Scientists Are Annoyed by This Pretty Big Flaw in The New DNA Emoji

They had one job (╯°□°)╯︵ ┻━┻

Unicode, the standards body that decides which emojis we all need on our phones and laptops, is finally adding a bunch of science emojis to the mix, including DNA – but there’s confusion over the style of the doodle that will eventually get used.

That’s because one of the samples shown by Unicode and Emojipedia shows DNA strands twisting to the left, as they do on the less common Z-DNA.

For the most common B-DNA structure, the one that is responsible for the origins of life, the twists should be right-handed.

The difference isn’t easy to spot at first, but it’s crucial in dictating the way the ladders of DNA are structured – it’s like going down a spiral staircase clockwise or anticlockwise, with one state the complete mirror image of the other.

dna emojis 2The new emoji, as imagined by Emojipedia.

Scientists love accuracy more than most, and so the new symbol sample has caused some frustrated reactions on Twitter, as Gizmodo reports.

Researchers have been quick to point out that Unicode and Emojipedia has gone for a spiral that twists in the wrong direction – or at least in the more obscure, less common direction.

However, the original draft of the new emojis for 2018 had the DNA emoji twisting in the correct way, so it seems there’s some confusion about which one will eventually get used.

dna emojis 3The original Unicode draft.

If you’re struggling to understand what we mean, point your index finger away from you, push out your hand and rotate your finger in a clockwise direction – you’re drawing DNA in the air. If you rotate your finger anticlockwise, you’re drawing Z-DNA.

All is not lost though: Apple, Google, Microsoft, Samsung and the rest all design their own emoji styles on top of whatever Unicode puts forward – that’s why emojis look different from device to device and app to app.

So there’s still hope these tech giants may not totally stuff up, and the final emoji designs on our devices will end up spiralling the right way.

In the meantime, scientists are busy pointing out the mistake. It may not matter too much in the grand scheme of things, but if you’re going to have a DNA emoji, you might as well make sure you get it right.

Other science-related emojis in the list of 157 new ones rolling out this year include a magnet, a test tube, and a petri dish (there’s a full list at Emojipedia). Before too long then, you should be able to have much more meaningful emoji-based science conversations with your friends.

DNA’s double-helical structure, which creates the twisting pattern, was discovered way back in 1953, with a right-handed spiral.

Since then scientists have wondered what caused that right-handed bias. One idea is that cosmic rays destroyed the left-handed ancestors of DNA on the early Earth, but at the moment we really don’t know for sure.

What we do know is that DNA should have a right-handed spiral, and flipping it over to show a mirror image is wrong – just as wrong as trying to exactly duplicate the actions of a right hand with a left hand.

This isn’t the first time this mistake has been made – the same error has appeared in textbooks and in graphics many times in the past – and we can’t get too angry when we’re getting skateboards and kangaroos added to our emoji vocabulary.

Now though, you should all know what to look out for. When the emojis eventually land on your phone, take a close look to see which way the DNA strand is twisted.


Debating Whether Next-Gen Sequencing Should Be Applied Universally in Metastatic Breast Cancer

Large list of potentially targetable genes, but what about outcomes?

Interest is great in genomically informed targeted therapy, with the goal of identifying genomic alterations that (1) are drivers of tumor growth and progression in individual patients to individualize therapy; and (2) are targetable directly or indirectly with approved or investigational agents.

But should all women diagnosed with metastatic breast cancer undergo next-generation sequencing (NGS)? The question was debated by two experts at the most recent San Antonio Breast Cancer Symposium.

Yes, said Funda Meric-Bernstam, MD, chair of Breast Cancer Research at the University of Texas MD Anderson Cancer Center in Houston. Genomic testing should be part of the clinical management, and should be considered in all patients with metastatic breast cancer and adequate performance status who have an interest in clinical trials.

A large list of genes are potentially targetable in breast cancer, she said, pointing to PIK3CA, Akt, HER2, TRK and other rare alterations.

Several PI3K inhibitors are in clinical trials to target PIK3CA, with “emerging hope in upcoming inhibitors such as alpelisib in combination with fulvestrant” in PIK3CA-altered advanced breast cancer, she said. Activating Akt mutations, usually E17K, are most commonly found in hormone receptor-positive breast cancer. Objective responses have been elicited with the catalytic inhibitor AZD5363 as monotherapy in patients with estrogen receptor-positive AktE17K-mutant breast cancer and is now being studied in combination with fulvestrant. Ipatasertib, another Akt inhibitor, combined with paclitaxel in patients with PIK3 pathway aberrations increased progression-free survival to 9.0 months, compared with 4.9 months with paclitaxel alone in a phase II study.

