Ricki Lewis

The Roma people have long held a special fascination for population geneticists who study the frequencies of genetic diseases. The largest minority in Europe, the Roma number 10 to 12 million and live in scattered groups, mostly in central and southeastern Europe. A recent Comment in Nature, from a team at the University of Freiburg, explores how "Europe's Roma people are vulnerable to poor practice in genetics."

 

A Tragic History

 

The Roma, once called gypsies, likely originated in the Punjab region of northwest India about 1,500 years ago. They traveled to Persia (Iran), then through Armenia to the Balkan peninsula, and reached the Iberian peninsula by the 15th century. Their genomes diversified as people joined along the way. After their arrival in Portugal and Spain, persecution began. It was the beginning of extreme discrimination and isolation that would unfold over the years.

 

The Roma and the Jews became the targets of the Nazi goal of "racial hygiene." In 1936, investigators at The Race Hygiene and Population Biology Research Centre drew pedigrees of these groups to form the rationale of a "scientific basis" for the "final solution." German geneticists studied the Roma. Ferdinand Sauerbruch, nominated for a Nobel, submitted a grant proposal to conduct "genetic and medical research" in Auschwitz, which the Deutsche Forschungsgemeinschaft funded. Hundreds of thousands of Roma died in experiments.

To continue reading, go to DNA Science, where this post was first published.

I often marvel at the disconnect between media coverage of "breakthrough" treatments and the decades of research that lie behind them. A new drug is the culmination of basic research, preclinical experiments on animals and cells, three phases of clinical trials, and post-marketing surveillance. It takes decades.

 

A small, phase 1 study – safety in healthy people – caught my attention this week. The work was presented at the American College of Cardiology's annual meeting and published online in the Journal of the American Medical Association.

 

The healthy participants had elevated levels of apolipoprotein(a), which is made in the liver and goes to the blood, where it carries cholesterol. High levels raise risk of heart attack, stroke, and narrowing of the aorta. Could silencing the gene that encodes the protein portion of apolipoprotein(a) lower the level, perhaps even preventing the heart disease?

 

One way to silence a gene uses a natural process, RNA interference (RNAi), which blocks translation of a gene's information into construction of a specific protein. The first drug using RNAi was Onpattro, approved in 2018 to treat a rare form of amyloidosis. The disease causes tingling, tickling, and burning sensations and affects about 3,000 people in the US.

 

In the new study, the researchers injected tiny pieces of short interfering RNAs (siRNAs), which glommed onto the messenger RNAs for the protein part of apolipoprotein(a). The 32 healthy volunteers received placebo or ascending doses. Levels of apolipoprotein(a) fell in a dose-dependent manner, by about 98 percent for the highest-dose group. All doses were well tolerated and the lowering largely persisted when checked at five months.

 

To continue reading, go to my blog, DNA Science, at Public Library of Science.

I pity the 15 percent of the human population that cannot live with a cat, due to allergy. I've seen it happen, a guest's face blowing up. My best friend Wendy can visit here, where cats outnumber people two-to-one, only by megadosing on antihistamines and heading to the porch to breathe periodically. Even with that she's good for only a day or two.

 

But CRISPR gene editing may come to the rescue, someday.

 

Snip out the gene that encodes a protein called Fel d 1, and the kitty can no longer make a hapless human's eyes and nose run and bronchioles constrict in an asthma attack. That's what Nicole F. Brackett and a team from InBio have done in cat cells. Their work was just published in The CRISPR Journal. (If googling makes this news seems recycled, it's because an abstract appeared just before the world shut down in early 2020.)

 

CRISPR is a tool that can remove, replace, or add a selected bit of DNA to a chromosome. To counter cat allergy, CRISPR would delete the genes that encode the offending allergen.

 

To continue reading, go to my blog DNA Science, where this post first appeared.

As if the waves of novel variants of "interest" and "concern" sweeping the planet haven't been enough, and we find versions of SARS-CoV-2 dodging in and out of species in a complex pattern of spillovers and spillbacks, we discover that it's even sneakier. Two new papers in Nature Communications, from a group at the Max Planck Bristol Centre of Minimal Biology, describe how the virus can differ genetically in different parts of the same host.

 

That may mean that if vaccines and treatments vanquish the virus in the respiratory tract, the pathogen might persist elsewhere. And the viruses in new places replicate and infect more vigorously, better able to elude our immune response. That's not good news as protection from vaccinations or having had COVID-19 wanes.

 

To continue reading, go to DNA Science, where this post first appeared. 

In honor of Rare Disease Day 2022, February 28th, I'm reposting a DNA Science story from nine years ago. February 16th was 12 years since Jane Mervar lost her young daughter to Huntington's disease (HD). Thank you

Jane for always sharing your story! (Updates are in parentheses.)

 

Looking back, signs that Jane Mervar's husband, Karl, had HD started when their youngest daughter, Karli, began to have trouble paying attention in school. Karl had become abusive, paranoid, and unemployable due to his drunken appearance. Karli, born in September 1996, was hyperactive and had difficulty following directions.

 

When by age 5 Karli's left side occasionally stiffened and her movements slowed, Jane began the diagnostic journey that would end with Karli's diagnosis of HD, which had affected her paternal grandmother.

 

Soon Karli could no longer skip, hop, or jump. New troubles emerged. "She had cold sweats, tachycardia, and chronic itching. She fell and suffered chronic pain. By age 6 she was losing her speech and became withdrawn," Jane recalls. Karli drooled and her speech became unintelligible. By age 7 her weight had plunged, and by age 8 she had developed pneumonia three times, due to difficulty swallowing. By age 9 she required a feeding tube, suffered seizures, and would go long periods without sleep.

