Genetic War That Decides Sex

X vs. Y: The Hidden Genetic War That Decides Sex

Scientists have discovered how genes on X and Y chromosomes fight for control over sperm, influencing whether more male or female offspring are born—and they’re studying this battle by recreating it in yeast. Deep within the cells of mice, a genetic arms race is unfolding between X and Y chromosome genes, battling for dominance in sperm.

Researchers have now discovered how these gene families compete by hijacking key proteins to boost the odds of producing male or female offspring. Using an ingenious yeast-based model, scientists are unraveling the molecular chess game that helps maintain the evolutionary balance of the sexes.

What Is Evolutionary Fitness?

In evolutionary terms, fitness is defined as an organism’s ability to survive and reproduce its genes into the next generation. Genes influence fitness, sometimes competing against each other within an organism. This competition, or arms race, is typically hard to observe–except when the genes in question live on the X and Y chromosomes, which determine the sex of offspring in mammals. In mice, this arms race can result in broods that have more males or females.

Cracking the Code of Sperm Competition

A study from University of Michigan researchers has uncovered the mechanism behind the arms race for mouse X and Y bearing sperm to fertilize an egg, analogous to space races to reach the moon.

“The X-carrying or Y-carrying sperm that gets there first is the one that successfully fertilizes the egg,” said Martin Arlt, Ph.D., associate research scientist in the Department of Human Genetics.

“If there were genes conferring benefits to X-bearing sperm, you would start to see more female offspring and vice versa. Yet we see a close to 50-50 split,” said Arlt, also the first author on the study.

“Over evolutionary time, the 50-50 split is the optimal ratio for a species with minor shifts potentially leading to loss of the species.”

Co-Adaptation on the X and Y Chromosomes

The sex-ratio balance is maintained as genes on the X and Y chromosomes co-adapt to keep each other in check. How this happens has been a mystery, as sperm cannot be grown in a lab. The U-M team found a unique solution, moving the X-linked Slxl1/Slx and Y-linked Sly gene families from mouse and putting them into yeast.

“We introduced each player in the competition into yeast to better understand how they work. Then we combined them to see how they interact and compete with one another.”
Competing for Control: The Role of Spindlins

In doing so, they discovered that the proteins encoded by Slxl1/Slx and Sly that affect sperm fitness appeared to compete for proteins called Spindlins, which influence gene expression. These proteins compete against each other for binding; the more of the X-linked gene family proteins that bind, the more X-carrying sperm that result and vice versa.

A Recent Evolutionary Innovation

“These proteins are relatively new innovations in evolutionary time, only a few million years old, well after humans diverged from chimps,” said Jacob Mueller, Ph.D., associate professor of human genetics and senior author on the paper.

“Spermatogenesis can and does occur fine without Slxl1/Slx and Sly, yet these genes have persisted in mice by integrating themselves into a system that is very important for the species. We have evidence that these arms races are happening over and over again in different species at different times.”

What’s Next in Gene Competition Research

In the future, the team plans to use the yeast model system to explore the evolution of the X/Y arms race and other competitive genes.

genetic war, sex determination, SRY gene, X chromosome, Y chromosome, transcription factors, sexual differentiation, gonadal development, gene expression, epigenetics, hormonal signaling, intersex, androgen insensitivity, turner syndrome, genomic imprinting, developmental biology, CRISPR, genome sequencing, comparative genomics, molecular biology

#GeneticWar, #SexDetermination, #SRYgene, #Xchromosome, #Ychromosome, #TranscriptionFactors, #SexualDifferentiation, #GonadalDevelopment, #GeneExpression, #Epigenetics, #HormonalSignaling, #Intersex, #AndrogenInsensitivity, #TurnerSyndrome, #GenomicImprinting, #DevelopmentalBiology, #CRISPR, #GenomeSequencing, #ComparativeGenomics, #MolecularBiology

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Rare virus that killed Gene

Rare virus that killed Gene Hackman's wife linked to three deaths in California

A rare virus that killed actor Gene Hackman’s wife in February has been linked to the deaths of three people in California. Hantaviruses are a group of viruses primarily spread through the urine, droppings or saliva of deer mice.

A rare virus that killed actor Gene Hackman's wife in February has been linked to the deaths of three people in California. Officials in Mono County, located between the crest of the Sierra Nevada mountains and the California-Nevada border, announced in a news release Thursday that a third person had died from a hantavirus in the small town of Mammoth Lakes so far this year.

