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Scientists Have Finally Found the Gene That Gives Cats Orange Fur

Slashdot reader sciencehabit writes: Most orange cats are boys, a quirk of feline genetics that also explains why almost all calicos and tortoiseshells are girls. Scientists curious about those sex differences—or perhaps just cat lovers—have spent more than 60 years unsuccessfully seeking the gene that causes orange fur and the striking patchwork of colors in calicos and tortoiseshells. Now, two teams have independently found the long-awaited mutation and discovered a protein that influences hair color in a way never seen before in any animal... Using skin samples collected from various cats, the researchers were able to hone in a mutation on the X chromosome that impacts how much of a protein a gene called Arhgap36 produces. Increasing the amount of the Arhgap36 in pigment producing cells called melanocytes activates a molecular pathway that produces a light red pigment. "Scanning a database of 188 cat genomes, Barsh's team found every single orange, calico, and tortoiseshell cat had the exact same mutation," writes Science magazine. "The group reports the discovery this month on the preprint server bioRxiv. A separate study, also posted to bioRxiv this month, confirms these findings... They also found that skin from calico cats had more Arghap36 RNA in orange regions than in brown or black regions." Arhgap36's inactivation pattern in calicos and tortoiseshells is typical of a gene on the X chromosome, says Carolyn Brown [a University of British Columbia geneticist who was not involved in either study], but it's unusual that a deletion mutation would make a gene more active, not less. "There is probably something special about cats." Experts are thrilled by the two studies. "It's a long-awaited gene," says Leslie Lyons, a feline geneticist at the University of Missouri. The discovery of a new molecular pathway for hair color was unexpected, she says, but she's not surprised how complex the interactions seem to be. "No gene ever stands by itself." Lyons would like to know where and when the mutation first appeared: There is some evidence, she says, that certain mummified Egyptian cats were orange. Research into cat color has revealed all kinds of phenomena, she says, including how the environment influences gene expression. "Everything you need to know about genetics you can learn from your cat."

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23andMe To Lay Off 40% of Its Workforce, Discontinue All Therapy Programs

The genetic testing company 23andMe announced it will cut 40% of its workforce, or 200 jobs, and halt the work on therapies it was developing. As the BBC notes, the company is fighting for survival after hackers gained access to personal information of millions of its users, causing the stock to crater by more than 70%. All seven of its independent directors also resigned in September, following a protracted negotiation with founder and Chief Executive Anne Wojcicki over her plan to take the company private. The BBC reports: On Tuesday, the company warned investors of "substantial doubt" about its ability to continue operating, as it reported that revenue had fallen to $44 million between July and September compared to $50 million in the same period last year. Losses fell to $59 million from $75 million. The job cuts are expected to lead to one-off costs of $12 million, including severance pay, for the plan that will result in savings of $35 million. "We are taking these difficult but necessary actions as we restructure 23andMe and focus on the long-term success of our core consumer business and research partnerships," Ms Wojcicki said. The company also said it is considering what to do with the therapies it had in development, including licensing or selling them. 23andMe is a giant of the growing ancestor-tracing industry. It offers genetic testing from DNA, with ancestry breakdown and personalised health insights. Its customers include famous names, from rapper Snoop Dogg to multi-billionaire investor Warren Buffett. The company was valued at roughly $3.5 billion when it listed on the Nasdaq stock exchange in 2021 and its share price peaked at $17.65. But they have since tumbled and are currently trading at less than $5.

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Researchers Develop New Method That Tricks Cancer Cells Into Killing Themselves

