Latest news with #geneticists
Forbes
02-06-2025
- General
- Forbes
Orange Fur Created By A Unique Mutation In Domestic Cats
A small deletion within a gene on the X-chromosome has unique effects upon cats' fur color, creating orange male tabbies and orange patches in female tortoiseshell cats. Tortoiseshell Cat. (Credit: Shutterstock, via Chris Kaelin) It was long predicted that the source of domestic cats' distinctive pumpkin-orange fur coloring was genetic and was produced by a gene on the sex-determining X-chromosome because 80% of orange cats are male — so the trait's mystery gene came to be known as 'sex-linked orange'. Male cats, like male humans, have an X- and a Y-chromosome. The genes on their lone X-chromosome are all expressed, giving rise to orange tabbies if they possess a copy of the orange fur color gene. Female cats have two X-chromosomes, one of which is randomly inactivated early in embryonic development on a cell-by-cell basis (figures 1 & 2), giving rise to tortoiseshell or calico fur color patterns. This pattern of inheritance suggests there is a gene that controls orange fur color on the X-chromosome, but identifying precisely which gene this is has eluded scientists for decades. Incidentally, white patches seen in calicos, known as 'piebalding', are not encoded by a gene on the X-chromosome. Figure 1: Graphical abstract, doi:10.1016/ 'Cats have lived commensally with humans around the world for thousands of years, giving humans plenty of time to select and preserve unusual colors and color patterns,' lead author of the Stanford study, geneticist Christopher Kaelin, told me in email. Dr Kaelin is a senior scientist in genetics at Stanford Medicine who has been studying the genetics of coloration and color patterns in mammals for more than two decades. Are cats the only domesticated mammal with a sex-linked fur color trait? 'Dogs also come in many color varieties. Some of the colors that are similar between dogs and cats are caused by different mutations in the same gene,' Dr Kaelin added. 'However, a sex-linked color trait has not been observed in dogs or other mammals, which suggests that orange cats could offer an opportunity to learn something new and insightful.' Dr Kaelin has worked alongside two of the Stanford study's co-authors – Greg Barsh and Kelly McGowan – on the genetics of coloration and color patterns for more than 25 years. They all started at Stanford, but Dr Barsh accepted a leadership position at HudsonAlpha 15 years ago, at a critical time when these researchers could adapt some of the emerging technologies being developed for human genomic science and apply them to genetic studies in domestic cats. 'Kelly [McGowan] and I also accepted positions at HudsonAlpha but remained at Stanford, where we were best equipped to pursue other aspects of our research,' Dr Kaelin explained in email. 'Kelly [McGowan] and I are currently affiliated only with Stanford, while Greg maintains affiliations with both institutions.' Additional collaborators on the Stanford study are based at Brown University, Auburn University, and at the National Cancer Institute. A second group of scientists, based at Kyushu University, Kindai University, Azabu University, The University of Tokyo and the National Institute of Genetics in Japan, independently discovered the same molecular mechanism underlying ginger-colored fur in domestic cats: a small deletion mutation on the cats' X-chromosome. The Kyushu team, whose work was largely crowdfunded by cat lovers around the world, published its research alongside the Stanford study in the peer-reviewed journal, Current Biology. 'These ginger and black patches form because, early in development, one X-chromosome in each cell is randomly switched off,' senior author of the Kyushu study, geneticist Hiroyuki Sasaki, a professor at Kyushu University, explained in a statement. 'As cells divide, this creates areas with different active coat color genes, resulting in distinct patches,' Professor Sasaki said. 'The effect is so visual that it has become the textbook example of X-chromosome inactivation, even though the responsible gene was unknown.' X-chromosome inactivation is a process whereby one copy of a female mammal's two X-chromosomes is rendered transcriptionally inactive. This phenomenon, sometimes known as Lyonization, was originally reported by British geneticist Mary Lyon who confirmed this theory in 1961 (ref). She discovered that female mammals' cells randomly silence one of the two X-chromosomes inherited from their parents. The inactivated chromosome can be seen under a microscope as a tiny dark Barr body compacted inside cells. Figure 2: X-Chromosome Inactivation (XCI) and cat fur colors. In cats, the X-chromosome contains a ... More gene controlling the orange/black pigmentation of the fur. If the two X-chromosomes of a female carry the same version of this gene, the coat of the adult cat will be of a single, unified color (either fully orange or fully black). However, if a female carries one X-chromosome with the orange variant and the other X-chromosome with the black variant, the mosaicism of XCI occurring during embryonic development will be visible in the color pattern of the adult cat's fur. In other words, the cat's fur is a mosaic of colors that reflects the random X-chromosome inactivation, that happens during early development. As a side note, and in contrast to the orange and black coloring, the presence of additional white patches in calico cats is not under the control of the X-chromosome. This condition, called 'piebalding', causes unpigmented skin and fur, and is commonly found in both XX and XY cats. (Credit: Image modified from '6-year old tortoiseshell cat," by Michael Bodega (public domain).) Originally, these two teams of scientists were investigating whether cats with orange fur were at a heightened risk for certain genetic disorders or health conditions, but along the way, they discovered that the cellular context (the tissue type, in this situation) of the gene's expression is what makes the difference. 'The orange mutation has not been linked to disease,' Dr Kaelin told me in email. 'In cats, the orange mutation occurs near a gene called Arhgap36 and activates it specifically in pigment cells.' The Arhgap36 gene is also present and active in humans. 'A related type of mutation has been identified in a human patient with a fatal disease that caused abnormal bone growth in areas where bone does not normally exist,' Dr Kaelin added in email. 'In that case, Arhgap36 is also activated, but in a different tissue type. Orange cats are spared that fate because the nature of the mutation appears to limit its activity to pigment cells.' Both Dr Kaelin and collaborators and the Kyushu study's team report that the missing section of DNA not only explains the unique sex-linked genetics of ginger fur in cats, but also points to an entirely new and so far unique mechanism for creating orange fur coloring in mammals. This discovery came after both Dr Kaelin and collaborators and members of the Kyushu collaboration compared the DNA from dozens of cats with and without orange fur. They found that cats with ginger fur color were missing a section of DNA within the Arhgap36 gene. This result of this mutation is that the Arhgap36 gene is more active than normal, leading to the production of pumpkin-orange fur pigment. Did this mutation for orange fur color arise just once? 'Orange cats are found all over the globe today, but our findings indicate that all orange cats can be traced back to a single orange (or tortoiseshell) cat,' Dr Kaelin replied to me in email. 'However, we still don't know when or where the original orange cat lived.' How long ago did this mutation arise? 'The wild progenitors of domestic cats are not orange, so we can infer that the mutation occurred during or after cat domestication. We know the mutation is old because calico cats are depicted in Chinese art dating to the 12th century. Identifying the orange mutation could help scientists who study ancient DNA look further back into prehistory for evidence of orange cats.' A Japanese woodblock print of calico cats in different poses and activities. Edo, Japan. NOTE: this ... More image was cropped from the original. (Credit: Utagawa Kuniyoshi (1798–1861); Japanese ukiyo-e painter / Public Domain.) Strangely, what seems to cause orange fur in cats isn't so much an 'orange gene' as it is an 'orange mutation' within a still-unknown gene, according to Dr Kaelin. Looking closer at the mutation, the researchers found that the deletion lies within a non-coding region of Arhgap36, so the resulting protein remains structurally unchanged. 'This is key,' Professor Sasaki explained. 'Arhgap36 is essential for development, with many other roles in the body, so I had never imagined it could be the orange gene. Mutations to the protein structure would likely be harmful to the cat.' 'The affected gene, Arhgap36, in orange cats is not typically a pigmentation gene,' Dr Kaelin explained in email. 'The unusual nature of the mutation represents a rare example of a gene acquiring a new function due to its accidental activation in a cell type where it is normally inactive. This process – where a gene acquires a new function – is thought to be important for evolution.' A change in genetic function or activity can have powerful consequences. For example, humans and chimpanzees share the same set of genes, but those genes act differently during development. 