HER2 is a proven genetic target, Meric-Bernstam said, noting that some patients who are HER2-negative on initial screening are subsequently found to be HER2-positive on NGS of another or newer sample. “We’re not sure if this is genomic evolution or heterogeneity or technical issues with the first testing, and we’re not as sure of the therapeutic sensitivity in this context, especially if it represents heterogeneity.”

If the tumor is HER2 amplified on NGS, validation is not needed to institute HER2-directed therapy. If the tumor is not amplified on NGS, the patient may still have a lower level of amplification or overexpression. “There’s a lot of enthusiasm about exploring HER2 mutations as a target.”

A few years ago, activating HER2 mutations were discovered in HER2-negative breast cancer. In a series of 5,605 women with breast cancer who underwent genomic profiling, 10.6% had HER2 amplifications, 2.4% had HER2 mutations, and 0.7% had co-occurring HER2 amplification and mutation, she continued. A few agents have already been approved in the HER space, with neratinib being the most prominent.

A very rare alteration found in several tumor types including breast cancer is TRK fusions. As presented at the 2017 ASCO annual meeting, in a phase I/II basket trial of patients with TRK (tropomyosin receptor kinase) fusions, almost all patients treated with the pan-TRK inhibitor larotrectinib had an objective response, which proved durable. Meric-Bernstam explained that TRK fusions are pathognomonic in secretory breast cancer, which constitutes less than 1% of breast cancers. “Because they are rare in breast cancer, I am not going to advocate for TRK fusion testing across the board for this reason, but if you do have a secretory breast cancer patient, please do TRK fusion testing.”

Not performing NGS means that patients with rare alterations cannot be entered into genotype-selected clinical trials, she argued.

ESR1, another current clinically relevant mutation, is rarely found in primary breast cancer but is commonly found in the metastatic setting. Evidence suggests that as ESR1 mutations accumulate with further treatment, there may be some value in retesting or performing liquid biopsy. An ESR1 mutation may affect the choice of therapy; an improved PFS was obtained with the use of fulvestrant compared with exemestane in breast cancer patients with ESR1 mutations, which was not the case in the patient who were ESR1 wild type.

Outcomes Not Altered, Potential Pitfalls Remain

The debater taking the other side at the symposium, Fabrice André, MD, of Gustave Roussy Cancer Center in Villejuif, France, said the key question is whether in the context of routine practice, NGS should be considered for detection of somatic mutations. At least as of yet, he said, no such rationale exists.

At present, no drug approved for use in the treatment of breast cancer requires a genomic test, he reminded listeners. “The reason is because the current way of interpreting DNA sequencing is not useful in metastatic breast cancers, and is potentially deleterious.”

Although NGS has been able to detect alterations in PIK3CA, Atk1, ERBB2, and ESR1 for which objective responses have been observed with the use of targeted therapy in early phase study, their detection did not improve outcome. Progression-free survival in these studies ranged from 5 to 8 months, which was not superior to standard of care. Further, these alterations can be detected by polymerase chain reaction (PCR) assays on circulating tumor DNA, which would be less expensive than NGS, he said.

In the case of sensitivity to PD-1 inhibitors such as pembrolizumab, accelerated approval of the agent was granted in those patients with microsatellite instability-high or mismatch repair-deficient solid tumors. The companion diagnostic for this purpose is immunohistochemistry or PCR, not NGS, said André. “Keep in mind that breast cancer with microsatellite instability is extremely rare — something like 1% and mostly in triple-negative breast cancer.”

The largest commercially available NGS panel can detect about 300 targetable genomic alterations. The issue here is that large gene panels report targetable alterations that are not relevant or for which the wrong drug may be recommended. Therefore, NGS reports can be deleterious because they recommend ineffective therapy and deny effective therapies, he said — one illustration of the wrong target, for example, is fibroblast growth factor receptor (FGFR)1/2 amplification for which an FGFR may be recommended. Nogova et al reported an objective response rate of 0% in patients with breast cancer and FGFR1/2 amplification.

Two large clinical trials in which large gene panels were used had efficacy as the primary endpoint, and in both cases, the targeted drugs matched to the genomic alteration detected by NGS failed to improve PFS.

Finally, said André, the reporting of large panels of genes leads to major ethical, regulatory, and financial issues that have not yet been sorted out. For example, in comparing results obtained from different NGS vendors, the overlap in genomic alterations is sometimes poor. Another pitfall is that somatic genetic testing in patients with advanced cancer may also detect previously unrecognized pathogenic germline variants.