Hantaviruses are a group of viruses primarily spread through rodent urine, droppings or saliva and cause fevers, muscle aches and shortness of breath, with a nearly 40% mortality rate, according to the Centers for Disease Control and Prevention. Deer mice, which are common in Mono County, are common carriers of it and Mono County officials said they suspect their numbers are higher this year.

Tom Boo, the public health officer for Mono County, said that it was "tragic and alarming" that three people have died from the Hantavirus Pulmonary Syndrome, the disease associated with the virus, in a short period of time. "We don't have a clear sense of where this young adult may have contracted the virus. The home had no evidence of mouse activity," Boo said.

"We observed some mice in the workplace, which is not unusual for indoor spaces this time of year in Mammoth Lakes. We haven't identified any other activities in the weeks before illness that would have increased this person's exposure to mice or their droppings."

Boo noted that, as far as officials know, none of the three victims had engaged in the types of activities that typically lead to exposure to a hantavirus, like cleaning out a poorly ventilated room with an abundance of mouse waste.

"These folks may have been exposed during normal daily activities, either in the home or the workplace. Many of us encounter deer mice in our daily lives and there is some risk," he said. "We should pay attention to the presence of mice and be careful around their waste."

He encouraged local residents to be vigilant with preventative measures against rodent activity, including setting out snap traps and sealing any gaps in a home larger than the width of a pencil, among other measures. The news came weeks after it was revealed that Betsy Arakawa, Hackman's wife, had died at their home in New Mexico from the virus.

Arakawa and Hackman were both found dead at their Santa Fe home in February, but Hackman tested negative for the hantavirus. His death was determined by an autopsy to have been caused by "hypertensive and atherosclerotic cardiovascular disease with Alzheimer's disease as a significant contributory factor."

zoonotic diseases, emerging pathogens, viral hemorrhagic fevers, orphan viruses, viral mutations, host-pathogen interaction, cross-species transmission, viral reservoirs, virome studies, viral diagnostics, viral latency, biosafety level 4, viral sequencing, phylogenetic analysis, neglected tropical diseases, immune evasion, antiviral resistance, outbreak surveillance, viral epidemiology, public health preparedness

#RareVirus, #EmergingPathogens, #ZoonoticThreats, #VirusResearch, #OutbreakAlert, #VirologyMatters, #InfectiousDiseases, #ViralGenomics, #NeglectedViruses, #BiosafetyLevel4, #OneHealth, #GlobalHealthSecurity, #PandemicPreparedness, #MutatingViruses, #VirusSurveillance, #PathogenHunting, #TropicalMedicine, #SilentEpidemics, #HostPathogen, #ViralThreats

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Chromosome abnormalities

Chromosome abnormalities found in healthy breast tissue

Epithelial cells, which line many body surfaces, can transform into several types of cancer. These transformed cancer cells often have an abnormal number of chromosomes, either more or less than the standard 23 pairs of chromosomes. This condition, called aneuploidy, is a hallmark of cancer, and it is commonly seen in breast cancer.

A few studies in recent years have used advanced genetic sequencing techniques to detect small numbers of aneuploid cells in normal body tissues, including the brain, colon, liver, lymphocytes, and sperm. But the significance of these rare aneuploid cells in healthy tissues is not well understood.

A research team led by Dr. Nicholas Navin of the University of Texas MD Anderson Cancer Center set out to learn about the prevalence and potential impact of aneuploid epithelial cells in normal breast tissue. They analyzed breast epithelial cells from 49 women who were undergoing breast reduction surgery. All of the women were healthy and had no signs of breast cancer. Their ages ranged from 18 to 63.

The researchers used a combination of advanced sequencing techniques to assess chromosome additions and deletions in more than 83,000 breast epithelial cells from these women. They then compared their findings to previously gathered data from women who had invasive breast cancer. Study results appeared in Nature on November 20, 2024.

The researchers found that all of the 49 healthy women harbored rare aneuploid epithelial cells in their breast tissue. A median of about 3% of the tested cells in each woman were aneuploid. The number of aneuploid epithelial cells in each woman tended to increase with age. Most of these abnormal cells (median more than 80%) had undergone significant chromosomal changes, many of which are seen in invasive breast cancers.

The findings suggest that most healthy women have low levels of aneuploid cells in their breast tissues. Additional studies are needed to determine if increased levels of these rare cells raise the risk for future breast cancer. In addition, the researchers note that their findings might also be applicable to other organs and tissues that contain epithelial cells.

