Category Archives: Genetics

COVID-19 is a respiratory disease caused by an infection with the coronavirus SARS-CoV-2.

Since its discovery in late 2019, the coronavirus has led to more than 6.45 million deaths worldwide and more than 1 million deaths in the United States.

COVID-19 can lead to severe or life threatening illness, especially in older adults, people who are not vaccinated, and people with weakened immune systems. Most people with COVID-19 develop mild symptoms.

Loss of smell or taste are two of the most-reported symptoms. Other common symptoms of COVID-19 include:

Research suggests that people with certain genes may develop loss of taste or smell more often. Scientists are continuing to examine this association. Read on to learn what we know so far about the link.

Loss of smell and loss of taste are commonly reported COVID-19 symptoms. Researchers are continuing to examine why some people with COVID-19 develop these symptoms while others dont. Recent evidence suggests genetics may play a role.

Among 32,142 people with COVID-19 in a 2021 review of studies, 38.2% of them developed loss of smell while 36.6% developed loss of taste.

In a 2022 study, researchers collected data on COVID-19-related loss of smell or taste from surveys from 69,841 people. Researchers found that 68% of people reported one of these symptoms.

Researchers found that certain location variants of the UGT2A1 and UGT2A2 genes expressed in the olfactory epithelium were associated with COVID-19-related loss of smell. Your olfactory epithelium is a thin layer of tissue along the roof of your nose that helps you smell.

These two genes play a role in metabolizing substances called odorants that trigger your sense of smell. But its not clear exactly how and why these genes influence COVID-19-related smell loss.

Several possible reasons people with COVID-19 develop loss of smell have been hypothesized, but the exact cause isnt clear. Possible mechanisms theorized to contribute include:

Experimental evidence suggests damage to the cilia in your nose and olfactory epithelium contribute to loss of smell in people with COVID-19, but not infection of the nerves in your brain that help you smell. Cilia are tiny hairs that help clear away mucus.

This evidence also suggests the coronavirus enters and accumulates in olfactory support cells through angiotensin converting enzyme 2 and transmembrane protease serine 2. Dysfunction of these cells can impair your ability to smell.

In a 2021 review of 45 studies including 42,120 people with COVID-19, researchers found that people severely ill or hospitalized for COVID-19 had a lower chance of experiencing loss of smell than those who were not severely ill or hospitalized.

In the 2022 study mentioned above, researchers found:

Learn more about who is most likely to lose their sense of smell and taste.

In a 2021 study involving 67 people with COVID-19, 74.6% recovered their sense of smell an average of 60 days after developing COVID-19. The remaining 25.4% had persistent smell loss that lingered beyond 60 days.

Another 2021 study found that 96.1% of a group of 97 people with COVID-19-related loss of smell recovered by 12 months, which was about 10% more than had recovered at 6 months.

In a 2021 review of 17 studies, researchers found that the average duration of smell and taste disorders was 7.5 days, plus or minus 3.2 days, in a group of 79 people with COVID-19. Meanwhile, 40% of people recovered completely within 7.4 days, plus or minus 2.3 days.

Learn more about how long people with COVID-19 lose their sense of smell.

Most people regain their sense of smell or taste within a couple of months of developing COVID-19. However, a small number of people have lingering effects that can last for a year or longer.

If your smell doesnt return, your doctor may recommend olfactory training.

Olfactory training involves repeatedly sniffing scents for 20 seconds each at least twice a day for 3 months or more. Common scents include lemon, rose, cloves, and eucalyptus.

Research suggests that olfactory training can be an effective treatment for COVID-19-related smell loss.

Some doctors may recommend treatments like steroids and high doses of omega-3 fatty acids. These have been found to be effective for treating smell loss from nonviral causes.

One small 2020 study found evidence that omega-3s helped protect the sense of smell in people undergoing nasal surgery. The ability of omega-3s to treat COVID-19-related smell loss remains theoretical.

Additionally, intranasal vitamin A has also been recommended as a possible therapy that may help with olfactory regrowth.

Visit your doctor if you or your child have lingering symptoms that persist about 4 weeks or longer after you develop COVID-19.

Your doctor can suggest tests that may identify the root cause of your symptoms and rule out other conditions that may be contributing.

Loss of taste and smell are commonly reported symptoms of COVID-19. Researchers are still trying to understand why some people develop these symptoms and others dont. Current evidence suggests genetics may contribute.

In particular, researchers have identified UGT2A1 and UGT2A2 as genes linked to COVID-19-related smell loss. More research is needed to understand exactly what role these genes play.

More here:
Is COVID-19 Loss of Smell Genetic? What Research Shows - Healthline

SAN DIEGO If living into your 90s seems to run in the family, dont just assume that means you will too.Our genetics make us who we are, but new research from the University of California, San Diego finds exercise trumps genes when it comes to promoting a longer life.

You dont need a medical degree to know that forgoing physical activity in favor of stagnation isnt the wisest choice for your health and longevity. But, certain people are genetically predisposed to live longer than others. The research team at UCSD set out to determine if such individuals dont have to move quite as much as the rest of us to live just as long.

The goal of this research was to understand whether associations between physical activity and sedentary time with death varied based on different levels of genetic predisposition for longevity, says lead study author Alexander Posis, M.P.H., a fourth-year doctoral student in the San Diego State University/UC San Diego Joint Doctoral Program in Public Health, in a university release.

This research project began a decade ago. In 2012, as part of the Womens Health Initiative Objective Physical Activity and Cardiovascular Health study (OPACH), study authors began keeping track of the physical activity habits among 5,446 older U.S. women (ages 63 or older). Subjects were tracked up until 2020, and wore a research-grade accelerometer for up to seven days. That device measured how much time they spent moving, the intensity of that physical activity, and their usual amount of sedentary time.

Sure enough, higher levels of light physical activity and moderate-to-vigorous physical activity were associated with a lower risk of dying during the tracking period. Additionally, more time spent sedentary was associated with a higher risk of mortality. Importantly, this observed connection between exercise and a longer life remained consistent even among women determined to have different levels of genetic predisposition for longevity.

Our study showed that, even if you arent likely to live long based on your genes, you can still extend your lifespan by engaging in positive lifestyle behaviors such as regular exercise and sitting less, explains senior study author Aladdin H. Shadyab, Ph.D., assistant professor at the Herbert Wertheim School of Public Health and Human Longevity Science at UC San Diego. Conversely, even if your genes predispose you to a long life, remaining physically active is still important to achieve longevity.

In conclusion, study authors recommend that older women engage in physical activity of any intensity as regularly as possible. Doing so will lower the risk of both various diseases and premature death.

The study is published in the Journal of Aging and Physical Activity.

Read more:
You're in control: Exercise outweighs genetics when it comes to longer life - Study Finds

Armed with a 30 million grant from the British Heart Foundation, an international team of researchers from the UK, US, and Singapore is setting their sights on curing forms of genetic heart disease using gene therapy.

Called the CureHeart Project, the team which includes researchers from Oxford, Harvard, Singapores National Heart Research Institute, and pharma multinational Bristol Myers Squibb will develop therapies for inherited heart muscle conditions, which impact millions and can cause sudden death, including in young people.