Furthermore, he said, with genomic testing the likelihood of finding a drug matched to a genomic alteration is low. Although sequencing is inexpensive, it generates additional cost for biopsies and potentially the off-label use of expensive drugs.

Nature, Meet Nurture

Single-cell analysis reveals dramatic landscape of genetic changes in the brain after visual stimulation

A “brainbow” of cerebral cortex neurons labeled with different colors.

“Nature and nurture is a convenient jingle of words, for it separates under two distinct heads the innumerable elements of which personality is composed. Nature is all that a man brings with himself into the world; nurture is every influence from without that affects him after his birth.” – Francis Galton, cousin of Charles Darwin, 1874.

Is it nature or nurture that ultimately shapes a human? Are actions and behaviors a result of genes or environment?

Variations of these questions have been explored by countless philosophers and scientists across millennia.

Yet, as biologists continue to better understand the mechanisms that underlie brain function, it is increasingly apparent that this long-debated dichotomy may be no dichotomy at all.

In a study published in Nature Neuroscience on Jan. 21, neuroscientists and systems biologists from Harvard Medical School reveal just how inexorably interwoven nature and nurture are.

Using novel technologies developed at HMS, the team looked at how a single sensory experience affects gene expression in the brain by analyzing more than 114,000 individual cells in the mouse visual cortex before and after exposure to light.

Their findings revealed a dramatic and diverse landscape of gene expression changes across all cell types, involving 611 different genes, many linked to neural connectivity and the brain’s ability to rewire itself to learn and adapt.

The results offer insights into how bursts of neuronal activity that last only milliseconds trigger lasting changes in the brain, and open new fields of exploration for efforts to understand how the brain works.

“What we found is, in a sense, amazing. In response to visual stimulation, virtually every cell in the visual cortex is responding in a different way,” said co-senior author Michael Greenberg, the Nathan Marsh Pusey Professor of Neurobiology and chair of the Department of Neurobiology at HMS.

“This in essence addresses the long-asked question about nature and nurture: Is it genes or environment? It’s both, and this is how they come together,” he said.

One out of many

Neuroscientists have known that stimuli—sensory experiences such as touch or sound, metabolic changes, injury and other environmental experiences—can trigger the activation of genetic programs within the brain.

Composed of a vast array of different cells, the brain depends on a complex orchestra of cellular functions to carry out its tasks. Scientists have long sought to understand how individual cells respond to various stimuli. However, due to technological limitations, previous genetic studies largely focused on mixed populations of cells, obscuring critical nuances in cellular behavior.

To build a more comprehensive picture, Greenberg teamed with co-corresponding author Bernardo Sabatini, the Alice and Rodman W. Moorhead III Professor of Neurobiology at HMS, and Allon Klein, assistant professor of systems biology at HMS.

Spearheaded by co-lead authors Sinisa Hrvatin, a postdoctoral fellow in the Greenberg lab, Daniel Hochbaum, a postdoctoral fellow in the Sabatini lab and M. Aurel Nagy, an MD-PhD student in the Greenberg lab, the researchers first housed mice in complete darkness to quiet the visual cortex, the area of the brain that controls vision.

They then exposed the mice to light and studied how it affected genes within the brain. Using technology developed by the Klein lab known as inDrops, they tracked which genes got turned on or off in tens of thousands of individual cells before and after light exposure.

The team found significant changes in gene expression after light exposure in all cell types in the visual cortex—both neurons and, unexpectedly, non-neuronal cells such as astrocytes, macrophages and muscle cells that line blood vessels in the brain.

Roughly 50 to 70 percent of excitatory neurons, for example, exhibited changes regardless of their location or function. Remarkably, the authors said, a large proportion of non-neuronal cells—almost half of all astrocytes, for example—also exhibited changes.

The team identified thousands of genes with altered expression patterns after light exposure, and 611 genes that had at least two-fold increases or decreases.

Many of these genes have been previously linked to structural remodeling in the brain, suggesting that virtually the entire visual cortex, including the vasculature and muscle cell types, may undergo genetically controlled rewiring in response to a sensory experience.

There has been some controversy among neuroscientists over whether gene expression could functionally control plasticity or connectivity between neurons.

“I think our study strongly suggests that this is the case, and that each cell has a unique genetic program that’s tailored to the function of a given cell within a neural circuit,” Greenberg said.

Goldmine of questions

These findings open a wide range of avenues for further study, the authors said. For example, how genetic programs affect the function of specific cell types, how they vary early or later in life and how dysfunction in these programs might contribute to disease, all of which could help scientists learn more about the fundamental workings of the brain.

