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Genetic Linkage

A Glimpse of the Ocean’s Twilight Zone Through Environmental DNA

Environmental DNA, or eDNA, gives researchers clues about which species are in that water–and their relative abundance. A WHOI-led study finds that changes in eDNA concentration reveal details of a creature's movement to and from the ocean twilight zone. Natalie Renier © Woods Hole Oceanographic Institution

To most people the Twilight Zone evokes memories of Rod Serling's iconic TV series of the 1950s and 1960s, or the less tantalizing recent reboot. But the Twilight Zone project at the Woods Hole Oceanographic Institution isn't a peek at William Shatner seeing a monster on an airplane's wing or Billy Mumy turning an annoying adult into a jack-in-the-box.


The twilight zone is a layer of the ocean that encircles the planet, from about 200 to 1,000 meters (650 to 3,300 feet) deep. It's also called the mesopelagic or midwater region. The zone is cold and dark, with flashes from bioluminescent organisms that shield them from predators. Pressure reaches 1,500 pounds per square inch. The biomass of fish in the twilight zone may exceed that of the rest of the ocean – but we know little about their distribution.


Residents of the twilight zone range from tiny bacteria and plankton, to fish, crustaceans, squid, and all sorts of gooey variations on the animal theme, like jellyfish and comb jellies. Quadrillions of bristlemouth fish, named for their spiny teeth, live in the zone. And we don't even know how many species have yet to be described. The animals in the twilight zone support the vast food web, moving carbon from the surface to the depths, regulating climate.


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

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Looking Back 20 Years After the Unveiling of the First Human Genome Sequence


I'm about to begin revising the 14th edition of my human genetics textbook. In normal times, I'd have amassed technical articles and case reports, as well as notes from meetings and interviews, choosing topics to add or ax and updating or replacing examples as the new edition takes shape.


But I haven't thought much about genetics in 18 months, instead obsessively reading, listening, and writing about COVID-19 and SARS-CoV-2, terms that didn't exist when the current edition was published in September 2019. The before time.


So much has changed since I published my first COVID article on January 23, 2020.


I'm relieved to focus once more on human genetics. A recent webinar from scientific publisher Elsevier, "20 Years of the Human Genome: From Sequence to Substance," has helped me get back on track and brought back memories.


Genetics Begat Genomics


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

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Leaping Lizards Regenerate Limbs, Thanks to CRISPR and Stem Cells

I've admired the cockroach's ability to regrow lost legs since learning about them while working on my PhD in developmental genetics ages ago. Cut off a roach's appendage, and soon signals from the exposed cells stimulate division of neighboring cells at the injury site. And out grows a new leg.


The signaling pathways of both embryonic development and regeneration are common to many animal species, and are therefore ancient. The genes in control have intriguing names: Grainy Head, Notch, Wingless, Sonic Hedgehog, and even Hippo.


I remember reading about elegant experiments that moved the cells at the interface of an amputation in a model organism, such as the cockroach poster-child for regeneration. When a researcher rotated the cells at a cut site, a turned-around limb unfurled.


Salamanders can regenerate limbs too. Back in graduate school in Thom Kaufman's lab at Indiana University, we had two pet Mexican axolotls from the developmental biology group upstairs. Sally and Gerry Mander lived in a large rectangular tank above the vials of fruit flies, happily swimming, as amphibians do. And if a bit of a leg broke off from crashing into the side, the salamander could regrow it.


Of course humans can't regenerate missing limbs, or even toes. Our closest relatives that can are lizards (reptiles, not amphibians).


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

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Antibody Cocktails Against Future COVID Variants, Thanks to Global Consortium CoVIC

"Give us your antibodies" might be the mantra of the The CoVIC Consortium, a global group of eclectic experts who introduce a "framework for antibody cocktail selection" in the journal Science. They haven't just predicted which antibodies, alone or in pairs, can "neutralize" viral variants, including some that haven't even evolved yet, but have actually tested the tango between antibodies and their targets. From 56 labs on 4 continents, CoVIC has amassed more than 350 monoclonal antibodies against the spike protein with which SARS-CoV-2 latches onto and enters our cells.


As I read the paper, I envisioned a war room, where strategists scrutinize giant, detailed maps as they move symbols of troops and weapons into position, planning assaults from different directions.

Antibodies 101


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

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How the Tabby Got Its Stripes

In 1902's Just So Stories, Rudyard Kipling famously explained how the leopard got his spots in what would today be deemed an extremely racist fable. Now Christopher Kaelin, Kelly McGowan, and Gregory Barsh, from the HudsonAlpha Institute for Biotechnology, have discovered how the tabby cat got its stripes: from a signal in the fetus. Their findings appear in Nature Communications.


"The genes that control simple color variation, like albinism or melanism, are the same in all mammals for the most part. However, the biology underlying mammalian color pattern has long been a mystery, one in which we have now gained new insight using domestic cats," said Barsh, who is editor-in-chief of PLoS Genetics.


To trace the origins of the common striped coat pattern, the team analyzed gene expression in single skin cells from fetuses collected from feral cats in trap-neuter-release programs being spayed – half of such females are pregnant. The work revealed a novel mechanism behind the origin of stripes, like Jackie's in the photograph.