“We’ve always been taught that normal cells have 23 pairs of chromosomes. But that appears to be inaccurate because every healthy woman that we analyzed in our study had irregularities, bringing up the very provocative question about when cancer actually occurs,” Navin says. “This has pretty big implications not just for the field of breast cancer, but potentially for multiple cancer types.”

congenital disorders, genetic mutations, chromosomal abnormalities, birth defects, developmental delay, neurological disorders, metabolic disorders, structural anomalies, rare diseases, prenatal diagnosis, hereditary conditions, gene expression, syndromic features, phenotype variation, molecular abnormalities, clinical manifestations, diagnostic imaging, pathophysiology, cellular dysfunction,

#abnormalities, #geneticdisorders, #birthdefects, #neurologicalabnormalities, #congenitaldisorders, #chromosomalanomalies, #raredisease, #developmentaldelay, #prenataldiagnosis, #moleculargenetics, #clinicalresearch, #genemutation, #phenotypevariation, #medicalgenetics, #structuraldisorders, #epigenetics, #diagnosticimaging, #metabolicdisorders, #healthresearch, and #cellulardysfunction

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Genetic Susceptibility

High muscle strength can prevent type 2 diabetes regardless of genetic susceptibility

Researchers from the School of Public Health, LKS Faculty of Medicine of the University of Hong Kong (HKUMed) conducted a large-scale epidemiological study to explore the potential health benefits of high muscle strength in preventing type 2 diabetes (T2D) across varying levels of genetic risk.

The study found that higher muscle strength was associated with over 40% lower risk of T2D, regardless of genetic susceptibility to T2D. The study highlights the importance of maintaining or improving muscle strength as a key strategy for preventing T2D. The findings were published in BMC Medicine.

T2D is one of the most common chronic metabolic disorders, and it is associated with an increased risk of various complications, including heart disease, stroke, high blood pressure, and narrowing of blood vessels. It is characterized by elevated blood sugar levels, also known as hyperglycemia, due to insulin resistance and impaired insulin secretion.

Evidence suggests that around 10% of the global population is affected by T2D, therefore, preventing T2D is a significant global public health concern. T2D can be caused by the interplay between non-modifiable genetic traits and modifiable lifestyle factors. Muscle strength is an important aspect of muscular fitness, and it has been found to be associated with lower risk of various cardiometabolic diseases including T2D.

However, it remains unclear whether improving muscle strength should be considered a T2D prevention strategy in individuals with varying levels of genetic susceptibility to T2D, particularly those with high genetic susceptibility to T2D.

Research methods and findings

The research utilized data of 141,848 white British individuals without baseline T2D from the UK Biobank, an ongoing prospective cohort of over 500,000 U.K. adults which includes extensive genotype and phenotype information. Muscle strength was assessed in the form of grip strength. Genetic risk of T2D was estimated based on 138 known genetic variants for T2D.

The participants were followed up for more than seven years. During the follow-up period, 4,743 new T2D cases were identified. The findings indicated that, compared with low muscle strength, individuals with high muscle strength was associated with a 44% lower relative risk of developing T2D, even after taking into account T2D genetic risk as well as other risk factors.

Moreover, the research team observed evidence of an interaction between muscle strength and genetic susceptibility to T2D, suggesting that muscle strength may play a role in modifying the impact of genetic risk to T2D onset. The findings further revealed that individuals at high genetic risk of T2D but with high muscle strength could have a lower absolute risk of T2D, compared with those at low or medium genetic risk but with low muscle strength.

This study uncovered the first-ever prospective associations between muscle strength, genetic susceptibility to type 2 diabetes, and the risk of developing the disease. "The findings emphasize the crucial role of maintaining or enhancing muscle strength as a key strategy for preventing T2D in middle-aged and older adults, regardless of their genetic risk levels and including those at high genetic risk.

"We believe that these results offer novel insights into the significant impact of higher muscle strength on metabolic health," said Dr. Wang Mengyao, from the School of Public Health at HKUMed, the first author of this study.

"This study highlights the significance of Biobank studies in examining the interaction between exposures and genetics in influencing the risk of T2D. Further research utilizing ethnic-specific Biobank studies is needed to determine if these findings are applicable to other populations, such as East Asians," said Professor Ryan Au Yeung, Assistant Professor from the School of Public Health at HKUMed, a co-author of this study.

"Individuals in middle-to-late life are at increased risk of type 2 diabetes. However, our study has demonstrated the potential roles of high muscle strength in preventing the future risk of developing type 2 diabetes not only in all individuals, but also in individuals with high genetic predisposition to type 2 diabetes.