“Experience and environmental stimuli appear to almost constantly affect gene expression and function throughout the brain. This may help us to understand how processes such as learning and memory formation, which require long-term changes in the brain, arise from the short bursts of electrical activity through which neurons signal to each other,” Greenberg said.

One especially interesting area of inquiry, according to Greenberg, includes the regulatory elements that control the expression of genes in response to sensory experience. In a paper published earlier this year in Molecular Cell, he and his team explored the activity of the FOS/JUN protein complex, which is expressed across many different cell types in the brain but appears to regulate unique programs in each different cell type.

Identifying the regulatory elements that control gene expression is critical because they may account for differences in brain function from one human to another, and may also underlie disorders such as autism, schizophrenia and bipolar disease, the researchers said.

“We’re sitting on a goldmine of questions that can help us better understand how the brain works,” Greenberg said. “And there is a whole field of exploration waiting to be tapped.”

New tool tracks down distant regulators of gene expression, upends expectations

Gene enhancers light up in distinctive patterns in different cell types in a fruit fly.

To put things simply, Harvard Medical School researcher Karen Adelman studies DNA “to see how genes get messed up in disease.”

Sometimes that means investigating mutations in the genes that make proteins. In sickle cell anemia, for example, a mutated gene builds improperly shaped hemoglobin that sticks together and reduces the ability of red blood cells to carry oxygen.

Adelman’s interest, however, lies in how otherwise normal genes are expressed—turned on or off—in the wrong amounts, at the wrong times or in the wrong tissues.

In the past few years, scientists have begun to appreciate how often these instructions come from DNA segments called enhancers located far from the genes they influence. Children can be born without a pancreas when a mutation in an enhancer disrupts the “go” signal to a gene 25,000 DNA bases away that is supposed to start growing the organ.

Mutations in these distant enhancers are increasingly being linked to many other diseases, including congenital heart diseases, type 2 diabetes, cancers and immunological disorders.

The problem? “There’s no good way to find those enhancers,” said Adelman, professor of biological chemistry and molecular pharmacology at HMS. “If something’s wrong, we don’t know where to look.”

That is now changing. Adelman and colleagues reported this week in Genes & Development that they repurposed a tool they developed in 2010, Start-seq, to generate maps of enhancers that are active in a given tissue type, disease or set of environmental conditions.

Adelman believes Start-seq will help researchers seeking the sources of disrupted gene expression as well as those trying to understand how enhancers work normally.

“How do enhancers give the right instructions in embryonic development and go wrong in cancer?” she said. “Not only is this stuff fascinating to explore, but we also need to answer these questions if we ever want to alter enhancers, such as to treat disease.”

Already, the team has made a surprising discovery that blurs the distinction between enhancers and the genes they regulate.

Who transcribes the transcribers?

Like the rest of her peers, Adelman was taught in school that enhancers simply send instructions, in the form of transcription machinery, to the genes they want to “switch on.” The machines copy the genes’ DNA into RNA and use that as a blueprint to build proteins.

But in 2010, researchers led by Michael Greenberg, the Nathan Marsh Pusey Professor and head of the Department of Neurobiology at HMS, discovered that enhancers in brain cells also spawn RNAs as they do their jobs—only these RNAs are tiny and short-lived, and they don’t code for proteins.

Since then, the community has debated: How common is this phenomenon? What purpose, if any, do the little RNAs serve?

Adelman and colleagues took advantage of the unique qualities of these RNAs to locate enhancers and get some answers.

“These RNAs are very different from the ones made at genes,” Adelman explained. “They’re generated, they fall off and then they’re quickly degraded. We developed a technique to find them when they’re still stuck to the enhancers.”

Rescued from the scrap heap

The Start-seq technique begins with cell samples. The researchers wash away long, mature RNAs and keep ones that are still stuck to the genome. They then pluck out short RNAs that have a chemical tag characteristic of RNA-construction machinery found at genes and enhancers.

Finally, the team sequences these RNAs, revealing where each came from on the genome.

The result: a list of just about every enhancer that was active at the time the sample was taken, along with their exact genetic sequences. While not perfect, Start-seq returns fewer false positives and false negatives than previous enhancer-detection methods, the authors found.

Poised to dive into the genetics and transcription dynamics that drive enhancers, the researchers can already answer one burning question: Around 95 percent of enhancers make RNA.

“This means transcription at enhancers and protein-coding genes have much more in common than we appreciated,” said Adelman. “Philosophically it makes sense—and it helps explain why protein-coding genes can act as enhancers—but it still turns things on their head quite a bit.”