'Our study identifies a case in which a genetic change has a highly specific effect on gene activity, and understanding how this occurs will contribute to a broader understanding of gene regulation,' Dr Kaelin told me in email. Further analysis showed that high Arhgap36 activity is linked to reduced activity in many genes involved in melanogenesis, the process that produces pigment in skin and hair. Through an unknown mechanism, this change may alter pigment production away from dark eumelanin to lighter pheomelanin – orange. What other roles does this gene normally have? Is it active in neurogenesis or brain development? (I ask these questions because ginger cats are alleged to share a single brain cell between all members of the orange cat community worldwide.) 'Orange cats have their owners convinced that they are friendlier, more mischievous, and perhaps dimmer than other cats. This may all be true – or not,' Dr Kaelin told me in email. 'Rigorous scientific studies linking orange coat color to behavior have yet to be conducted. Arhgap36 is active in certain brain areas; however, in our study, we did not observe altered activity of Arhgap36 in those brain regions in the same way we observed altered activity in pigment cells.' Already, plans are underway to identify the orange gene's origins and additional cellular functions. 'One idea is to study ancient Egyptian cat paintings – or even to test DNA from mummified cats – to see if any cats back then were orange,' Professor Sasaki stated. 'It's ambitious, but I'm excited to try.' Another plan is to develop cat cell cultures to decipher the molecular function of Arhgap36. In addition to understanding molecular function of this gene in cat neurogenesis, this study may have medical implications for humans because this gene is also active in humans and is linked to conditions like skin cancer and hair loss. Hidehiro Toh, Wan Kin Au Yeun, Motoko Unoki, Yuki Matsumoto, Yuka Miki, Yumiko Matsumura, Yoshihiro Baba, Takashi Sado, Yasukazu Nakamura, Miho Matsuda & Hiroyuki Sasaki (2025). A deletion at the X-linked ARHGAP36 gene locus is associated with the orange coloration of tortoiseshell and calico cats, Current Biology | doi:10.1016/ Christopher B. Kaelin, Kelly A. McGowan, Joshaya C. Trotman, Donald C. Koroma, Victor A. David, Marilyn Menotti-Raymond, Emily C. Graff, Anne Schmidt-Küntzel, Elena Oancea & Gregory S. Barsh (2025). Molecular and genetic characterization of sex-linked orange coat color in the domestic cat, Current Biology | doi:10.1016/ Questions emailed to the senior authors of both studies, Hiroyuki Sasaki and to Gregory Barsh, and to the Kyushu study's co-lead author, Wan Kin Au Yeun, went unanswered. © Copyright by GrrlScientist | hosted by Forbes | Socials: Bluesky | CounterSocial | LinkedIn | Mastodon Science | MeWe | Spoutible | SubStack | Threads | Tumblr | Twitter
The Independent
16-05-2025
- Science
- The Independent
Scientists finally decode what makes orange cats so unique
Scientists have finally narrowed down on a long theorised elusive genetic mutation that makes orange cats so unique, unlike any other mammal. While the orange fur colour can be seen across mammals, including tigers, golden retrievers, orangutans and red-headed humans, only in domestic cats is the colouration linked to sex, appearing much more often in males. This pattern has pointed to an unknown "orange gene" on the X chromosome in cats but identifying this gene has eluded scientists for over a century. Now, a new study published in the journal Current Biology finally unravels this gene, explaining the peculiarity of ginger cat genetics. "Identifying the gene has been a longtime dream, so it's a joy to have finally cracked it," said Hiroyuki Sasaki, a geneticist and co-author of the study from Japan's Kyushu University. Any male cat with the mutation dubbed 'sex-linked orange' will be entirely orange due to a random deletion of a section of its DNA in the X chromosome. However, a female cat needs to inherit the genetic change on both of its X chromosomes to be entirely orange, which makes it a less likely occurrence. If a female cat inherits one orange and one black gene, they develop patchy or mottled coats that is seen in calicos and tortoiseshells. "These ginger and black patches form because, early in development, one X chromosome in each cell is randomly switched off," Dr Sasaki explained. "As cells divide, this creates areas with different active coat colour genes, resulting in distinct patches. The effect is so visual that it has become the textbook example of X-chromosome inactivation,' he said. In the study, researchers analysed DNA from 18 cats – 10 with orange fur and eight without. They found that all orange cats shared a specific