 

An Adult's Disease in a Child

 

This isn't the way that a disease is supposed to run in families, striking child before parent. HD is regarded as a disease of adulthood, but in fact about 10 percent of people with the condition are under age 20 – they have juvenile Huntington's disease (JHD).

 

To continue reading, go to DNA Science, where this post first appeared. 

Lung transplants can be lifesaving for patients with end-stage lung diseases such as cystic fibrosis, COPD, pulmonary fibrosis, sarcoidosis, and pulmonary hypertension. Wait times for a lung vary from days to years, depending on a complex set of circumstances. In the US, 1400 adults and children await lungs at any given time. Less than a third of them will get one.

 

Position on the wait list is based on several factors: medical urgency, compatibility with an available lung, distance from the donor hospital, and pediatric status, according to the United Network for Organ Sharing.

 

An easily tested indication of whether a person's body will accept a transplanted organ is the ABO blood type. It doesn't have to match between donor and recipient, but it must be compatible. The A and B antigens (cell surface molecules) are sugars that are attached to proteins and fats on a cell's surface. The blood type is a single-gene trait.

 

Canadian researchers have tested a way to strip donor lungs from type A individuals of the A antigens that make them type A, using enzymes. Denuding the lungs essentially creates an "ABO-agnostic organ" that could, theoretically for now, nestle into the chest of a person with any ABO blood type and not induce rejection. The idea has been around for awhile without much success, but using a new pair of enzymes, discovered in the human gut microbiome in 2019, seems to improve on past attempts. 

 

"The treatment described here could further expand the pool of universal donor organs from the current 55% (blood group O donors) to over 80%. This strategy may greatly improve access and fairness of organ allocation," Aizhou Wang and colleagues from the University of Alberta write in Science Translational Medicine. The strategy could be applied to organs other than lungs. More than 100,000 individuals in the US await organs.

 

To continue reading, go to DNA Science, where this post first appeared.

 

When Mark Twain wrote "Truth is stranger than fiction," he wasn't imagining people watching tales of an alien invasion and a pandemic unfold on their screens while hiding from a real pandemic. For a short span as 2021 became 2022, Apple TV+'s Invasion and HBOMAX's Station Eleven, each 10 episodes, briefly relieved reality. The first imagines planetary doom, while the second depicts humanity's recovery two decades after attack by a microscopic menace.

 

While thinking about both limited series a few days ago, I read a report in Nature that eerily evoked Mark Twain. It presents compelling evidence that SARS-CoV-2, the virus behind COVID-19, could change in one tiny but crucial part, in an instant, and transform itself into a pathogen perhaps worse than what we've already experienced. That truth would indeed be more terrifying than any fiction.

 

So here's a look at all three scenarios: two fiction, one not.

 

To continue reading, go to my blog DNA Science, where this post first appeared.

I have a special fondness for the yellow mealworm, Tenebrio molitor.

 

As a child, I fed the mealworm stage of this beetle to my pet chameleon.

 

As a teen, I babysat for a family that owned a pet shop. The house was filled with animals, and I was thrilled to be there. That is, until right before bedtime.

 

As I was trying to get the kids upstairs, a monkey grabbed a can, leaped atop a curtain rod, whipped the top off, and happily sprayed dozens, perhaps hundreds, of writhing, fat, pale mealworms all about the living room. It was great fun collecting them.

 

Then a few days ago I got a news release from Paris-based Ynsect. The company's goal: to farm massive numbers of yellow mealworms as food for humans. And I instantly remembered the creatures festooned around that long-ago living room.

 

Ynsect's good news was that the yellow mealworm's genome had finally been sequenced. Thank goodness! It was a tough one to crack.

 

Eating Mealworms

 

Farming yellow mealworms for food makes sense.

 

To continue reading go to my blog DNA Science.

Just as we thought Omicron was rolling across the US and into oblivion, a new "subvariant" has arrived and is, again, taking over. At the same time Moderna is announcing dosing of the first participant in its phase 2 study of an Omicron-specific booster. But Omicron's evolution wasn't unexpected – the World Health Organization's recent update cites four lineages of Omicron, dubbed BA.1 through BA.4.

 

"So it goes," to quote Kurt Vonnegut in Slaughterhouse Five. But that statement was in response to death among the Tralfamadorians – not the robust activity of a tiny virus.

 

It seems to me that the continual categorization of SARS-CoV-2 reflects the human urge to group, categorize, and name things to help us understand them. I think the situation is eventually going to dissolve into a continuum of genetic flux as the tango of mutation and selection continues. That's what nucleic acids do.

 

Since it still new days for Omicron 2.0, here's a snapshot:

 

WHAT WE KNOW 

 

To continue reading go to DNA Science, where this post first appeared.

In these days of the never-ending pandemic, other health problems continue to take a backseat. That's especially true for the 7,000 or so rare diseases that collectively affect only one in ten people, while the number of COVID fatalities in the US nears the million mark. 

 

Although some clinical trials for rare disease treatments have stalled, they'll resume once COVID settles into some version of endemicity. More than 60 cell and gene therapy FDA approvals are expected by 2030, according to the Massachusetts Institute of Technology's New Drug Delivery Paradigms Initiative. They range from RNA-based drugs to gene therapies to CRISPR fixes.

 

Rare diseases tend to strike the youngest. Clinicaltrials.gov hints at what's to come.

 

CRISPR is tackling sickle cell disease and thalassemia, while antisense technology is being tried for Duchenne muscular dystrophy. Searching for "gene therapy" brings up 5000 hits for this older approach, many targeting childhood diseases.

 

To continue reading, go to Genetic Literacy Project, where this post first appeared.