Daily Archives: April 27, 2024

By Lauren Sausser April 25, 2024

CHARLESTON, S.C. When he recently walked into the dental clinic at the Medical University of South Carolina donning a bright-blue pullover with In Our DNA SC embroidered prominently on the front, Lee Moultrie said, two Black women stopped him to ask questions.

Its a walking billboard, said Moultrie, a health care advocate who serves on the community advisory board for In Our DNA SC, a study underway at the university that aims to enroll 100,000 South Carolinians including a representative percentage of Black people in genetics research. The goal is to better understand how genes affect health risks such as cancer and heart disease.

Moultrie, who is Black and has participated in the research project himself, used the opportunity at the dental clinic to encourage the women to sign up and contribute their DNA. He keeps brochures about the study in his car and at the barbershop he visits weekly for this reason. Its one way he wants to help solve a problem that has plagued the field of genetics research for decades: The data is based mostly on DNA from white people.

Project leaders in Charleston told KFF Health News in 2022 that they hoped to enroll participants who reflect the demographic diversity of South Carolina, where just under 27% of residents identify as Black or African American. To date, though, theyve failed to hit that mark. Only about 12% of the projects participants who provided sociodemographic data identify as Black, while an additional 5% have identified as belonging to another racial minority group.

Wed like to be a lot more diverse, acknowledged Daniel Judge, principal investigator for the study and a cardiovascular genetics specialist at the Medical University of South Carolina.

Lack of diversity in genetics research has real health care implications. Since the completion more than 20 years ago of the Human Genome Project, which mapped most human genes for the first time, close to 90% of genomics studies have been conducted using DNA from participants of European descent, research shows. And while human beings of all races and ancestries are more than 99% genetically identical, even small differences in genes can spell big differences in health outcomes.

Precision medicine is a term used to describe how genetics can improve the way diseases are diagnosed and treated by considering a persons DNA, environment, and lifestyle. But if this emerging field of health care is based on research involving mostly white people, it could lead to mistakes, unknowingly, said Misa Graff, an associate professor in epidemiology at the University of North Carolina and a genetics researcher.

In fact, thats already happening. In 2016, for example, research found that some Black patients had been misdiagnosed with a potentially fatal heart condition because theyd tested positive for a genetic variant thought to be harmful. That variant is much more common among Black Americans than white Americans, the research found, and is considered likely harmless among Black people. Misclassifications can be avoided if even modest numbers of people from diverse populations are included in sequence databases, the authors wrote.

The genetics research project in Charleston requires participants to complete an online consent form and submit a saliva sample, either in person at a designated lab or collection event or by mail. They are not paid to participate, but they do receive a report outlining their DNA results. Those who test positive for a genetic marker linked to cancer or high cholesterol are offered a virtual appointment with a genetics counselor free of charge.

Some research projects require more time from their volunteers, which can skew the pool of participants, Graff said, because not everyone has the luxury of free time. We need to be even more creative in how we obtain people to help contribute to studies, she said.

Moultrie said he recently asked project leaders to reach out to African American media outlets throughout the Palmetto State to explain how the genetics research project works and to encourage Black people to participate. He also suggested that when researchers talk to Black community leaders, such as church pastors, they ought to persuade those leaders to enroll in the study instead of simply passing the message along to their congregations.

We have new ideas. We have ways we can do this, Moultrie said. Well get there.

Other ongoing efforts are already improving diversity in genetics research. At the National Institutes of Health, a program called All of Us aims to analyze the DNA of more than 1 million people across the country to build a diverse health database. So far, that program has enrolled more than 790,000 participants. Of these, more than 560,000 have provided DNA samples and about 45% identify as being part of a racial or ethnic minority group.

Diversity is so important, said Karriem Watson, chief engagement officer for the All of Us research program. When you think about groups that carry the greatest burden of disease, we know that those groups are often from minoritized populations.

Diverse participation in All of Us hasnt come about by accident. NIH researchers strategically partnered with community health centers, faith-based groups, and Black fraternities and sororities to recruit people who have been historically underrepresented in biomedical research.

In South Carolina, for example, the NIH works with Cooperative Health, a network of federally qualified health centers near the state capital that serve many patients who are uninsured and Black, to recruit patients for All of Us. Eric Schlueter, chief medical officer of Cooperative Health, said the partnership works because their patients trust them.