"Our study supports the current public health guidelines which suggest that adults should engage in muscle-strengthening activities for at least two days per week from a disease prevention perspective," added Professor Youngwon Kim, from the School of Public Health at HKUMed, the corresponding author of the study.

Genetic disorder, inherited disease, mutation, DNA sequencing, chromosomal abnormality, gene therapy, rare disease, hereditary condition, genetic screening, precision medicine, Mendelian disorder, genomic research, personalized treatment, epigenetics, autosomal recessive, autosomal dominant, next-generation sequencing, genetic counseling, gene expression, pathogenic variant

#GeneticDisorder, #InheritedDisease, #Mutation, #DNASequencing, #ChromosomalAbnormality, #GeneTherapy, #RareDisease, #HereditaryCondition, #GeneticScreening, #PrecisionMedicine, #MendelianDisorder, #GenomicResearch, #PersonalizedTreatment, #Epigenetics, #AutosomalRecessive, #AutosomalDominant, #NextGenSequencing, #GeneticCounseling, #GeneExpression, #PathogenicVariant

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Kids with Down syndrome

Kids with Down syndrome can live 'abundant lives,' dad tells Fox News contributor

Fox News contributor Tom Shillue speaks to the dad of a child with Down syndrome on World Down Syndrome Day. Each year on March 21, World Down Syndrome Day (WDSD) marks a global day of awareness and education about the genetic condition.

The goal is to "help people understand and support those with Down syndrome better," according to the initiative's website. WDSD has been officially observed by the United Nations since 2012. On Friday, Fox News contributor Tom Shillue headed to Times Square in New York City to speak with New Yorkers about their awareness of WDSD. (See the video at the top of this article.)

Shillue spoke with Daniel Schreck, chairman of the Jérôme Lejeune Foundation, a global nonprofit focused on research and advocacy for people with genetic intellectual disabilities. Schreck also has a daughter with Down syndrome. When asked about common fears or misunderstandings about the condition, Schreck spoke of the perceived limitations. "I think the most important thing is that if you have Down syndrome, just like any other disability, you can live an abundant life and there's nothing to be afraid of," he said.

FAMILY OF CHILD WITH DOWN SYNDROME WENT FROM SHOCK TO GRATITUDE: ‘LOST THE AIR IN MY CHEST’

"Plus, people with Down's syndrome are the happiest people you've ever met. So there's nothing to be afraid of." The date of WDSD, the 21st day of the third month, was chosen to commemorate the triplication (trisomy) of the 21st chromosome, which is the cause of Down syndrome. Down syndrome is the most common chromosomal condition.

Down syndrome, trisomy 21, genetic disorder, intellectual disability, developmental delay, chromosomal abnormality, hypotonia, congenital heart disease, speech therapy, occupational therapy, early intervention, inclusive education, special needs, genetic counseling, physical therapy, facial features, prenatal screening, cognitive development, social inclusion, adaptive skills,

#DownSyndrome #Trisomy21 #GeneticDisorder #IntellectualDisability #DevelopmentalDelay #SpecialNeeds #InclusiveEducation #EarlyIntervention #SpeechTherapy #OccupationalTherapy #PhysicalTherapy #GeneticCounseling #SocialInclusion #CognitiveDevelopment #AdaptiveSkills #Hypotonia #CongenitalHeartDisease #PrenatalScreening #ChromosomalAbnormality #DownSyndromeAwareness

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Coding Mutations to Meningomyelocele

The contribution of de novo coding mutations to meningomyelocele

Meningomyelocele (also known as spina bifida) is considered to be a genetically complex disease resulting from a failure of the neural tube to close. Individuals with meningomyelocele display neuromotor disability and frequent hydrocephalus, requiring ventricular shunting.

A few genes have been proposed to contribute to disease susceptibility, but beyond that it remains unexplained. We postulated that de novo mutations under purifying selection contribute to the risk of developing meningomyelocele. Here we recruited a cohort of 851 meningomyelocele trios who required shunting at birth and 732 control trios, and found that de novo likely gene disruption or damaging missense mutations occurred in approximately 22.3% of subjects, with 28% of such variants estimated to contribute to disease risk.

The 187 genes with damaging de novo mutations collectively define networks including actin cytoskeleton and microtubule-based processes, Netrin-1 signalling and chromatin-modifying enzymes. Gene validation demonstrated partial or complete loss of function, impaired signalling and defective closure of the neural tube in Xenopus embryos. Our results indicate that de novo mutations make key contributions to meningomyelocele risk, and highlight critical pathways required for neural tube closure in human embryogenesis.

