following the conclusion of the Human Genome Project in 2003.

This is the first time that either technology will be available on Tufts campus, and the new lab will function as a shared resource, London said. While the technology is currently only available to those who have been trained extensively on how to use the expensive equipment, students and faculty from any of the universitys campuses will be able to submit proposals to use the equipment. London is talking with researchers at Tufts University School of Medicine who intend to apply for funding for experiments that use the technology.

Some research is already underway with the new technology. One of the few researchers who has been using the technology for her research is Heather Gardner (GBS20), a Cummings School assistant research professor specializing in veterinary oncology and genetics.

Gardner studies the impact of losing subsets of genes when DNA is transcribed into RNA in the context of bone cancer. The next generation sequencing has enabled her to examine that process in individual cells, she wrote in an email to the Daily.

The spatial-profiling technology is helping Gardner too. It allows her to zoom in on canine bone cancer micro-environments to examine how the tumors change gene expression.

This equipment really compliments and adds a new dimension to the research already being done, Gardner said.

Frequently, Cummings School researchers like Gardner are doing experiments on nonhuman animal cells not only to develop therapies for the animals themselves, but to use them as models for treatments in humans as well.

For that to work, though, scientists have to ensure the animal models accurately mimic the human body.

Sometimes models look like theyre the real deal on the outside, London said. But when you look at the genetic level its really not the same.

The new technology will help Cummings School researchers do just that.

Joseph Sullivan, vice president of marketing, communications, and community relations at the MLSC, said the organization was very proud to have funded Tufts new equipment.

Sullivan wrote in an email to the Daily that the organization hopes the new shared resources will catalyze scientific collaboration, research and innovation in Worcester and the rest of central Massachusetts with the Cummings School as an anchor institution.

For now, London said the team is still getting [its] feet wet but quickly warming up to the new lab.

Walking in and seeing all of this is super cool, London said. Its like a car enthusiast seeing 10 Lamborghinis in a garage. Its amazing to see the power of the equipment you have around you.

Go here to see the original:
New technology sends Tufts veterinary scientists on journey to center of the cell - Tufts Daily

Breadcrumb Trail Links

Roughly, for every redhead, there are three people with black hair, five with blonde, 15 with light brown and 20 with dark brown, according to a new Canadian study

Author of the article:

A vast survey of nearly 13,000 Canadians of European background has uncovered new clues to the genetic causes of hair colour.

This advertisement has not loaded yet, but your article continues below.

Using data from a massive genetic survey of Canadian volunteers, the study out of University of Toronto at Mississauga identified several possible previously unknown genetic causes for blonde, red and light or dark brown hair. It also offers a good estimate of how those colours are distributed among white Canadians.

Roughly, for every redhead, there are three people with black hair, five with blonde, 15 with light brown and 20 with dark brown, according to the studys findings.

These colours are what geneticists refer to as phenotypes, the observable or measurable characteristics of an organism, such as a human being. Most phenotypes are determined by the interaction of an organisms genotype, its set of genes, with the environment and experience.

This advertisement has not loaded yet, but your article continues below.

But hair colour is curious. It is a genetically controlled expression of pigmentation, like eye colour and skin colour with which it correlates, and one of the few complex human traits that is largely unaffected by a persons environment.

Hair colour arises from differences in the amount and ratio of melanins in the hair bulb, from which the strand grows. This is a process that is controlled by genetics and has been affected by many different evolutionary factors. The genes that are known to control it, however, do not seem to do so directly, more by regulating other genes.

We know from recent studies that there are hundreds of variants in many genes involved in this, but sometimes just knowing the gene is not enough information because within one gene you can have mutation, what we call variants, said lead author Frida Lona-Durazo, who recently completed doctoral research on the biology of hair, skin and eye pigmentation in the Department of Anthropology at the University of Toronto at Mississauga.

This advertisement has not loaded yet, but your article continues below.

Our objective was to pinpoint which variants are responsible, even if we know already some genes.

The researchers did not discover any previously unknown genes, but they were able to pinpoint other variants in or near genes that have not been described before, Lona-Durazo said in an interview.

To do this, she and colleagues looked at many complex areas of the human genome that are known to change a persons hair colour, seeking correlation with self-declared hair colour.

The research focused on people of European background because they show the greatest variation in hair colour. Asian and African populations show variation in hair colour, but the range is narrower, and it is harder to study as a self-reported variable. Ideally, Lona-Durazo said, research could be done on all populations by measuring melanin levels objectively in the lab, rather than asking subjects to report their own hair colour.

This advertisement has not loaded yet, but your article continues below.

Participants in the new Canadian study were asked to self-report their natural hair colour as falling into one of the five colour categories offered, or to answer not applicable. The question specified that this was about hair colour before greying, in which pigmentation declines normally with age.

The data showed interesting regional variations. The proportion of people with black hair from Quebec was much higher than British Columbia, and the proportion of people with red hair from B.C. was much higher than Quebec. Ontario and Albertas proportions were very similar, whereas the Atlantic provinces had proportionally more black and dark brown hair and less blonde.