We have a strong history of being integrated into the community. Many of our employees grew up and still live in the same communities that we serve, Schlueter said. That is what is part of our secret sauce.

So far, Cooperative Health has enrolled almost 3,000 people in the research program, about 70% of whom are Black.

Our patients are just like other patients, Schlueter said. They want to be able to provide an opportunity for their children and their childrens children to have better health, and they realize this is an opportunity to do that.

Theoretically, researchers at the NIH and the Medical University of South Carolina may be trying to recruit some of the same people for their separate genetics studies, although nothing would prevent a patient from participating in both efforts.

The researchers in Charleston acknowledge they still have work to do. To date, In Our DNA SC has recruited about half of the 100,000 people it hopes for, and of those, about three-quarters have submitted DNA samples.

Caitlin Allen, a program investigator and a public health researcher at the medical university, acknowledged that some of the programs tactics havent succeeded in recruiting many Black participants.

For example, some patients scheduled to see providers at the Medical University of South Carolina receive an electronic message through their patient portal before an appointment, which includes information about participating in the research project. But studies show that racial and ethnic minorities are less likely to engage with their electronic health records than white patients, Allen said.

We see low uptake with that strategy, she said, because many of the people researchers are trying to engage likely arent receiving the message.

The study involves four research coordinators trained to take DNA samples, but theres a limit to how many people they can talk to face-to-face. Were not necessarily able to go into every single room, Allen said.

That said, in-person community events seem to work well for enrolling diverse participants. In March, In Our DNA SC research coordinators collected more than 30 DNA samples at a bicentennial event in Orangeburg, South Carolina, where more than 60% of residents identify as Black. Between the first and second year of the research project, Allen said, In Our DNA SC doubled the number of these community events that research coordinators attended.

I would love to see it ramp up even more, she said.

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Genetics Studies Have a Diversity Problem That Researchers Struggle To Fix - Kaiser Health News

Ward Raymond Thomas went missing from the Chillicothe VA Medical Center in 1972. Decades later, his family has closure with the help of genetic genealogy testing.

CHILLICOTHE, Ohio Ohio World War II veteran, Ward Raymond Thomas, was laid to rest in April in a traditional military service in Chillicothe.

The path to get to that moment was anything but traditional.

Thomas had been missing for more than 50 years.

In 1942, when Thomas was 24 years old, he joined the U.S. Army at Fort Hayes in Columbus and went to serve overseas in World War II.

He returned home three years later with a long list of accolades, including the Purple Heart, and was honorably discharged from service.

Years later in 1972, Thomas was being treated at the Chillicothe VA Medical Center when he disappeared.

His family searched for him, but for decades, what happened to Thomas would be a mystery, until his niece Carolyn Grandstaff got a phone call last year from investigators at the Ross County Coroners Office.

He asked me if Ward Thomas was my uncle, she said.

The investigator told her about a skull that had been discovered in the Scioto River near the Chillicothe Correctional Institute in 1996.

For years, the identity of the skull was a mystery, labeled John Doe, waiting at the coroners office for technology to catch up.

In our minds, we had done everything we could, until there was technology that came along. It was a cold case, said former Ross County Coroner Dr. John Gabis.

Decades later, Dr. Gabiss successor, Dr. Ben Trotter sent the skull to the state BCI lab for testing.

Technology finally caught up in a way that we could extract DNA from the bone, Dr. Trotter said.

There, scientists extracted enough DNA from a tooth on the skull to look further into its identity.

It was the non-profit, DNA Doe Project, that used genetic genealogy to come up with the name Ward Thomas.

They tracked down his living relatives and Grandstaffs DNA was a perfect match.

Shock, pure shock. I wish my mom was alive and my sisters too to be a part of this because they missed their brother, they loved their brother a lot, she said.

Grandstaff said Ward Thomas was one of 12 siblings. His siblings, wife and stepson have passed away.

For 52 years, the family held on to Thomas military medals, finally reuniting them with the soldier at a funeral organized by the Ross County Veterans Service Office.

Just thankful that he could get this honor. It is wonderful, someone who went to war and fought for our freedoms, it is very important, said Thomas niece, Debbie Riffle.

Lt. Col. Robert Leach organized the service and decided he was going to send off the American hero in the most honorable way possible.

He invited Thomas family, members of the coroner's office, the DNA Doe Project, local law enforcement and anyone who had a part in solving the more than 50-year mystery, even recruiting a local high school student to wear a replica of Thomas military uniform, complete with all of his awards, honors and medals.