Our bodies divest themselves of 60 billion cells every day through a natural process called "apoptosis". So Stanford medicine researchers are developing a new approach to cancer therapy that could "trick cancer cells into disposing of themselves," according to announcement from Stanford's medical school: Their method accomplishes this by artificially bringing together two proteins in such a way that the new compound switches on a set of cell death genes... One of these proteins, BCL6, when mutated, drives the blood cancer known as diffuse large cell B-cell lymphoma... [It] sits on DNA near apoptosis-promoting genes and keeps them switched off, helping the cancer cells retain their signature immortality. The researchers developed a molecule that tethers BCL6 to a protein known as CDK9, which acts as an enzyme that catalyzes gene activation, in this case, switching on the set of apoptosis genes that BCL6 normally keeps off. "The idea is, Can you turn a cancer dependency into a cancer-killing signal?" asked Nathanael Gray, PhD, co-senior author with Crabtree, the Krishnan-Shah Family Professor and a chemical and systems biology professor. "You take something that the cancer is addicted to for its survival and you flip the script and make that be the very thing that kills it...." When the team tested the molecule in diffuse large cell B-cell lymphoma cells in the lab, they found that it indeed killed the cancer cells with high potency. They also tested the molecule in healthy mice and found no obvious toxic side effects, even though the molecule killed off a specific category of of the animals' healthy B cells, a kind of immune cell, which also depend on BCL6. They're now testing the compound in mice with diffuse large B-cell lymphoma to gauge its ability to kill cancer in a living animal. Because the technique relies on the cells' natural supply of BCL6 and CDK9 proteins, it seems to be very specific for the lymphoma cells — the BCL6 protein is found only in this kind of lymphoma cell and in one specific kind of B cell. The researchers tested the molecule in 859 different kinds of cancer cells in the lab; the chimeric compound killed only diffuse large cell B-cell lymphoma cells. Scientists have been trying to shut down cancer-driving proteins, one of the researchers says, but instead, "we're trying to use them to turn signaling on that, we hope, will prove beneficial for treatment." The two researchers have co-founded the biotech startup Shenandoah Therapeutics, which "aims to further test this molecule and a similar, previously developed molecule," according to the article, "in hopes of gathering enough pre-clinical data to support launching clinical trials of the compounds. "They also plan to build similar molecules that could target other cancer-driving proteins..."

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23andMe Is On the Brink. What Happens To All Its DNA Data?

The one-and-done nature of 23andMe is "indicative of a core business problem with the once high-flying biotech company that is now teetering on the brink of collapse," reports NPR. As 23andMe struggles for survival, many of its 15 million customers are left wondering what the company plans to do with all the data it has collected since it was founded in 2006. An anonymous reader shares an excerpt from the report: Andy Kill, a spokesperson for 23andMe, would not comment on what the company might do with its trove of genetic data beyond general pronouncements about its commitment to privacy. "For our customers, our focus continues to be on transparency and choice over how they want their data to be managed," he said. When signing up for the service, about 80% of 23andMe's customers have opted in to having their genetic data analyzed for medical research. "This rate has held steady for many years," Kill added. The company has an agreement with pharmaceutical giant GlaxoSmithKline, or GSK, that allows the drugmaker to tap the tech company's customer data to develop new treatments for disease. Anya Prince, a law professor at the University of Iowa's College of Law who focuses on genetic privacy, said those worried about their sensitive DNA information may not realize just how few federal protections exist. For instance, the Health Insurance Portability and Accountability Act, also known as HIPAA, does not apply to 23andMe since it is a company outside of the health care realm. "HIPAA does not protect data that's held by direct-to-consumer companies like 23andMe," she said. Although DNA data has no federal safeguards, some states, like California and Florida, do give consumers rights over their genetic information. "If customers are really worried, they could ask for their samples to be withdrawn from these databases under those laws," said Prince. According to the company, all of its genetic data is anonymized, meaning there is no way for GSK, or any other third party, to connect the sample to a real person. That, however, could make it nearly impossible for a customer to renege on their decision to allow researchers to access their DNA data. "I couldn't go to GSK and say, 'Hey, my sample was given to you -- I want that taken out -- if it was anonymized, right? Because they're not going to re-identify it just to pull it out of the database," Prince said. Vera Eidelman, a staff attorney with the American Civil Liberties Union who specializes in privacy and technology policy, said the patchwork of state laws governing DNA data makes the generic data of millions potentially vulnerable to being sold off, or even mined by law enforcement. "Having to rely on a private company's terms of service or bottom line to protect that kind of information is troubling -- particularly given the level of interest we've seen from government actors in accessing such information during criminal investigations," Eidelman said. She points to how investigators used a genealogy website to identify the man known as the Golden State Killer, and how police homed in on an Idaho murder suspect by turning to similar databases of genetic profiles. "This has happened without people's knowledge, much less their express consent," Eidelman said. Neither case relied on 23andMe, and spokesperson Kill said the company does not allow law enforcement to search its database. The company has, however, received subpoenas to access its genetic information. According to 23andMe's transparency report, authorities have sought genetic data on 15 individuals since 2015, but the company has resisted the requests and never produced data for investigators. "We treat law enforcement inquiries, such as a valid subpoena or court order, with the utmost seriousness. We use all legal measures to resist any and all requests in order to protect our customers' privacy," Kill said. [...] In a September filing to financial regulators, [23andMe CEO Anne Wojcicki] wrote: "I remain committed to our customers' privacy and pledge," meaning the company's rules requiring consent for DNA to be used for research would remain in place, as well as allowing customers to delete their data. Wojcicki added that she is no longer considering offers to buy the company after previously saying she was.

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