deletion in the ARHGAP36 gene, while the non-orange cats did not. Scientists found that this pattern held true in 49 additional cats, including samples from an international cat genome database. However, until the discovery ARHGAP36 gene was thought to have no connection to pigmentation. "ARHGAP36 is essential for development, with many other roles in the body, so I had never imagined it could be the orange gene. Mutations to the protein structure would likely be harmful to the cat,' Dr Sasaki explained. Researchers then found ARHGAP36 gene activity in a cell type, called the pigment cell, in orange cats, where it's not normally expressed. The study found that this rogue expression of the ARHGAP36 gene in the cat pigment cells inhibits an intermediate step controlling coat colour. "Certainly, this is a very unusual mechanism where you get misexpression of a gene in a specific cell type," said Christopher Kaelin, another author of the study from Stanford University. Researchers suspect an altered expression of the gene in some other tissue might also affect behaviour. "There are not many scientific studies of the personality of orange cats," Dr Kaelin said. "For example, many cat owners swear by the idea that different coat colours and patterns are linked with different personalities. There's no scientific evidence for this yet, but it's an intriguing idea and one I'd love to explore further,' Dr Sasaki added. Scientists suspect that one reason orange cats have a reputation as 'friendly agents of chaos' could be due to most of them being male.
News.com.au
14-05-2025
- Health
- News.com.au
Groundbreaking new study links 25 genes to Obsessive Compulsive Disorder
A new study has found 25 genes believed to cause Obsessive Compulsive Disorder. More than 50,000 people with the condition had their genetic data compared to those who did not.
CNN
07-05-2025
- Science
- CNN
How South Korea's legendary female free divers evolved for a life underwater
Sign up for CNN's Wonder Theory science newsletter. Explore the universe with news on fascinating discoveries, scientific advancements and more . CNN — An island 50 miles (80 kilometers) off the southern tip of the Korean Peninsula is home to a unique and celebrated community of women: the Haenyeo. These women dive year-round off Jeju Island, collecting sea urchin, abalone and other seafood from the ocean floor, descending as much as 60 feet (18 meters) beneath the surface multiple times over the course of four to five hours each day. They dive throughout pregnancy and well into old age, without the help of any breathing equipment — just a wet suit. 'For thousands of years, we think, they've been doing this incredible, matrilineal thing, where they learn from the mother how to dive at a very young age. They go out in these collectives, and that's what they do. They dive,' said Melissa Ann Ilardo, a geneticist and assistant professor in biomedical informatics at the University of Utah. 'They're spending really an extraordinary percentage of their time underwater.' Ilardo, along with colleagues in South Korea, Denmark and the United States, wanted to understand how the women manage this incredible physical feat. Specifically, the researchers wondered whether the divers have unique DNA that allows them to go without oxygen for so long or if that ability is the result of a lifetime of training — or a combination of the two. The findings of their investigation, published in the scientific journal Cell Reports on May 2, uncovered unique genetic differences the Haenyeo have evolved to cope with the physiological stress of free diving. It's a discovery that could one day lead to better treatments for blood pressure disorders, researchers say. 'It's a beautiful island, like sometimes they call it the Hawaii of Korea. There's this coastline everywhere that's rich with great resources, so you can imagine any population living in a place like that of course you would want to take advantage of it,' Ilardo said. Diving has been part of Jeju culture for many years. It's unclear at what point it became a women-only activity, but theories include a tax on male divers or a shortage of men, Ilardo said. Still, diving is so integral to Jeju's population that the shortening of words characteristic of the Jeju language is attributed to the need for divers to communicate quickly, according to the new study. However, the practice is dying out. Young women are no longer continuing this matrilineal tradition; the current group of Haenyeo divers, with an average age of around 70 years, may represent the last generation, the researchers noted in the study. For their research, Ilardo and her colleagues recruited 30 Haenyeo divers, 30 non-diving women from Jeju and 31 women from the South Korean mainland. The average age of the participants was 65. The researchers compared participants' heart rates, blood pressure and spleen sizes and sequenced their genomes — a detailed genetic blueprint — from blood samples. The study's biggest challenge was safely replicating the physical stress of being underwater for relatively long periods for participants with no diving experience, Ilardo noted. The researchers solved this problem by conducting simulated dives, during which participants held their breath while submerging their faces in cold water. 