They plan to tackle the problem using two types of targeted techniques, called base editing and prime editing.

An international team of researchers wants to develop a one-shot cure for inherited heart muscle conditions.

Many of the mutations seen in these patients come down to one fateful letter in their DNA code, Christine Seidman, professor of medicine and genetics at Harvard Medical School and co-lead of CureHeart, told The Guardian.

That has raised the possibility that we could alter that one single letter and restore the code so that it is now making a normal gene, with normal function, Seidman said.

The teams work is building on successful demonstrations in animals.

Our goals are to fix the hearts, to stabilise them where they are and perhaps to revert them back to more normal function, Seidman said.

Fixing genetic heart disease: Inherited heart muscle diseases cause abnormalities in the heart, which are passed on through families.

Many different mutations can cause them, but in total, they affect one out of every 250 people around the world, Hugh Watkins, CureHearts lead investigator and the director of Oxfords British Heart Foundation Centre of Research Excellence, told The Guardian.

People of any age can fall victim to sudden heart failure and death, and there is generally a 50/50 chance of passing the problem along to their children.

But decades of genetic research and recent innovations in gene therapy have researchers believing that gene editing may be the answer and even, eventually, the cure.

After 30 years of research, we have discovered many of the genes and specific genetic faults responsible for different cardiomyopathies, and how they work, Watkins said.

Inherited heart muscle conditions impact millions of people, and can cause sudden death.

By using prime and base editing very precise tools for editing DNA the team hopes to develop an injectable cure to repair faulty heart genes, the British Heart Foundation said in a release.

We believe that we will have a gene therapy ready to start testing in clinical trials in the next five years, Watkins told The Guardian.

According to CureHeart, their genetic goals are twofold.

When the cause is a fault in one copy of a gene, which stops the healthy copy from working, they want to switch off the faulty copy; their second approach will be to edit the broken gene sequence itself, to correct it. Theyve demonstrated both methods in mouse models.

Delivering cures: To achieve those goals, the team is turning to two different precision gene editing techniques: prime editing and base editing.

Both enable researchers to edit DNA strands without completely slicing through them (unlike the earlier CRISPR techniques). Prime editing allows researchers to insert or remove certain parts of the genome more precisely, with less collateral damage and fewer errors.

Prime editors offer more targeting flexibility and greater editing precision, Broad Institute chemist David Liu told Science.

They plan to tackle the problem using two types of targeted genetic techniques, called base editing and prime editing.

Base editing which, Science reported, Lius lab invented involves even smaller edits, engineering single letters in the code.

We may be able to deliver these therapies in advance of disease, in individuals we know from genetic testing are at extraordinary risk of having disease development and progressing to heart failure, Seidman told The Guardian.

Never before have we been able to deliver cures, and that is what our project is about. We know we can do it and we aim to get started.

Wed love to hear from you! If you have a comment about this article or if you have a tip for a future Freethink story, please email us at [emailprotected]

Visit link:
An international team sets out to cure genetic heart diseases with one shot - Freethink

Evolution has long been thought to be random, however, a recent study suggests differently.

Evolution has long been thought of as a relatively random process, with species features being formed by random mutations and environmental factors and thus largely unpredictable.

But an international team of scientists headed by researchers from Yale University and Columbia University discovered that a specific plant lineage independently developed three similar leaf types repeatedly in mountainous places scattered across the Neotropics.

The research revealed the first examples in plants of replicated radiation, which is the repeated development of similar forms in different regions. This discovery raises the possibility that evolution is not necessarily such a random process and can be anticipated.

The study was recently published in the journal Nature Ecology & Evolution.

Similar leaf types evolved independently in three species of plants found in cloud forests of Oaxaca, Mexico, and three species of plants in a similar environment in Chiapas, Mexico. This example of parallel evolution is one of several found by Yale-led scientists and suggests that evolution may be predictable. Credit: Yale University

The findings demonstrate how predictable evolution can actually be, with organismal development and natural selection combining to produce the same forms again and again under certain circumstances, said Yales Michael Donoghue, Sterling Professor Emeritus of Ecology & Evolutionary Biology and co-corresponding author. Maybe evolutionary biology can become much more of a predictive science than we ever imagined in the past.

The research team examinedthe genetics and morphology of the Viburnum plant lineage, a genus of flowering plants that started to spread into Central and South America from Mexico around 10 million years ago. Donoghue conducted research on this plant group for his Ph.D. dissertation at Harvard 40 years ago. At the time, he advocated an alternate theory according to which large, hair-covered leaves and small, smooth leaves both evolved early in the history of the group and later migrated separately, being scattered by birds, through the different mountain ranges.

However, the new genetic analyses presented in the study demonstrate that the 2 different leaf types evolved separately and simultaneously in each of many mountain regions.

I came to the wrong conclusion because I lacked the relevant genomic data back in the 1970s, Donoghue said.

The team found that a very similar set of leaf types evolved in nine of the 11 regions studied. However, the full array of leaf types may have yet to evolve in places where Viburnum has only more recently migrated. For instance, the mountains of Bolivia lack the large hairy leaf types found in other wetter areas with little sunshine in the cloud forest in Mexico, Central America, and northern South America.

These plants arrived in Bolivia less than a million years ago, so we predict that the large, hairy leaf form will eventually evolve in Bolivia as well, Donoghue said.

Several examples of replicated radiation have been found in animals, such as Anolis lizards in the Caribbean. In that case, the same set of body forms, or ectomorphs, evolved independently on several different islands. With a plant example now in hand, evolutionary biologists will try to discover the general circumstances under which solid predictions can be made about evolutionary trajectories.

This collaborative work, spanning decades, has revealed a wonderful new system to study evolutionary adaptation, said Ericka Edwards, professor of ecology and evolutionary biology at Yale and co-corresponding author of the paper. Now that we have established the pattern, our next challenges are to better understand the functional significance of these leaf types and the underlying genetic architecture that enables their repeated emergence.

Reference: Replicated radiation of a plant clade along a cloud forest archipelago by Michael J. Donoghue, Deren A. R. Eaton, Carlos A. Maya-Lastra, Michael J. Landis, Patrick W. Sweeney, Mark E. Olson, N. Ival Cacho, Morgan K. Moeglein, Jordan R. Gardner, Nora M. Heaphy, Matiss Castorena, Al Segovia Rivas, Wendy L. Clement, and Erika J. Edwards, 18 July 2022, Nature Ecology & Evolution.DOI: 10.1038/s41559-022-01823-x

View post:
Yale Study Suggests That Evolution Can Be Predicted - SciTechDaily

Where some people see race, gender, and ZIP code as drivers of cancer risk, Olufunmilayo (Funmi) I. Olopade, MD, also sees DNA, RNA, and alleles the stuff of genes and genetic ancestry.

Dr. Olopades work revolves around the intersection of genetics, breast cancer, and racial health disparities. Her research on aggressive breast cancers in young Black African and Black American women has revealed variants of genetic mutations that raise risk for breast cancer and link these two communities.

The Walter L. Palmer Distinguished Service Professor of Medicine and Human Genetics and director of the Center for Clinical Cancer Genetics and Global Health at the University of Chicago Medicine, Olopade earner her MD from the University of Ibadan in Nigeria in 1980. She joined the University of Chicago faculty in 1986.