The good news, she said, is that the vast knowledge scientists have gathered about control of protein-coding genes can now be applied to learning how enhancers work.

Community resource

The team is working to automate Start-seq so they can make it available to researchers throughout the HMS community and beyond.

The tool should enable people to search for overlaps between enhancer activity and genetic variants to tease out which variants might contribute to the biological phenomenon they’re studying, whether that is Parkinson’s disease or the differentiation of stem cells.

“We have plenty of neighbors who are hoping to identify relevant enhancers in their disease models,” Adelman said. “We hope to shine the flashlight on the right parts of the genome for them.”

Reconstructed adenoviruses found effective in cancer therapy

Genetic Flip Helped Organisms Go From One Cell to Many

Clockwise from top left: microscopic views of glands in frog skin, a sheep’s hoof, a tamarin’s skin and fish scales. 

Narwhals and newts, eagles and eagle rays — the diversity of animal forms never ceases to amaze. At the root of this spectacular diversity is the fact that all animals are made up of many cells — in our case, about 37 trillion of them. As an animal develops from a fertilized egg, its cells may diversify into a seemingly limitless range of types and tissues, from tusks to feathers to brains.

The transition from our single-celled ancestors to the first multicellular animals occurred about 800 million years ago, but scientists aren’t sure how it happened. In a study published in the journal eLife, a team of researchers tackles this mystery in a new way.

The researchers resurrected ancient molecules that once helped single-celled organisms thrive, then recreated the mutations that helped them build multicellular bodies.

The authors of the new study focused on a single molecule called GK-PID, which animals depend on for growing different kinds of tissues. Without GK-PID, cells don’t develop into coherent structures, instead growing into a disorganized mess and sometimes even turning cancerous.

GK-PID’s job, scientists have found, is to link proteins so cells can divide properly. “I think of it as a molecular carabiner,” said Joseph W. Thornton, an evolutionary biologist at the University of Chicago and a co-author of the new study

When a cell divides, it first has to make an extra copy of its chromosomes, and then each set of chromosomes must be moved into the two new cells. GK-PID latches onto proteins that drag the chromosomes, then attaches to anchor proteins on the inner wall of the cell membrane. Once those proteins are joined by GK-PID, the dragging proteins pull the chromosomes in the correct directions.

Bad things happen if the chromosomes head the wrong way. Skin cells, for example, form a stack of horizontal layers. New cells needs to grow in the same direction so skin can continue to act as a barrier. If GK-PID doesn’t ensure that the chromosomes move horizontally, the cells end up in a jumble, like bricks randomly set at different angles.

Previous studies have offered clues to how this important molecule might have evolved in the ancestors of animals. All animals (ourselves included) carry a gene sequence that’s very similar to the one producing GK-PID. But that gene encodes a different molecule with a different job: an enzyme that helps build DNA. The enzyme can be found even in other organisms, like fungi to bacteria.

Dr. Thornton and his colleagues wondered whether that enzyme and its cousin GK-PID shared some kind of evolutionary history.

First, they made a careful study of the different forms of GK-PID and the DNA-building enzyme in about 200 species. Then they worked out how the genes for these molecules must have mutated over the millenniums.

That analysis allowed the scientists to figure out the DNA sequence for GK-PID in the single-celled ancestors of animals — a gene that hasn’t been seen in hundreds of millions of years. Then Dr. Thornton and his colleagues did something even more amazing: They recreated those ancient molecules to see how they once functioned.

The ancestral version of GK-PID wasn’t a carabiner, the scientists found. Instead, it behaved like a DNA-building enzyme. That finding suggests that in the ancestors of animals, the gene for the enzyme was accidentally duplicated. Later on, mutations in one copy of the gene turned it into a carabiner.

But how many mutations did it take to transform the molecule? That’s the most remarkable part of the new study. The scientists altered the gene for the ancestral enzyme with the earliest mutations that evolved in it. They found it took a single mutation to flip GK-PID from an enzyme to a carabiner.

“Genetically, it was much easier than we thought possible,” Dr. Thornton said. “You don’t need some elaborate series of thousands of mutations in just the right order.”

The evolution of a molecular carabiner did not by itself give rise to the animal kingdom, of course. Other adaptations were needed to grow multicellular bodies. Dr. Thornton said that it might be possible to resurrect other ancestral molecules to figure out how those adaptations evolved, as well.

And if GK-PID is any guide, Dr. Thornton said, their evolution may have been surprisingly simple. A single mutation might have been enough to switch a molecule from one job to another.

Antonis Rokas, an evolutionary biologist at Vanderbilt University who was not involved in the study, agreed. “One of evolution’s most striking major innovations may be the end-product of a series of many minor innovations,” he said.