Mutations, Genetic Variability, DNA Alterations, Genomic Instability, Somatic Mutations, Germline Mutations, Point Mutation, Frameshift Mutation, Missense Mutation, Nonsense Mutation, Silent Mutation, Deletion Mutation, Insertion Mutation, Duplication Mutation, Chromosomal Aberrations, Single Nucleotide Polymorphism (SNP), Mutagenesis, Oncogenic Mutations, Hereditary Mutations, Evolutionary Adaptation

#Mutations #Genetics #DNAChanges #GenomicInstability #SomaticMutation #GermlineMutation #PointMutation #FrameshiftMutation #MissenseMutation #NonsenseMutation #SilentMutation #DeletionMutation #InsertionMutation #DuplicationMutation #ChromosomalMutation #SNP #Mutagenesis #OncogenicMutation #HereditaryMutation #Evolution

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Healthcare startups

Healthcare startups to see surge in M&A as funding dries up

Healthcare startups are set for increased mergers and acquisitions in 2025, driven by cash-strapped firms, declining revenue multiples, and investor caution, particularly in diagnostics and care delivery.

Healthcare startups are poised for increased mergers and acquisitions (M&A) in the current calendar year as revenue multiples decline and cash-strapped firms struggle in a tight funding market, according to early-stage healthcare-focused investment firm W Health Ventures.

The consolidation wave is expected to be most pronounced in diagnostics, where large pathology chains are likely to acquire smaller, hyperlocal labs and radiology centres to expand their geographic reach. Care delivery companies specialising in single fields such as IVF, eyecare, and oncology may also see exits, with promoters selling to private equity-backed platforms, said Namit Chugh, principal at W Health Ventures.

Investor caution has left many healthcare startups strapped for cash. Funding in the sector remained at nearly half of the average levels seen in 2021 and 2022, as backers waited for firms to achieve product-market fit before committing capital. As a result, 70% of early-stage healthcare startups have not raised a funding round since then, W Health Ventures said in a report on India’s healthcare ecosystem.

“A large number of healthcare startups with low cash reserves will become lucrative acquisition targets,” Chugh said. Late-stage, well-funded startups and global private equity firms are expected to drive most of the deal-making. With revenue multiples in private markets down by 60% from 2022 levels, acquisitions are now significantly more attractive for buyers.

Earlier this year, Wysa, an AI-powered mental health chatbot backed by W Health Ventures, merged with US-based April Health to integrate AI-driven mental health support into primary care, signaling a trend of strategic tie-ups.

Among different M&A models, acqui-hiring —where talent is acquired rather than just the business — could gain traction, offering startups an opportunity to expand service lines while securing high-quality, experienced teams. “We foresee more such transactions in 2025, including acquisitions via our portfolio companies,” W Health Ventures stated.

While consolidation accelerates in diagnostics and care delivery, quick-commerce healthcare ventures may struggle. Pharmacy quick-commerce startups face intensifying competition, which could lead to aggressive cash burn through speed and discount wars against local pharmacies. Inventory management challenges and regulatory compliance hurdles further compound the risks.

“By the end of 2025, we anticipate that at least a few q-commerce healthcare players will lose this race,” the report said. “The real question remains — aside from critical patients, does anyone really need medicines in ten minutes?”

Since 2021, W Health Ventures has been investing from its $100-million Fund I in startups such as BeatO, a personalised diabetes management platform; Mylo, a parenting community; AI-guided mental health firm Wysa; and Reveal Healthtech, which provides AI and engineering services to the healthcare industry. The firm is currently raising its second fund, targeting another $100 million.

Healthcare, medical research, patient care, public health, disease prevention, clinical trials, health technology, digital health, telemedicine, medical innovation, epidemiology, healthcare policy, mental health, precision medicine, biomedical science, health informatics, global health, personalized medicine, healthcare management, regenerative medicine,

#Healthcare #MedicalResearch #PatientCare #PublicHealth #DiseasePrevention #ClinicalTrials #HealthTech #DigitalHealth #Telemedicine #MedicalInnovation #Epidemiology #HealthcarePolicy #MentalHealth #PrecisionMedicine #BiomedicalScience #HealthInformatics #GlobalHealth #PersonalizedMedicine #HealthcareManagement #RegenerativeMedicine

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