What I feel we did today was give a name and a face and a family to Ward Thomas, so now it is more than just an interesting story about science and identification of remains. Now we have laid a World War II decorated combat veteran to rest with his comrades, Lt. Col. Leach said.

Thomas was laid to rest with fellow veterans at Greenlawn Cemetery in Chillicothe. The Ross County Veterans Service Office will place a flag at the site every Memorial Day.

The completed mission to identify a veteran offers hope for the more than 100 John and Jane Does in Ohio. Thomas case is one of the oldest to be solved through DNA at the BCI lab.

When it was sent out it was a smaller amount of DNA than theyre used to for genealogy, and it was successful so just the technology over the last few years in the genealogy world has advanced and its going to keep advancing, said BCI Criminal Intelligence Analyst Jennifer Lester.

Family members of missing persons are encouraged to submit their DNA for free throughProject LINK.

To learn more about the project, and how it could help solve your familys case, contact BCI at 855-BCI-OHIO or email LINK@OhioAttorneyGeneral.gov.

Read more:
WWII veteran Ward Thomas identified through genealogy testing - 10TV

A day in the life of DNA can be rough. It gets yanked across a dividing cell, zapped by radiation, and assaulted by chemicals. Luckily, cells have developed a complex set of repair mechanisms to protect vulnerable DNA and fix damage so that the cells genomic instruction manual remains intact. Cells use homologous recombination to stitch double-stranded breaks (DSB) back together and the enzyme telomerase to cap exposed ends of a DNA strand with a repetitive DNA sequence called a telomere.

However, if cells use the wrong repair mechanism for a given situation, it can be disastrous. For example, if telomerase tries to seal up a DSB, it can sever the chromosome, causing the cell to lose key genes. The whole system falls apart, said Titia de Lange, a cell biologist at Rockefeller University.

Scientists have observed that this can happen in yeast and corn, but whether it occurred in humans remained a mystery until now.1,2 de Langes team has finally figured out just how rare this catastrophic event is in humans and how cells keep it in check. In a study published in Science, they revealed that while telomerase occasionally acts at DSB, the ataxia telangiectasia and Rad3-related (ATR) protein typically runs interference to give the cell a chance to repair these breaks.3 The findings shed light on how this type of genomic instability could play a role in diseases such as cancer.

Continue reading below...

If telomeres formed at DSB, de Lange suspected that it would be infrequent, given how few telomerases there are in any cell and how much damage it would cause. We expected that this would be instantly repressed, de Lange said. Cells would not tolerate this.

Starting with immortalized HeLa cells with artificially high levels of telomerase, the researchers cut the cells DNA with Cas9 enzyme to create DSB. They carefully designed the system to target positions in the DNA that telomerase gravitates towards but that are not fatal to the cell when broken. As de Lange expected, telomerase added telomeres at the DSB, but this was very rare; telomerase only created approximately four new telomeres per 1,000 genomes.

I don't know if it's surprising that it occurs, or if it's surprising that it doesn't occur more often, said Nausica Arnoult, a cell biologist at the University of Colorado Boulder who was not involved in this study. It's really well controlled.

To figure out how the cells blocked telomerase from acting at DSB, de Langes team genetically inactivated many different enzymes and repair pathways to see if any of them repressed telomere formation. Eventually, they discovered the genomic guardian: ATR, a protein that senses DNA damage and triggers homologous recombination. When they inhibited ATR, the number of new telomeres nearly tripled.

In the process of pinpointing ATRs role, the researchers stumbled upon other cellular surprises. For example, they knew that certain proteins were required for telomerase to interact with DNA, but reducing those proteins levels didnt seem to block telomere formation at Cas9-induced DSB. They quickly realized that telomerase could act directly on the type of DNA cuts that Cas9 makes, which creates a little wrinkle in the use of CRISPR, de Lange said.

Arnoult agreed. Especially if you consider the therapeutic use of CRISPR-Cas9, we really need to understand if there are some contexts where that misguided action of telomerase is going to be more frequent, she said.