Her work on cancer risk assessment, prevention, and treatment garnered the Distinguished Clinical Scientist Award of the Doris Duke Charitable Foundation in 2000, a MacArthur Genius Fellowship in 2005, and the 2017 Mendel Medal Lecture at Villanova University.

Today, Olopade continues to build on her work by showing other researchers and clinicians how to explore ancestry-specific genetic variants that lead to breast cancer, and how to use that knowledge to tailor prevention efforts and treatment to each persons needs.

As part of Closing the Cancer Gap, a continuing series on cancer disparities, the world-renowned expert explains her quest to harness heredity and realize the promise of precision medicine for everyone, whether in Nigeria or on the South Side of Chicago.

This interview has been edited for length and clarity.

Everyday Health:You were the first person to link a mutation in the BRCA gene, known to increase risk for breast cancer, in Nigerian women to BRCA mutations in Black American women of African descent. What led to that revelation?

Olufunmilayo I. Olopade:Originally, I wasnt focused on breast cancer. I was in Chicago studying genetics and looking at lymphoma (cancer of the lymphatic system). But then I saw so many young African American women seeking bone marrow transplants because they were facing advanced breast cancers. Some were only in their twenties and came from families with a history of the disease.

I began to seek out the stories of these young women and of others, including the namesake of the Susan G. Komen Foundation (a leading organization funding breast cancer research and awareness globally). Her personal journey and those of the many women who helped the disease gain visibility were intriguing.

Then I went back to Africa and saw young women crowded into a hospital waiting room, desperately sick with advanced breast cancers. I wondered whether we could link our knowledge about the genetic basis of the aggressive breast cancers in American women to these women from Africa and of African ancestry. I felt there was an imperative here, because these fast-growing cancers, called triple-negative, contribute to a 41 percent greater risk of African American women dying from breast cancer compared with their white counterparts.

Ten to 20 percent of all breast cancers in the United States are triple-negative. These cancers are harder to control because they lack the three most common hormone receptors (proteins inside and on the surface of cells that receive messages telling cells what to do). Since many breast cancer therapies target those three receptors, we must look at other options when treating cases of triple-negative.

EH: So, the triple-negative work propelled you into studying breast cancer and genetic ancestry?

OIO: After I launched the University of Chicago Cancer Risk Clinic in 1992, my team and I spent years studying genetics and learning how to identify women at the highest risk of breast cancer. We gathered findings from a large geographical area of Africa and compared them with results found in African Americans in Chicago.

Thats how we confirmed that this specific kind of breast cancer, which shared recurrent BRCA1 (breast cancer 1) mutations, existed in extended African American families with histories of breast cancer and in Africans.

As we continued to grow our knowledge about genetics, we marked the 30th anniversary of the clinics founding in July 2022 with a name change, from the Cancer Risk Clinic to the Cancer Prevention Clinic.

The switch reflects our move beyond fundamental biology understanding how the disease works to using genetics to allow early preventive measures, while, hopefully, maintaining a focus on equity in the medical system. By that I mean ensuring that underserved and underrepresented communities are part of our studies and clinical trials, and that they have access to the genetic screening and counseling too often denied them.

EH: The American Association for Cancer Research 2022 Disparities Report notes that breast cancer is the most prevalent form of cancer among Black American women and predicts that 36,260 new cases will be diagnosed in 2022. Since BRCA genes are relatively rare, what other factors may be contributing to the large case numbers?

OIO:One of the main causes was apparent almost immediately when I first came to Chicago; the presence of two cities.

When I arrived from Nigeria in 1986, I couldnt believe the level of segregation. There were food deserts and medical deserts and insufficiencies in the health system in some South Side and West Side neighborhoods with predominantly African American residents.

There were so few pharmacists in some areas that people couldnt get the medications they needed and would run out. And the health infrastructure was so deficient that it was extremely difficult for the most vulnerable Chicagoans to stay healthy. To my surprise, this was happening in the most well-resourced and blessed country in the world.

Olufunmilayo I. Olopade, MD

Our team was able to bring in many of these people for screening. But if they needed follow-up and treatment, it became tough for them. Many had to drop out because of other issues a lack of transportation, for example, no time off for medical appointments, being a family members caregiver, as well as their inability to pay or a lack of insurance.

Unfortunately, the healthcare system is now reckoning with the general inattention to diseases that affect certain populations. Society has fragmented us into healthcare haves and have-nots.

EH: How can we improve the outcomes for underserved communities while benefiting everyone?

OIO: We have to find a way to get genetic testing done for everyone so that we can fully understand individuals risks and respond accordingly. And when someone has a greater chance of developing the disease, we need to find a way to secure a breast MRI (magnetic resonance imaging), which can pick up cancer long before a mammogram can.

Assessing risk can also help us determine whether we can and should use one of the three approved drugs shown effective in clinical trials at reducing cancer risk. Some of the answers may come from a study now underway, called the WISDOM project (Women Informed to Screen Depending on Measures of Risk), which compares the effectiveness of two approved screening approaches: annual mammograms starting at age 40 for all women versus creating a personalized risk profile and screening program.

EH: What else may be keeping us from making better progress?

OIO:If we could evaluate everyones genetic profile, we could catch the disease as early as possible instead of waiting for people to become ill. Any cancer is potentially curable if discovered early enough.

But right now, too many people dont know that genetic tests are available, too few doctors ask for them, and insurance often denies coverage. Without solving those problems, we cant take full advantage of the power of precision medicine.

EH: What do you mean by precision medicine?

OIO:Im referring to the ability to select the right drug for the right condition at the right time. Using the appropriate treatment when its most effective can help prevent and treat cancers with fewer side effects.

Genetic information enables us to determine who needs chemotherapy, which type is most effective, and when immunotherapy, for example, is more effective. Not all very early cancers are deadly. Some can be closely watched. Some need additional intervention or require a different kind of prevention.

In the next decade, I predict well see this kind of optimized treatment become available for everyone, whether in Nigeria or on the South Side of Chicago. We will make it all happen.

EH: What drew you to the field of medicine?

OIO: My father was a pastor, so when people were sick, they would come to our house for prayers. Some, of course, remained ill, and my father whose unofficial motto was health is wealth would always remark about how wonderful it would be to have a doctor in the family; someone who could provide more help to these people. He strongly encouraged me to learn about medicine.

Olufunmilayo I. Olopade, MD

Although Im the only one of six siblings who became a doctor, I have a sister whos a nurse and a daughter, one of my three children, runs a healthcare company, Cancer IQ, that has created an application to help medical providers track critical genetic information.

EH: What are your current projects and goals?

OIO: Were trying to develop better ways to assess breast cancer risk, particularly through the use of image-based biomarkers in breast MRIs.

We did a study, published in the March 2019 issue of Clinical Cancer Research, showing that scheduling two MRIs a year is preferable to a single yearly mammogram for younger women at high risk for some forms of breast cancer. But MRIs are more expensive than mammograms. And, as I said before, insurance doesnt always cover them.