5 Children Have New Ears Grown From Their Own Cells in a World First

A group of five children in China have been given new ears – based on detailed 3D models and grown from their own cells – in a world first for this kind of treatment.

The kids, aged between 6 and 9, all had microtia, where the external part of the ear ends up deformed. In these cases the condition was unilateral, affecting only one side, so scientists were able to create high-resolution scans of their healthy ears to help grow replacement ones.

Now the team of tissue engineers and plastic surgeons has proved these techniques can work in human beings, they could offer a new lease of life for people living with microtia or other similar conditions.

“The results represent a significant breakthrough in clinical translation of tissue engineered human ear-shaped cartilage given the established in vitro engineering technique and suitable surgical procedure,” write the researchers in their published paper.

grow ears 2(EBioMedicine)

Cartilage cells called chondrocytes were harvested from the non-deformed ears by the scientists and then used to create a new ear for the other side of the head through a process of cell culturing.

With the help of computed tomography or CT scans of the healthy ears, a 3D-printed framework was created that the newly growing ear could expand into. Over time, natural cells replaced almost all of the artificial scaffolding.

Finally, the new ears were attached and reconstruction was completed, with some small cosmetic surgery procedures applied afterwards.

This kind of biological technology is actually several years old, but this is the first time it’s been used so effectively in human beings – the first of these implants was fitted 30 months ago, suggesting the long-term prospects are good.

“The delivery of shaped cartilage for the reconstruction of microtia has been a goal of the tissue engineering community for more than two decades,” Lawrence Bonassar, a biomedical engineering professor from Cornell University in New York who wasn’t involved in the study, told Jacqueline Howard at CNN.

“This work clearly shows tissue engineering approaches for reconstruction of the ear and other cartilaginous tissues will become a clinical reality very soon. The aesthetics of the tissue produced are on par with what can be expected of the best clinical procedures at the present time.”

Microtia rates are as high as 17.4 in 10,000 in some countries, affecting both hearing and self-confidence of the kids who are born with it.

Current treatments include fitting an artificial ear frame, or creating a new ear from rib cartilage, but this new approach beats them all in terms of both appearance and lessening the damage on the patient’s body.

“Surgeons have been toying with the idea of removing cartilage tissue from a patient and distilling that tissue into individual cellular components and then expanding those cellular components,” Tessa Hadlock from the Massachusetts Eye and Ear Infirmary, who wasn’t involved in the study, told CNN.

“The thing that is novel about this is that for the first time, they have done it in a series of five patients, and they have good long-term follow-up that shows the results of the ears that were grown from that harvested cartilage.”

However, there are some caveats to note – 2.5 years is a good stretch but the artificial parts of the ear haven’t yet fully degraded, so further monitoring up to 5 years is going to be needed before we’re sure this is a success.

What’s more, two of the cases showed slight distortions in the growth of the ears, which scientists will have to carefully monitor.

Nevertheless it’s a promising step forward for these procedures, as well as a potentially life-changing new option for those with microtia, if it becomes widely available.

“We were able to successfully design, fabricate, and regenerate patient-specific external ears,” write the researchers. “Further efforts remain necessary to eventually translate this prototype work into routine clinical practices.”

The research has been published in EBioMedicine.

My Grandmother Was Italian. Why Aren’t My Genes Italian?

As mother and daughter, Carmen and Gisele Grayson thought their DNA ancestry tests would be very similar. Boy were they surprised.

Maybe you got one of those find-your-ancestry kits over the holidays. You’ve sent off your awkwardly-collected saliva sample, and you’re awaiting your results. If your experience is anything like that of me and my mom, you may find surprises — not the dramatic “switched at birth” kind, but results that are really different from what you expected.

My mom, Carmen Grayson, taught history for 45 years, high school and college, retiring from Hampton University in the late 1990s. But retired history professors never really retire, so she has been researching her family’s migrations, through both paper records and now a DNA test. Her father was French Canadian, and her mother (my namesake, Gisella D’Appollonia) was born of Italian parents. They moved to Canada about a decade before my grandmother was born in 1909.

The author got her name from her Italian grandmother, Gisella D’Appollonia, but, according to two DNA ancestry tests, not a lot of genes.

Last fall, we sent away to get our DNA tested by Helix, the company that works with National Geographic. Mom’s results: 31 percent from Italy and Southern Europe. That made sense because of her Italian mother. But my Helix results didn’t even have an “Italy and Southern European” category. How could I have 50 percent of Mom’s DNA and not have any Italian? We do look alike, and she says there is little chance we were switched at birth.