Alan Turing's Idea


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

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New COVID Vaccines and More: A Perusal of ClinicalTrials.gov

The pandemic has upended many practices, among them peer review of technical medical and scientific articles.


Lax Peer Review + Social Media = Misunderstanding Science


Pre-COVID, the preprint sites bioRxiv.org ("bio-archive," founded in 2013) and medRxiv ("med-archive," founded in 2019) were mainly the province of science and medical journalists, and of course researchers. Preprints are technical papers that haven't yet been peer-reviewed, a process that can take months. Preliminary screens remove outrageous claims and check for plagiarism.


Until a few months into the pandemic, the warning on both sites not to report on these papers was hard to navigate to, but seasoned journalists knew to respect the conditions. With general assignment reporters suddenly covering a health care crisis that increasingly required knowledge of virology, immunology, and biotech, medRxiv and bioRxiv became great sources of news.


The disclaimer was moved to the opening page: "Preprints are preliminary reports of work that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information."


The warning hasn't helped.


Skipping peer review leads to confusion and the spread of misinformation, especially through the echo chamber of social media. "COVID Vaccine Preprint Study Prompts Twitter Outrage," for example, details the hoopla over a medRxiv preprint that, according to experts on the statistics used, grossly overestimates the risk of heart inflammation in male teens after taking the Pfizer-BioNTech vaccine. The yelling continues.


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

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How snake venom and a smoking cessation drug inspired a nasal spray that blocks COVID

A simple nasal spray that stops SARS-CoV-2 in its tracks? 


That could block the coronavirus in the nose, before it can travel down to the lungs or be coughed onto another person, perhaps becoming a powerful partner to vaccines and therapeutics, and easy to administer, store, and ship.


It "could allow us to reduce transmission and be able to have a quick response to outbreaks in certain areas of the world," said Jeffrey Nau, CEO of Oyster Point Pharma, based in Princeton NJ. The company recently announced repurposing of the smoking-cessation pill Chantix™ (varenacline), as well as a second molecule in the same class, simpinicline, each as nasal sprays against COVID. The FDA approved Chantix, a Pfizer product, in 2006. Today nearly 400 clinical trials are exploring other uses.


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

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Viewpoint: ‘The fetus is 1/25th of an inch’ — Texas abortion ban bungles the science on when human life begins

Now that early abortion is essentially banned and criminalized in Texas, with other states soon to debate similar legislation, it's important to reflect on one of the key issues raised by this new law: When does human life begin? Here is a background primer on human prenatal development. 


Understanding the biology is more important than ever, because the new Texas law is even more draconian than it appears to be at first blush, if that's even possible. It bans abortion at 6 weeks, but this cutoff is actually 4 weeks after conception when the fetus is 1/25th of an inch. Counting gestation from the last menstrual period is archaic, perhaps a holdover from the days when most obstetricians were male. And as anyone who has ever suspected she is pregnant knows, that reasoning is absurdly wrong. The "morning-after pill" is not a "two-weeks-later" pill. Nonetheless and unfortunately, much of the media have spread the meaningless 6-week factoid.


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

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New Target for Treating Huntington’s Disease: Controlling Runaway DNA Repair

When results of a clinical trial of a treatment for a rare disease are disappointing, feelings of despair among hopeful affected families resurface – especially if the only options are repurposed drugs. That's the case for Huntington's disease, an inherited neurological condition that affects about 30,000 people in the US, 16 percent of them children.


The HD community is reeling from two such setbacks. But a new approach to halting the runaway expansion of the HD gene (called HTT) that lies behind the illness may reignite hope. The strategy focuses not on the HTT gene itself, but on another with which it interacts – a gene that takes part in repairing damaged DNA. Results appear in Cell Reports.


An "Expanding Repeat" Disease


"Horse-and-buggy doctor" George Sumner Huntington first described HD in 1872.


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

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Returning to Live Music and How a Tiny Mutation Sent Delta All Over the World

Ann Wilson, of Heart fame.

A few nights ago I went to my first live music show since pre-pandemic times: Ann Wilson, the vocalist from Heart. She and her new band were at The Egg, a small ovoid-shaped venue in Albany, New York. We were in the third row, very close to the stage. All of us wore masks, and should a smidge of nostril emerge, an admonishing usher materialized instantly.


"It's great to see all of your smiling eyes!" joked Ann as she looked out at the limited-capacity audience. The performers were unmasked, Ann belting out the tunes, the guitarist next to her writhing in the throes of guitar-face, a malady in which a man playing a guitar assumes a simian visage, like Caesar in Rise of the Planet of the Apes caught deep in thought. Who knew that guitar-face would one day deter spread of a virus?


The show was amazing, full of rock classics, Heart tunes, and songs Ann wrote during lockdown. COVID restrictions just couldn't reign in long-ingrained concert behavior. And so we all belted out Dream On and Barracuda along with Ann and her band the Amazing Dawgs, our masks undulating to the beat, as I hoped fervently that none of the oldish audience would keel over from asphyxiation.


"An Experimental Pop Concert" Simulates Viral Spread


This morning I was happy to see a new paper, "The risk of indoor sports and culture events for the transmission of COVID-19," published in Nature Communications. Stefan Moritz and colleagues in Germany staged "an experimental pop concert" in August 2020 and found that good ventilation and "suitable hygiene measures" could limit virus-carrying aerosols and droplets.


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

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