When I refer to biomarkers, Im suggesting that we have the ability to do extremely accurate assessments using artificial intelligence, which can read millions of MRI images and pick out subtle changes that mammograms cant. So, from the very first screening, we can monitor these women and plan for any potential interventions, if and when they become necessary.

We also want to better understand why certain populations have much lower levels of breast cancer. Individuals of Asian or Hispanic descent, who are less prone to develop certain breast cancers, may help us pinpoint and isolate whatever particular protective factor is involved. That could potentially lead to future preventions and treatments.

And, of course, I also plan to maintain our focus on equity in access, as we continue to study the effects of new drugs on women of African descent and on the entire population. We need to ensure that we fully understand the side effects on the entire range of people taking these drugs.

Premature breast cancer death is unacceptable; too many women die too young. So, our current goal is the same as always: identify the patient, predict the risk, and prevent the cancer.

EH: Whats the most challenging part of your work?

OIO: The toughest thing you face as a doctor is losing a patient. I try to remember that there is great value in creating an end-of-life plan that diminishes pain and suffering and preserves true dignity. As doctors, we have moments of victory and moments when we are humbled by what we do, but to be present with a patient at the end is so important.

Originally posted here:
Olufunmilayo I. Olopade, MD: Cutting Into Breast Cancer Disparities With Genetic Testing - Everyday Health

Last Christmas, as the Omicron variant was ricocheting around the United States, Mary Carrington unknowingly found herself at a superspreader eventan indoor party, packed with more than 20 people, at least one of whom ended up transmitting the virus to most of the gatherings guests.

After two years of avoiding the coronavirus, Carrington felt sure that her time had come: Shed been holding her great-niece, who tested positive soon after, and she was giving me kisses, Carrington told me. But she never caught the bug. And I just thought, Wow, I might really be resistant here. She wasnt thinking about immunity, which she had thanks to multiple doses of a COVID vaccine. Rather, perhaps via some inborn genetic quirk, her cells had found a way to naturally repel the pathogens assaults instead.

Carrington, of all people, understood what that would mean. An expert in immunogenetics at the National Cancer Institute, she was one of several scientists who, beginning in the 1990s, helped uncover a mutation that makes it impossible for most strains of HIV to enter human cells, rendering certain people essentially impervious to the pathogens effects. Maybe something analogous could be safeguarding some rare individuals from SARS-CoV-2 as well.

Read: America is running out of COVID virgins

The idea of coronaviral resistance is beguiling enough that scientists around the world are now scouring peoples genomes for any hint that it exists. If it does, they could use that knowledge to understand whom the virus most affects, or leverage it to develop better COVID-taming drugs. For individuals who have yet to catch the contagiona fast-dwindling proportion of the populationresistance dangles like a superpower that people cant help but think they must have, says Paula Cannon, a geneticist and virologist at the University of Southern California.

As with any superpower, though, bona fide resistance to SARS-CoV-2 infection would likely be very rare, says Helen Su, an immunologist at the National Institutes of Allergy and Infectious Disease. Carringtons original hunch, for one, eventually proved wrong: She recently returned from a trip to Switzerland and found herself entwined with the virus at last. Like most people who remained unscathed until recently, Carrington had done so for two and a half years through a probable combination of vaccination, cautious behavior, socioeconomic privilege, and luck. Its entirely possible that inborn coronavirus resistance may not even existor that it may come with such enormous costs that its not worth the protection it theoretically affords.

Of the 1,400 or so viruses, bacteria, parasites, and fungi known to cause disease in humans, Jean-Laurent Casanova, a geneticist and an immunologist at Rockefeller University, is certain of only three that can be shut out by bodies with one-off genetic tweaks: HIV, norovirus, and a malaria parasite.

The HIV-blocking mutation is maybe the most famous. About three decades ago, researchers, Carrington among them, began looking into a small number of people who we felt almost certainly had been exposed to the virus multiple times, and almost certainly should have been infected, and yet had not, she told me. Their superpower was simple: They lacked functional copies of a gene called CCR5, which builds a cell-surface protein that HIV needs in order to hack its way into T cells, the viruss preferred human prey. Just 1 percent of people of European descent harbor this mutation, called CCR5-32, in two copies; in other populations, the trait is rarer still. Even so, researchers have leveraged its discovery to cook up a powerful class of antiretroviral drugs, and purged the virus from two people with the help of 32-based bone-marrow transplantsthe closest that medicine has come to developing a functional HIV cure.

The stories with those two other pathogens are similar. Genetic errors in a gene called FUT2, which pastes sugars onto the outsides of gut cells, can render people resistant to norovirus; a genomic tweak erases a protein called Duffy from the walls of red blood cells, stopping Plasmodium vivax, one of several parasites that causes malaria, from wresting its way inside. The Duffy mutation, which affects a gene called DARC/ACKR1, is so common in parts of sub-Saharan Africa that those regions have driven rates of P. vivax infection way down.

In recent years, as genetic technologies have advanced, researchers have begun to investigate a handful of other infection-resistance mutations against other pathogens, among them hepatitis B virus and rotavirus. But the links are tough to definitively nail down, thanks to the number of people these sorts of studies must enroll, and to the thorniness of defining and detecting infection at all; the case with SARS-CoV-2 will likely be the same. For months, Casanova and a global team of collaborators have been in contact with thousands of people from around the world who believe they harbor resistance to the coronavirus in their genes. The best candidates have had intense exposures to the virussay, via a symptomatic person in their homeand continuously tested negative for both the pathogen and immune responses to it. But respiratory transmission is often muddied by pure chance; the coronavirus can infiltrate people silently, and doesnt always leave antibodies behind. (The team will be testing for less fickle T-cell responses as well.) People without clear-cut symptoms may not test at all, or may not test properly. And all on its own, the immune system can guard people against infection, especially in the period shortly after vaccination or illness. With HIV, a virus that causes chronic infections, lacks a vaccine, and spreads through clear-cut routes in concentrated social networks, it was easier to identify those individuals whom the virus had visited but not put down permanent roots within, says Ravindra Gupta, a virologist at the University of Cambridge. SARS-CoV-2 wont afford science the same ease of study.

Read: Is BA.5 the reinfection wave?

A full analogue to the HIV, malaria, and norovirus stories may not be possible. Genuine resistance can manifest in only so many ways, and tends to be born out of mutations that block a pathogens ability to force its way into a cell, or xerox itself once its inside. CCR5, Duffy, and the sugars dropped by FUT2, for instance, all act as microbial landing pads; mutations rob the bugs of those perches. If an equivalent mutation exists to counteract SARS-CoV-2, it might logically be found in, say, ACE2, the receptor that the coronavirus needs in order to break into cells, or TMPRSS2, a scissors-like protein that, for at least some variants, speeds the invasive process along. Already, researchers have found that certain genetic variations can dial down ACE2s presence on cells, or pump out junkier versions of TMPRSS2hints that there could be tweaks that further strip away the molecules. But ACE2 is very important to blood-pressure regulation and the maintenance of lung-tissue health, said Su, of NIAID, whos one of many scientists collaborating with Casanova to find SARS-CoV-2 resistance genes. A mutation that keeps the coronavirus out might very well muck around with other aspects of a persons physiology. That could make the genetic tweak vanishingly rare, debilitating, or even, as Gupta put it, not compatible with life. People with the CCR5-32 mutation, which halts HIV, are basically completely normal, Cannon told me, which means HIV kind of messed up in choosing CCR5. The coronavirus, by contrast, has figured out how to exploit something vital to its hostan ingenious invasive move.