We decided to get a second opinion and sent away to another company, 23andMe. We opened our results together and were just as surprised. This time, I at least had a category for southern Europe. But Mom came back as 25 percent southern European, me only 6 percent. And the Italian? Mom had 11.3 percent to my 1.6. So maybe the first test wasn’t wrong. But how could I have an Italian grandmother and almost no Italian genes?

Carmen Grayson’s 23andme results.

To answer this question, Mom and I drove up to Baltimore to visit Dr. Aravinda Chakravarti of the Johns Hopkins University School of Medicine and the Bloomberg School of Public Health and who has spent his career studying genetics and human health.

“That’s surprising,” he told us when we showed him the results. “But it may still be in the limits of error that these methods have.”

The science for analyzing one’s genome is good, Chakravarti says. But the ways the companies analyze the genes leave lots of room for interpretation. So, he says, these tests “would be most accurate at the level of continental origins, and as you go to higher and higher resolution, they would become less and less accurate.”

As in my case — the results got me to Europe, just not Italy.

Gisele Grayson’s 23andme results

My 23andMe test also showed less than 1 percent of South Asian, Sub-Saharan African, and East Asian & Native American. This, Chakravarti says, is likely true because the genetics of people on a continental level are so different, and it’s not likely South Asian is going to look like European. “Resolving a difference between, say, an African genome and an East Asian genome would be easy,” he says. “But resolving that same difference between one part of East Asia and another part of East Asia is much more difficult.”

I also learned that even though I got half my genes from Mom, they may not mirror hers.

We do have the genes we inherit — 50 percent from each parent. But Elissa Levin, a genetic counselor and the director of policy and clinical affairs of Helix, says a process called recombination means that each egg and each sperm carries a different mix of a parent’s genes.

“When we talk about the 50 percent that gets inherited from Mom, there’s a chance that you have a recombination that just gave you more of the northwest European part than the Italian part of your Mom’s ancestry DNA,” she says. That is also why siblings can have different ancestry results.

Carmen Grayson’s Helix/National Geographic results

The companies compare customers’ DNA samples to samples they have from people around the world who have lived in a certain area for generations. The samples come from some databases to which all scientists have access, and the companies may also collect their own.

“We’re able to look at, what are the specific markers, what are the specific segments of DNA that we’re looking at that help us to identify, ‘Those people are from this part of northern Europe or southern Europe or Southeast Asia,’ ” Levin says.

As the companies collect more samples, their understanding of markers of people of a particular heritage should become more precise. But for now, the smaller the percentage of a population within a continent that is in the database, the less certain they are. Levin says Helix chooses to not report some of those smaller percentages.

The 23andMe reports results with a 50 percent confidence interval — they’re 50 percent sure their geographic placement is correct. Move the setting up to 90 percent confidence, meaning your placement in a region is 90 percent certain, and that small 1.6 percent of my ancestry that is Italian disappears.

The ancestry tests also have to take into account the fact that humans have been migrating for millennia, mixing DNA along the way. To contend with that, the companies’ analyses involve some “random chance” as Levin puts it. A computer has to make a decision.

Gisele Grayson’s Helix/National Geographic results

And the ancestry companies have to make judgment calls. Robin Smith, a senior product manager with 23andMe, says their computers compare the DNA with 31 groups. “Let’s say a piece of your DNA looks most like British and Irish but it also looks a little bit like French-German,” he says. “Based on some statistical measures, we’d decide whether to call that as British-Irish or French-German, or maybe we go up one level and call it northwestern European.”

What does he think explains my case?

“It was a bit surprising,” he says. “But in looking at the fact that you have some southern European and some French-German, the picture became a little clearer to me.”

So, for now, my Italian grandmother doesn’t show up in these tests. No matter — Chakravarti, Levin and Smith all say let the results add to your life story. The DNA is just a piece of what makes you you.

Severe obesity linked to newly identified gene mutations

The Gene by Siddhartha Mukherjee review – intriguing and entertaining

Despite flaws, this lively and accessible history of the gene and its implications for the future is bursting with complex ideas
BGR4CT DNA sequence

In 2010, researchers launched a study, the Strong African American Families project, in one of the bleakest, most impoverished areas of rural Georgia, a place overrun by alcoholism, violence, mental illness and drug use. “Abandoned clapboard houses with broken windows dot the landscape,” Siddhartha Mukherjee tells us. “Crime abounds. Vacant parking lots are strewn with hypodermic needles. Half the adults lack a high school education and nearly half the families have single mothers.” You get the picture.