'We would have loved to collect these measurements from everyone in the open ocean, but obviously you can't ask 65-(year-old), 67-year-old women who have never dived before in their lives to hop in the water and hold their breath and dive,' Ilardo said. 'Fortunately, if you hold your breath and put your face in a bowl full of cold water, your body responds as if you're diving. And that's because the nerve that stimulates the mammalian dive reflex goes through your face,' she said. When you feel the cold water combined with the breath hold, 'your body says, 'oh I'm diving': So your heart rate slows down, your blood pressure increases and your spleen contracts,' she added. The team's analysis revealed that the participants from Jeju — both divers and non-divers — were more than four times more likely than mainland Koreans to have a genetic variant associated with lower blood pressure. 'Your blood pressure increases as you dive. Their (Jeju residents') blood pressure increases less,' Ilardo explained. The researchers believe the trait may possibly have evolved to keep unborn children safe because the Haenyeo dive throughout pregnancy, when high blood pressure can be dangerous. The team also found that the Jeju participants were more likely to have a genetic variation previous research has linked to cold and pain tolerance. However, the researchers did not measure the participants' ability to withstand low temperatures, so they can't say for sure whether the variant may be important for the Haenyeo's ability to dive year-round. 'Throughout winter they're diving when it's snowing, and up until the 1980s, they were doing that in cotton with no protection at all. There's a lot more that we need to explore and find the answers to,' Ilardo said. The Haenyeo's diving prowess didn't come down to genetics alone. The study also found that the female divers had a slower heart rate than non-divers during the tests — a factor that would help them to conserve oxygen during a dive. 'It was quite dramatic. Actually, their heart rate dropped about 50% more over the course of the dive than the control (participants). We know that it's because of training, because it's something that we only saw in the Haenyeo,' Ilardo said. Ilardo's previous work involving free diving communities known as the Bajau in Sulawesi, Indonesia, had revealed genetic adaptations that allowed the Bajau to go for longer periods without oxygen, resulting in unusually large spleens. However, while Jeju residents did, on average, have a larger spleen than the study participants from mainland South Korea, the effect wasn't significant when other factors like age, height and weight were accounted for, she said. The genetic variant that the study identified in the Jeju residents associated with lower blood pressure should be explored further, according to Ben Trumble, an associate professor at Arizona State University's School of Human Evolution and Social Change. 'Those with this gene had more than a 10% reduction in blood pressure compared to those who don't have this gene, that's a pretty impressive effect,' said Trumble, who wasn't involved in the study. 'Genes code for proteins, and if we can figure out which changes in proteins impact blood pressure, we could potentially create new drugs,' Nearly all medical and genetic studies are conducted in industrialized populations, usually in urban city centers, making Ilardo's approach particularly valuable, Trumble added. 'Almost everything we know about what is 'normal' when it comes to health is from these sedentary urban populations. However, for 99.9% of human history, we were hunter-gatherers,' he said. 'Natural selection optimized our bodies under very different selective pressures than those we face today.' Ilardo said she hopes to continue to study Jeju's female divers and get a deeper understanding of the medical implications. 'This study raises more questions than it answers, but first and foremost, it shows these women are extraordinary,' she said. 'There's something biologically different about them that makes them extremely special, no matter how you characterize it, and what they do is unique and worth celebrating.'