The superpowers of genetic resistance can have other forms of kryptonite. A few strains of HIV have figured out a way to skirt around CCR5, and glom on to another molecule, called CXCR4; against this version of the virus, even people with the 32 mutation are not safe. A similar situation has arisen with Plasmodium vivax, which we do see in some Duffy-negative individuals, suggesting that the parasite has found a back door, says Dyann Wirth, a malaria researcher at Harvards School of Public Health. Evolution is a powerful strategyand with SARS-CoV-2 spewing out variants at such a blistering clip, I wouldnt necessarily expect resistance to be a checkmate move, Cannon told me. BA.1, for instance, conjured mutations that made it less dependent on TMPRSS2 than Delta was.

Read: The BA.5 wave is what COVID normal looks like

Still, protection doesnt have to be all or nothing to be a perk. Partial genetic resistance, too, can reshape someones course of disease. With HIV, researchers have pinpointed changes in groups of so-called HLA genes that, through their impact on assassin-like T cells, can ratchet down peoples risk of progressing to AIDS. And a whole menagerie of mutations that affect red-blood-cell function can mostly keep malaria-causing parasites at baythough many of these changes come with a huge human cost, Wirth told me, saddling people with serious clotting disorders that can sometimes turn lethal themselves.

With COVID-19, too, researchers have started to home in on some trends. Casanova, at Rockefeller, is one of several scientists who has led efforts unveiling the importance of an alarm-like immune molecule called interferon in early control of infection. People who rapidly pump out gobs of the protein in the hours after infection often fare just fine against the virus. But those whose interferon responses are weak or laggy are more prone to getting seriously sick; the same goes for people whose bodies manufacture maladaptive antibodies that attack interferon as it passes messages between cells. Other factors could toggle the risk of severe disease up or down as well: cells ability to sense the virus early on; the amount of coordination between different branches of defense; the brakes the immune system puts on itself, so it does not put the hosts own tissues at risk. Casanova and his colleagues are also on the hunt for mutations that might alter peoples risk of developing long COVID and other coronaviral consequences. None of these searches will be easy. But they should be at least simpler than the one for resistance to infection, Casanova told me, because the outcomes theyre measuringserious and chronic forms of diseaseare that much more straightforward to detect.

If resistance doesnt pan out, that doesnt have to be a letdown. People dont need total blockades to triumph over microbesjust a defense thats good enough. And the protection were born with isnt all the leverage weve got. Unlike genetics, immunity can be easily built, modified, and strengthened over time, particularly with the aid of vaccines. Those DIY defenses are probably what kept Carringtons case of COVID down to a mild course, she told me. Immune protection is also a far surer bet than putting a wager on what we may or may not inherit at birth. Better to count on the protections we know we can cook up ourselves, now that the coronavirus is clearly with us for good.

More here:
Could Genetics Be the Key to Never Getting the Coronavirus? - The Atlantic

James Noonan

James Noonan, who has made critical and novel contributions to the fields of human evolutionary genetics and neurodevelopment, was recently appointed the Albert E. Kent Professor of Genetics and Professor of Neuroscience, effective immediately.

Noonan received his B.S. in biology and English literature from the State University of New York at Binghamton in 1997, and his Ph.D. in genetics from Stanford University School of Medicine in 2004. He completed a postdoctoral fellowship in the Genomics Division at Lawrence Berkeley National Laboratory from 2004 to 2007. In 2007, he was recruited to Yale as assistant professor and was promoted to associate professor in 2013, and professor in 2021. He has a secondary appointment in Yales Department of Neuroscience.

Noonans research program is focused on deciphering the role of gene regulatory changes in the evolution of uniquely human traits. This work addresses a central hypothesis in human evolution, proposed more than 40 years ago: that changes in the level, timing, and location of gene expression account for biological differences between humans and other primates. Noonan has discovered thousands of human-specific genetic changes that alter gene expression and regulation, and by pioneering novel genetic models, his lab has begun to reveal how human-specific regulatory changes alter developmental traits. His work has provided key insights into the genetic origins of human biological uniqueness and has driven the rise of a new field: human evolutionary developmental biology.

Noonans seminal research discovered two classes of gene regulatory elements implicated in human evolution. The first are Human Accelerated Regions (HARs), which encode transcriptional enhances which are highly conserved across species and show many human-specific sequence changes (Science 2006, Science 2008). Using humanized mouse models, he has shown that HARs alter developmental gene expression and drive the evolution of novel phenotypes. As an example, he recently showed that one HAR altered expression of a transcription factor that has a role in limb development, possibly contributing to changes in skeletal patterning in human limb evolution (Nature Communications, 2022). These findings provide mechanistic insight into how HARs modified gene expression in human evolution. Using massively parallel assays, he has also comprehensively characterized the effect of thousands of human-specific sequence changes in HARs on their activity during neurodevelopment (Proceedings of the National Academy of Sciences, 2021)

He also identified thousands of human-specific changes in enhancer activity by direct analysis of developing human and nonhuman tissues. These loci, termed Human Gain Enhancers (HGEs), have gained activity in the developing human limb (Cell, 2013) and cerebral cortex (Science, 2015). These studies identified the biological pathways in limb and cortical development likely altered by human-specific regulatory changes, providing the basis for understanding their effects using genetic and experimental models.

Noonan has also contributed substantially to the educational programs of Yale School of Medicine, revolutionizing its graduate training landscape and empowering experimental genetics research across many labs at Yale. He designed the first course in genomics in the medical school more than 12 years ago, serving hundreds of students and faculty with the skills required to excel at the frontier of modern biomedical science. His training efforts have helped to set the standards of genomic research at Yale and ensured that the university remains a world leader in genomics.

See the original post here:
Noonan appointed Kent Professor of Genetics and Professor of Neuroscience - Yale News

July 20, 2022July 20, 2022

Today is Gregor Mendels 200th birthday andcelebrationsare being heldall across the globe.

Why the fuss over anAugustinian monkfrom the 1800s who grew peas in the garden of the abbey where he lived?

Because breeding and studying those pea plants led Mendel to discover the fundamental laws of inheritance, earning him wide recognition as the father of modern genetics. Today, researchers from Clemson University and those across the world are using genetics in ways Mendel would never have dreamed for personalized medicine that tailors disease prevention and treatment, to breed drought- and disease-resilient crops, and to improve the health of agricultural crops and animals.

It all goes back to Mendel paying attention to what was happening right there around him. Mendel was the first person to really understand that traits can be quantified and inherited in a predictable way. Thats the foundation of genetics, full stop. Thats where it starts, said David F. Clayton, chair of the Clemson UniversityDepartment of Genetics and Biochemstry. Of course, in the years since, such great progress has been made in how that actually happens.

Back when Mendel started growing his pea plants, it was thought that traits in offspring were a result of a blending of traits of each parent, kind of like mixing paint.