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Much remains for de Lange and her team to reveal about ATR. Although they found that ATR represses telomerase, they dont know how this happens. Arnoult said that she wonders whether there are other redundant pathways that can also influence telomere formation at DSB in other contexts. She pointed to other species where telomeres that form at DSB are a normal part of development.4,5 Studying those species may give us clues of how they can do that very efficiently and why it's prevented in humans, Arnoult said.

de Lange is also thinking about how this process could be involved in cancer. Cancer cells genomes are plagued by DNA breaks, but their survival and proliferation depends on them finding a way to stabilize that damaged DNA; inappropriate telomerase activity may be one tool at their disposal. de Langes team is creating cells with abnormal chromosomes similar to those in cancer to see if telomerase helps these cells survive.

1. Kramer KM, Haber JE. New telomeres in yeast are initiated with a highly selected subset of TG1-3 repeats.Genes Dev. 1993;7(12A):2345-56. 2. McClintock B. The stability of broken ends of chromosomes in Zea Mays.Genetics. 1941;26(2):234-82. 3. Kinzig CG, et al. ATR blocks telomerase from converting DNA breaks into telomeres.Science. 2024;383(6684):763-770. 4. Yu G, Blackburn EH. Developmentally programmed healing of chromosomes by telomerase in tetrahymena.Cell. 1991;67(4):823-32. 5. Mller F, et al. New telomere formation after developmentally regulated chromosomal breakage during the process of chromatin diminution in ascaris lumbricoides. Cell. 1991;67(4):815-22.

Originally posted here:
Keeping Telomeres in Their Places - The Scientist

RICHMOND, Va. Dayan Frias was immersed in the world of baseball from a young age. His dads heavy involvement within the sport gave Frias a front row seat of what a career in baseball would look like. Wherever his dad, David, was playing, training players, or managing a team throughout Colombia, Frias was right there watching.

It started with my family, watching them play and listening to them a lot I think thats what made my path toward baseball, he said in Spanish. I told [my dad] that I wanted to be like [the players] some day.

Naturally, the 21-year-old decided to embark on the journey of becoming a professional baseball player. The Cartagena, Colombia native trained with his dad and two-time Gold Glover Orlando Cabrera, played in different academies and attended tryouts and showcases. He didnt stop until he reached the goal of many aspiring ball players: to sign with a team.

The Guardians saw the potential in Frias and signed him as an international free agent in 2018 for $80,000. Having accomplished the goal of signing, the real work of honing his skills and developing his talents to fit the Guardians needs began.

Frias, the Guardians No. 29 prospect per MLB Pipeline, made notable improvements in his first two seasons as a rookie. He slashed .216/.383/.291 in 2019, then in 2021 he slashed .322/.420/.520. The 2020 season was canceled due to COVID.

While he had a good start, Frias struggled in his introduction to full-season ball in 2022, batting .239/.344/.330 and totaling 21 errors. Soon after the season was over, Frias was invited to play for Colombia in the 2023 World Baseball Classic in which he competed with and learned from veterans in the league.

It helped me a lot, getting to play and share moments with veterans in the Major Leagues, the infielder said. I got a lot of advice and I also picked up stuff from them, routines, small things that have helped me in this sport.

He took the advice and good habits with him to the regular season at High-A Lake County and found success in 2023. The switch hitter slashed .260/.356/.426 and recorded 88 hits, 43 runs, and 11 home runs. Defensively at third base, Frias dropped to 13 errors for Lake County. He received Midwest League Player of the Week honors in late July and was named a Caribbean Series All-Star in February.

Frias brought his routines and small things from last season and implemented them into the new season. The advice he received that has been the most impactful, Frias shares with everyone: See it and hit it.

If you dont see anything then you cant hit and nothing happens, he said. I try to find a pitch that I know Im going to hit well and execute it Trying to miss less is what Im looking for at home plate.

He saw results early, collecting two hits and an RBI in five at-bats during his third season in the Cactus League with the Guardians in 2024. His improvements helped the plus defender break into the Guardians Top 30 prospect rankings this season.

As his growth continues, Frias wants to be remembered for his own style of play radiating excitement and passion on and off the field. After all, he has a passion for baseball that has been growing ever since he was introduced to the sport by his dad. He hopes his energy spreads not only within the clubhouse, but to fans as well.

I like to enjoy the game because its what I love, to be here in front of these fans, he said. I play for my team as much as for the fans as well. I love to play with enthusiasm all the time. Youre always going to see me smiling and messing around with the guys, making jokes all the time. I like to be a happy guy and infect my teammates with happiness.

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This Guardians prospect has baseball in his DNA - 1330 WFIN