The scientists wanted to know how an individual’s genetic makeup might help or hinder their chances of surviving this grim background, and so began testing local families to determine which variant of a gene known as 5-HTTLRP they possessed. One, known as the short variant, had previously been linked to individuals prone to depression, alcoholism and anxiety. The other, the long variant, was associated with relative “normality”.

Sure enough, the scientists found that possessors of short variants were more likely to binge drink, use drugs and be sexually permissive. Combine a deprived background with a set of “bad” genes and your chance in life was doomed, it appeared. But the researchers went further, providing counselling for short-variant binge drinkers and long-variant “normals” to see how each group responded to help from others. They found the former group, while more prone to antisocial behaviour, was also more likely to react positively to counselling. That grim start to life was not quite so hopeless as it seemed. “It is as if resilience itself has a genetic core,” says Mukherjee in this broad-ranging guide to modern genetics and its impact on life.

The idea of a resilience gene has since taken root, leading psychologists to propose that susceptible short-variant children – the worst behaved but better at responding to counselling – be targeted for scarce and costly intervention. To his credit, Mukherjee is suspicious of the ethics of a scheme whereby an authority, having genotyped children in a particular area, could then be allowed to choose who is worthy of the attention of the best teachers and the most resources and who is not. Put that way, the notion looks unpleasant.

The trouble, says Mukherjee, is that we are going to encounter this sort of thing increasingly often as our ability to unravel the DNA of our fellow citizens becomes more powerful. And that refers not just to interventions we might make in a person’s upbringing but to those whose DNA we may be able to change. Already scientists are finding ways to alter the genetic makeup of children with harmful mutations including cystic fibrosis and muscular dystrophy. Soon, we will start to tackle more complex disorders – cancers or heart diseases – by altering or replacing entire groups of genes. “We have reached the stage where, as intelligent organisms, we are learning how to read the instructions for our own creation,” says Mukherjee. “Soon we will be ready to write our own instructions. In other words, we will be able to manipulate our own genetic future, snipping genes from embryos or adding new ones.”

A DNA strand
 Mukherjee is excellent on the ethical problems that will be presented by our growing ability to unpick the DNA of our fellow citizens.

The question is: who will choose what procedures are acceptable and who receives them? And what might be the unintended consequences? Illness might progressively vanish, but so might identity, if we tinker too much, says Mukherjee. Similarly, grief might be diminished but so might tenderness.

These are intriguing questions and, in trying to find answers, Mukherjee takes us on a journey that begins with the tribulations of his own family. He has two uncles and a cousin affected by schizophrenia and bipolar disorder; the question of whether he and his relatives are affected by a genetic predisposition to the conditions clearly concerns him. “Madness, it turns out, has been among the Mukherjees for at least two generations,” we are told. This is Mukherjee’s intimate history and it is touchingly related – though in truth it only forms an intermittent part of his narrative. The major part of The Gene is made up of a sweeping history of genetics that takes us from its dawn – with the garden pea experiments of Gregor Mendel, who revealed the existence of individual units of heritability – to modern gene-editing techniques, which allow scientists to alter or replace genes more or less at their leisure. It is an ambitious trip, to say the least.

Such efforts are welcome. This is a big book, bursting with complex ideas; without careful presentation, the reader would have struggled. Yet it is not without critics. An extract published last month in the New Yorker attracted strong censure from several biologists for misrepresenting the way our environments can affect the actions of genes, drawing a robust response from Mukherjee.

I have different qualms. For a start, I found the book’s priorities erratic. The key story of how DNA analysis showed Homo sapiens once interbred with our evolutionary cousins, the Neanderthals – the work of Swedish researcher Svante Pääbo – is dismissed in a few paragraphs while page after page is devoted to the work of US geneticist Dean Hamer, who in 1992 claimed to have found a “gay gene” that explained homosexuality in men – even though no gay gene has since been found, Mukherjee eventually admits. So why devote umpteen pages to the subject?

The latter stages of the narrative also present us with a rather irritating American triumphalism, as we progress through the late 20th and early 21st century to our modern mastery of the gene. Mukherjee tells us that, in 1980, David Botstein and his Massachusetts Institute of Technology colleagues were responsible for publishing the first proposal to use DNA variations to create a map of the human genome, a notion crucial to the subsequent launching of the Human Genome Project. In fact, Britain’s Walter Bodmer and Ellen Solomon had already outlined the idea in 1979, in the Lancet. The omission is slipshod.

Fortunately, these flaws do not detract seriously from an otherwise well-written, accessible and entertaining account of one of the most important of all scientific revolutions, one that is destined to have a fundamental impact on the lives of generations to come. The Gene is an important guide to that future.