Mendel studied seven traits of pea plants: seed color, seed shape, flower position, flower color, pod shape, pod color and stem length. He noticed when he cross-pollinated a pea plant with yellow pods with one that had green pods, he didnt get plants with yellowish-green pods. Instead, all of them were yellow. However, when that crop self-pollinated, 75% of the second generation were yellow and 25% were green. Mendel concluded that each individual had two complete sets of inheritable factors, one from each parent. He attributed that generation-skipping to some characteristics being dominant and some being recessive.

Since then, our knowledge of genetics has grown by leaps and bounds. After all, Mendel didnt know about genes or DNA, and sequencing of the human genome wasnt completed until 2003.

Today, genetics is all around us, woven into our daily live in small and large ways.

The Clemson University Center for Human Genetics and the College of Science will celebrate Mendels birthday with a lecture by Daniel J. Fairbanks of Utah Valley University on Sept. 2 at 2:30 p.m. The lecture, Gregor Mendel at the Bicentennial of his Birth: The Life and Legacy of a Scientific Genius, will be held on Zoom. It is part of the College of Sciences Discover Science Lecture Series.

The College of Science pursues excellence in scientific discovery, learning, and engagement that is both locally relevant and globally impactful. The life, physical and mathematical sciences converge to tackle some of tomorrows scientific challenges, and our faculty are preparing the next generation of leading scientists. The College of Science offers high-impact transformational experiences such as research, internships and study abroad to help prepare our graduates for top industries, graduate programs and health professions. clemson.edu/science

Or email us at news@clemson.edu

Continued here:
Happy 200th birthday, Gregor Mendel: 5 ways the father of modern genetics impacted your life today - Clemson News

Johri, A. K. et al. Group B Streptococcus: global incidence and vaccine development. Nat. Rev. Microbiol. https://doi.org/10.1038/nrmicro1552 (2006).

Nizet, V. I., Ferrieri, P. A. & Rubens, C. E. Molecular pathogenesis of group B streptococcal disease in newborns. Streptococcal Infect. Clin. Asp. Microbiol. Mol. Pathog. 180221 (Oxford Univ. Press, New York, NY, 2000).

Davies, H. G., Carreras-Abad, C., Le Doare, K. & Heath, P. T. Group B Streptococcus: trials and tribulations. Pediatr. Infect. Dis. J. https://doi.org/10.1097/INF.0000000000002328 (2019).

Seale, A. C. et al. Estimates of the burden of Group B Streptococcal disease worldwide for pregnant women, stillbirths, and children. Clin. Infect. Dis. https://doi.org/10.1093/cid/cix664 (2017).

World Health Organisation. Group B Streptococcus Vaccine: Full Value of Vaccine Assessment. Financial Analysis. (World Health Organisation, 2021).

Schuchat, A. Epidemiology of group B streptococcal disease in the United States: Shifting paradigms. Clin. Microbiol. Rev. https://doi.org/10.1128/cmr.11.3.497 (1998).

Bekker, V., Bijlsma, M. W., van de Beek, D., Kuijpers, T. W. & Van der Ende, A. Incidence of invasive group B streptococcal disease and pathogen genotype distribution in newborn babies in the Netherlands over 25 years: a nationwide surveillance study. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(14)70919-3 (2014).

Bevan, D., White, A., Marshall, J. & Peckham, C. Modelling the effect of the introduction of antenatal screening for group B Streptococcus (GBS) carriage in the UK. BMJ Open https://doi.org/10.1136/bmjopen-2018-024324 (2019).

Ancona, R. J., Ferrieri, P. & Williams, P. P. Maternal factors that enhance the acquisition of group-B streptococci by newborn infants. J. Med. Microbiol. 13, 273280 (1980).

CAS PubMed Article Google Scholar

Tazi, A. et al. Risk factors for infant colonization by hypervirulent CC17 group B Streptococcus: toward the understanding of late-onset disease. Clin. Infect. Dis. 69, 17401748 (2019).

CAS PubMed Article Google Scholar

Gizachew, M. et al. Proportion of Streptococcus agalactiae vertical transmission and associated risk factors among Ethiopian mother-newborn dyads, Northwest Ethiopia. Sci. Rep. 10, 3477 (2020).

ADS CAS PubMed PubMed Central Article Google Scholar

Hung, L.-C. et al. Risk factors for neonatal early-onset group B streptococcus-related diseases after the implementation of a universal screening program in Taiwan. BMC Public Health 18, 438 (2018).

PubMed PubMed Central Article Google Scholar

Schrag, S. J. et al. A population-based comparison of strategies to prevent early-onset group B Streptococcal disease in neonates. N. Engl. J. Med. 347, 233239 (2002).

PubMed Article Google Scholar

Lawn, J. E. et al. Every country, every family: time to act for group B Streptococcal disease worldwide. Clin. Infect. Dis. ciab859, https://doi.org/10.1093/cid/ciab859 (2021).

Romain, A.-S. et al. Clinical and laboratory features of group B Streptococcus meningitis in infants and newborns: study of 848 cases in France, 20012014. Clin. Infect. Dis. 66, 857864 (2018).

PubMed Article Google Scholar

Alhhazmi, A., Hurteau, D. & Tyrrell, G. J. Epidemiology of invasive group B Streptococcal disease in Alberta, Canada, from 2003 to 2013. J. Clin. Microbiol. 54, 17741781 (2016).

CAS PubMed PubMed Central Article Google Scholar

Moore, M. R., Schrag, S. J. & Schuchat, A. Effects of intrapartum antimicrobial prophylaxis for prevention of group-B-streptococcal disease on the incidence and ecology of early-onset neonatal sepsis. Lancet Infect. Dis. 3, 201213 (2003).

PubMed Article Google Scholar

Ohlsson, A. & Shah, V. S. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD007467.pub4 (2014).

Nishihara, Y., Dangor, Z., French, N., Madhi, S. & Heyderman, R. Challenges in reducing group B Streptococcus disease in African settings. Arch. Dis. Child. 102, 72 LP72 77 (2017).

Article Google Scholar

Buurman, E. T. et al. A novel hexavalent capsular polysaccharide conjugate vaccine (GBS6) for the prevention of neonatal group b streptococcal infections by maternal immunization. J. Infect. Dis. https://doi.org/10.1093/infdis/jiz062 (2019).

Madhi, S. A. et al. Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in healthy women and their infants: a randomised phase 1b/2 trial. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(16)00152-3 (2016).

Heyderman, R. S. et al. Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(15)00484-3 (2016).

Nilo, A. et al. Anti-group B Streptococcus glycan-conjugate vaccines using pilus protein GBS80 as carrier and antigen: comparing lysine and tyrosine-directed conjugation. ACS Chem. Biol. https://doi.org/10.1021/acschembio.5b00247 (2015).

Absalon, J. et al. Safety and immunogenicity of a novel hexavalent group B streptococcus conjugate vaccine in healthy, non-pregnant adults: a phase 1/2, randomised, placebo-controlled, observer-blinded, dose-escalation trial. Lancet Infect. Dis. 21, 263274 (2021).