There was a slight sex bias in the number of participants, with about 54 per cent female. But roughly two thirds of people who describe their hair as black were male. All other colour categories were more evenly balanced, male to female. One possible reason for this, according to Lona-Durazo, is a bias among men to say they have black hair and/or a bias among women to say they do not. Another possible factor is that females in general tend to have lighter skin pigmentation, which is correlated with hair colour.

This advertisement has not loaded yet, but your article continues below.

Variation in hair colour is correlated with variation in eye and skin colour, though not perfectly. Some people with blonde hair have blue eyes, for example, but not all all of them. Also, the global variation in skin pigmentation shows a clear pattern that suggests it is an adaptation to ultraviolet radiation. Hair colour is not so obvious.

Current evidence indicates that there is a partial overlap in the genetic architecture of hair, eye and skin pigmentation, according to the paper newly published in Communications Biology.

Much of the interest, beyond pure science, is the application of this knowledge about pigmentation genetics to the understanding of skin cancers. Several genes associated with pigmentation are known to increase melanoma risk, for example.

This advertisement has not loaded yet, but your article continues below.

This genome-wide meta analyses of hair colour among 12,741 Canadians of European background was made possible by the Canadian Partnership For Tomorrows Health, known as CanPath. Using data collected from volunteers, the studys purpose is to offer health researchers around the world comprehensive genomic, clinical, behavioural and environmental data on 330,000 Canadians.

A similar project in Britain in 2018 noted that natural hair colour within European populations is strikingly variable. It found more than 200 genetic variants independently associated with multiple hair colours on the spectrum of blond to black, and learned that many of those genes are involved in hair growth and texture, not pigmentation. The authors suggested that perceived hair colour in fact arises from the complex interaction of pigmentation and shape, because of different refractive and reflective properties. Strands of blonde hair, for example, tend to be thinner than darker hair.

Curiously, the British study also found the male bias toward black hair, but it also found females were more likely to report blonde or red hair. The Canadian numbers do not seem to show this.

This advertisement has not loaded yet, but your article continues below.

This advertisement has not loaded yet, but your article continues below.

Sign up to receive the daily top stories from the National Post, a division of Postmedia Network Inc.

A welcome email is on its way. If you don't see it, please check your junk folder.

The next issue of NP Posted will soon be in your inbox.

We encountered an issue signing you up. Please try again

Postmedia is committed to maintaining a lively but civil forum for discussion and encourage all readers to share their views on our articles. Comments may take up to an hour for moderation before appearing on the site. We ask you to keep your comments relevant and respectful. We have enabled email notificationsyou will now receive an email if you receive a reply to your comment, there is an update to a comment thread you follow or if a user you follow comments. Visit our Community Guidelines for more information and details on how to adjust your email settings.

Follow this link:
Hair colour: Maybe we're born with it. Maybe it's a melanin gene - National Post

An estimated three-quarters of Texans have COVID-19 antibodies, either due to natural infection or from a vaccine.

HOUSTON It's estimated that over 75% of Texans have the antibodies that fight COVID-19, according to a survey done by public health experts with Texas CARES.

The survey also determined that on average, COVID-19 antibody levels peak about 120 days after someone's infected and may return to undetectable levels as early as 275 to 500 days following the virus' infection.

Additionally, experts say those who are not vaccinated and were previously infected with COVID-19 have a lower number of antibodies compared with fully vaccinated survey participants.

Texas CARES data revealed to us that fully vaccinated participants showed significantly higher antibody levels than those with a natural infection only, said Eric Boerwinkle, PhD, dean, M. David Low Chair in Public Health, and Kozmetsky Family Chair in Human Genetics at UTHealth School of Public Health. This suggests to us that vaccination may provide the highest level of protection, even for those who have had a prior COVID-19 infection and developed antibodies.

Nearly 4,000 children ages 5 to 19 enrolled in a COVID-19 seroprevalence survey and the data revealed more than 33% who participated have antibodies to the virus, and of those, 50.8% were asymptomatic. Nearly half, 44.9%, of parents reported the pandemic impacted their childs mental health negatively.

How was the survey done?

Participants were asked to complete a brief survey about their health and were then instructed to visit a participating clinic to have their blood drawn for three antibody tests administered several months apart. This allowed the survey team to measure antibody levels over a longer period of time and understand how long immune protection from natural infection and vaccination may last.

We are so thankful for all the Texans who volunteered to be in our survey, said Jennifer Shuford, MD, MPH, Chief State Epidemiologist with DSHS. We now have a better understanding of antibody levels in a diverse group of Texans with different experiences. Texas CARES participants are helping us understand the dynamics of the pandemic and what we can do to end it. And were not done yet.

Texas CARES is composed of a team of health experts from the University of Texas Health Science Center at Houston (UTHealth Houston) and is funded by the Texas Department of State Health Services (DSHS).

The rest is here:
More than 75% of Texans have COVID-19 antibodies, survey says - KHOU.com