CAS PubMed Article Google Scholar

Martin, T. R., Ruzinski, J. T., Rubens, C. E., Chi, E. Y. & Wilson, C. B. The effect of type-specific polysaccharide capsule on the clearance of group B Streptococci from the lungs of infant and adult rats. J. Infect. Dis. 165, 306314 (1992).

CAS PubMed Article Google Scholar

Marques, M. B., Kasper, D. L., Pangburn, M. K. & Wessels, M. R. Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B streptococci. Infect. Immun. https://doi.org/10.1128/iai.60.10.3986-3993.1992 (1992).

Uchiyama, S. et al. Dual actions of group B Streptococcus capsular sialic acid provide resistance to platelet-mediated antimicrobial killing. Proc. Natl. Acad. Sci. USA. https://doi.org/10.1073/pnas.1815572116 (2019).

Herbert, M. A., Beveridge, C. J. E. & Saunders, N. J. Bacterial virulence factors in neonatal sepsis: group B streptococous. Curr. Opin. Infect. Dis. https://doi.org/10.1097/00001432-200406000-00009 (2004).

Lynskey, N. N. et al. Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase. PLOS Pathog. 13, e1006493 (2017).

PubMed PubMed Central Article CAS Google Scholar

Bryan, J. D. & Shelver, D. W. Streptococcus agalactiae CspA is a serine protease that inactivates chemokines. J. Bacteriol. 191, 18471854 (2009).

CAS PubMed Article Google Scholar

Poyart, C. et al. Contribution of Mn-cofactored superoxide dismutase (SodA) to the virulence of Streptococcus agalactiae. Infect. Immun. 69, 50985106 (2001).

CAS PubMed PubMed Central Article Google Scholar

Gibson, R. L., Nizet, V. & Rubens, C. E. Group B Streptococcal -hemolysin promotes injury of lung microvascular endothelial cells. Pediatr. Res. 45, 626634 (1999).

CAS PubMed Article Google Scholar

Zhu, L. et al. Genetic basis underlying the hyperhemolytic phenotype of Streptococcus agalactiae strain CNCTC10/84. J. Bacteriol. 202, e00504e00520 (2020).

CAS PubMed PubMed Central Google Scholar

Deng, L. et al. Characterization of a two-component system transcriptional regulator, LtdR, that impacts group B Streptococcal colonization and disease. Infect. Immun. 86, e0082217 (2018).

CAS PubMed PubMed Central Article Google Scholar

Wang, N.-Y. et al. Group B streptococcal serine-rich repeat proteins promote interaction with fibrinogen and vaginal colonization. J. Infect. Dis. 210, 982991 (2014).

CAS PubMed PubMed Central Article Google Scholar

Buscetta, M. et al. FbsC, a novel fibrinogen-binding protein, promotes Streptococcus agalactiae-host cell interactions. J. Biol. Chem. 289, 2100321015 (2014).

CAS PubMed PubMed Central Article Google Scholar

Doran, K. S. et al. Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid. J. Clin. Invest. 115, 24992507 (2005).

CAS PubMed PubMed Central Article Google Scholar

Almeida, A. et al. Whole-genome comparison uncovers genomic mutations between group B Streptococci sampled from infected newborns and their mothers. J. Bacteriol. 197, 33543366 (2015).

CAS PubMed PubMed Central Article Google Scholar

Andrea, G. et al. Pan-GWAS of Streptococcus agalactiae highlights lineage-specific genes associated with virulence and niche adaptation. MBio 11, e0072820 (2021).

Google Scholar

Read, T. D. & Massey, R. C. Characterizing the genetic basis of bacterial phenotypes using genome-wide association studies: a new direction for bacteriology. Genome Med. 6, 109 (2014).

PubMed PubMed Central Article CAS Google Scholar

Power, R. A., Parkhill, J. & De Oliveira, T. Microbial genome-wide association studies: lessons from human GWAS. Nat. Rev. Genet. https://doi.org/10.1038/nrg.2016.132 (2016).

Lees, J. A. et al. Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis. Microb. Genomics 3, e000103e000103 (2017).

Google Scholar

Lilje, B. et al. Whole-genome sequencing of bloodstream Staphylococcus aureus isolates does not distinguish bacteraemia from endocarditis. Microb. Genomics 3, e000138 (2017).

Google Scholar

Lees, J. A. et al. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis. Nat. Commun. https://doi.org/10.1038/s41467-019-09976-3 (2019).

Li, Y. et al. Genome-wide association analyses of invasive pneumococcal isolates identify a missense bacterial mutation associated with meningitis. Nat. Commun. 10, 178 (2019).

ADS PubMed PubMed Central Article CAS Google Scholar

Young, B. C. et al. Panton-valentine leucocidin is the key determinant of staphylococcus aureus pyomyositis in a bacterial GWAS. Elife https://doi.org/10.7554/eLife.42486 (2019).

Kulohoma, B. W. et al. Comparative genomic analysis of meningitis- and bacteremia-causing pneumococci identifies a common core genome. Infect. Immun. 83, 41654173 (2015).

Davies, M. R. et al. Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics. Nat. Genet. 51, 10351043 (2019).

CAS PubMed PubMed Central Article Google Scholar

Chaguza, C. et al. Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism. Commun. Biol. 3, 559 (2020).

CAS PubMed PubMed Central Article Google Scholar

Laabei, M. et al. Predicting the virulence of MRSA from its genome sequence. Genome Res. https://doi.org/10.1101/gr.165415.113 (2014).

Coll, F. et al. Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis. Nat. Genet. https://doi.org/10.1038/s41588-017-0029-0 (2018).

Chewapreecha, C. et al. Comprehensive identification of single nucleotide polymorphisms associated with beta-lactam resistance within pneumococcal mosaic genes. PLoS Genet. 10, e1004547e1004547 (2014).

PubMed PubMed Central Article CAS Google Scholar

Farhat, M. R. et al. Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis. Nat. Genet. 45, 11831189 (2013).

CAS PubMed PubMed Central Article Google Scholar

Suzuki, M., Shibayama, K. & Yahara, K. A genome-wide association study identifies a horizontally transferred bacterial surface adhesin gene associated with antimicrobial resistant strains. Sci. Rep. 6, 37811 (2016).

ADS CAS PubMed PubMed Central Article Google Scholar

Hicks, N. D., Carey, A. F., Yang, J., Zhao, Y. & Fortune, S. M. Bacterial genome-wide association identifies novel factors that contribute to ethionamide and prothionamide susceptibility in Mycobacterium tuberculosis. MBio 10, e00616e00619 (2019).

CAS PubMed PubMed Central Article Google Scholar

Sieber, R. N. et al. Genome investigations show host adaptation and transmission of LA-MRSA CC398 from pigs into Danish healthcare institutions. Sci. Rep. 9, 18655 (2019).

ADS CAS PubMed PubMed Central Article Google Scholar

Ma, K. C. et al. Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae. Nat. Commun. 11, 4126 (2020).

ADS CAS PubMed PubMed Central Article Google Scholar

Chewapreecha, C. et al. Genetic variation associated with infection and the environment in the accidental pathogen Burkholderia pseudomallei. Commun. Biol. 2, 428 (2019).

CAS PubMed PubMed Central Article Google Scholar

Jamrozy, D. et al. Increasing incidence of group B streptococcus neonatal infections in the Netherlands is associated with clonal expansion of CC17 and CC23. Sci. Rep. 10, 9539 (2020).

ADS PubMed PubMed Central Article CAS Google Scholar

Bianchi-Jassir, F. et al. Systematic review of Group B Streptococcal capsular types, sequence types and surface proteins as potential vaccine candidates. Vaccine https://doi.org/10.1016/j.vaccine.2020.08.052 (2020).

Nicola, J. et al. Multilocus sequence typing system for group B Streptococcus. J. Clin. Microbiol. 41, 25302536 (2003).

Article CAS Google Scholar

Cheng, L., Connor, T. R., Sirn, J., Aanensen, D. M. & Corander, J. Hierarchical and spatially explicit clustering of DNA sequences with BAPS software. Mol. Biol. Evol. 30, 12241228 (2013).

CAS PubMed PubMed Central Article Google Scholar

View post:
Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion - Nature.com

A majority of people in the U.S have had Covid-19 at least once likely more than 70% of the country, White House Covid-19 Response Coordinator Ashish Jha said on Thursday, citing data from the Centers for Disease Control and Prevention.

Many have been infected multiple times. In a study that has not been peer viewed that looked at 257,000 U.S. veterans who'd contracted Covid at least once, 12% had a reinfection by April and about 1% had been infected three times or more.

This raises an obvious question: What is keeping that shrinking minority of people from getting sick?

Disease experts are homing in on a few predictive factors beyond individual behavior, including genetics, T cell immunity and the effects of inflammatory conditions like allergies and asthma.

But even as experts learn more about the reasons people may be better equipped to avoid Covid, they caution that some of these defenses may not hold up against the latest version of omicron, BA.5, which is remarkably good at spreading and evading vaccine protection.

"It really takes two to tango," said Neville Sanjana, a bioengineer at the New York Genome Center. "If you think about having an infection and any of the bad stuff that happens after that, it really is a product of two different organisms: the virus and the human."

In 2020, New York University researchers identified a multitude of genes that could affect a person's susceptibility to the coronavirus. In particular, they found that inhibiting certain genes that code for a receptor known as ACE2, which allows the virus to enter cells, could reduce a person's likelihood of infection.

Sanjana, who conducted that research, estimated that about 100 to 500 genes could influence Covid-19 susceptibility in sites like the lungs or nasal cavity.

Genetics is "likely to be a large contributor" to protection from Covid-19, he said. "I would never say its the only contributor."

In July, researchers identified a common genetic factor that could influence the severity of a coronavirus infection. In a study of more than 3,000 people, two genetic variations decreased the expression of a gene called OAS1, which is part of the innate immune response to viral infections. That was associated with an increased risk of Covid-19 hospitalization.

Increasing the gene's expression, then, should have the opposite effect reducing the risk of severe disease though it wouldn't necessarily prevent infection altogether.

"Its very natural to get infected once you are exposed. Theres no magic bullet for that. But after you get infected, how youre going to respond to this infection, thats what is going to be affected by your genetic variants," said Ludmila Prokunina-Olsson, the study's lead researcher and chief of the Laboratory of Translational Genomics at the National Cancer Institute.

Still, Benjamin tenOever, a microbiology professor at the NYU Grossman School of Medicine who helped conduct the 2020 research, said it would be difficult for scientists to pinpoint a particular gene responsible for preventing a Covid infection.

"While there might still be certainly some genetics out there that do render people completely resistant, theyre going to be incredibly hard to find," tenOever said. "People have already been looking intensely for two years with no actual results."

Aside from this new coronavirus, SARS-CoV-2, four other coronaviruses commonly infect people, typically causing mild to moderate upper respiratory illnesses like the common cold.

A recent study suggested that repeated exposure to or occasional infections from these common cold coronaviruses may confer some protection from SARS-CoV-2.

The researchers found that T cells, a type of white blood cell that recognizes and fights invaders, seem to recognize SARS-CoV-2 based on past exposure to other coronaviruses. So when a person who has been infected with a common cold coronavirus is later exposed to SARS-CoV-2, they might not get as sick.

But that T cell memory probably can't prevent Covid entirely.

"While neutralizing antibodies are key to prevent an infection, T cells are key to terminate an infection and to modulate the severity of infection," said Alessandro Sette, the studys author and a professor at the La Jolla Institute for Immunology.

Sette said it's possible that some people's T cells clear the virus so quickly that the person never tests positive for Covid. But researchers aren't yet sure if that's what's happening.

"Its possible that, despite being negative on the test, it was a very abortive, transient infection that was not detected," Sette said.

At the very least, he said, T cells from past Covid infections or vaccines should continue to offer some protection against coronavirus variants, including BA.5.

Although asthma was considered a potential risk factor for severe Covid earlier in the pandemic, more recent research suggests that low-grade inflammation from conditions like allergies or asthma may have a protective benefit.

"Youll hear these stories about some individuals getting sick and having full-blown symptoms of Covid, and having slept beside their partner for an entire week during that period without having given it to them. People think that they must have some genetic resistance to it, [but] a big part of that could be if the partner beside them in any way has a higher than normal inflammatory response going on in their lungs," tenOever said.

A May study found that having a food allergy halved the risk of a coronavirus infection among nearly 1,400 U.S. households. Asthma didn't lower people's risk of infection in the study, but it didn't raise it, either.

One theory, according to the researchers, is that people with food allergies express fewer ACE2 receptors on the surface of their airway cells, making it harder for the virus to enter.

"Because there are fewer receptors, you will have either a much lower grade infection or just be less likely to even become infected," said Tina Hartert, a professor of medicine and pediatrics at the Vanderbilt University School of Medicine, who co-led that research.

The study took place from May 2020 to February 2021, before the omicron variant emerged. But Hartert said BA.5 likely wouldn't eliminate cross-protection from allergies.

"If something like allergic inflammation is protective, I think it would be true for all variants," Hartert said. "The degree to which it could be protective could certainly differ."

For many, the first explanation that springs to mind when thinking about Covid avoidance is one's personal level of caution. NYU's TenOever believes that individual behavior, more than genetics or T cells, is the key factor. He and his family in New York City are among those who've never had Covid, which he attributes to precautions like staying home and wearing masks.

"I dont think for a second that we have anything special in our genetics that makes us resistant," he said.

It's now common knowledge that Covid was easier to avoid before omicron, back when a small percentage of infected people were responsible for the majority of the virus's spread. A 2020 study, for example, found that 10% to 20% of infected people accounted for 80% of transmissions.

But omicron and its subvariants have made any social interaction riskier for everyone involved.

"It's probably far more of an equal playing field with the omicron variants than it ever was for the earlier variants," tenOever said.

BA.5, in particular, has increased the odds that people who've avoided Covid thus far will get sick. President Joe Biden is a prime example: He tested positive for the first time this week.

But even so, Jha said on Thursday in a news briefing, "I dont believe that every American will be infected."

Follow this link:
Scientists are narrowing in on why some people keep avoiding Covid. BA.5 could end that luck. - NBC News