BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: genetic mutation

CRISPR Injections: The Fix for Genetic Mutations?

A recent study shows the first success of CRISPR being directly injected into the bloodstream, reducing the effects of a toxic protein, caused by a genetic mutation, for up to 1 year. CRISPR-Cas9 is a fairly new genetic technology that allows scientists to edit and manipulate specific DNA sequences; it can remove, add, or alter specific sections of DNA. There are two key components that are involved in the CRISPR-Cas9 technology. Cas-9, an enzyme, works to untwist and unzip the DNA at a specific location. This Cas-9 enzyme is very similar to the helicase enzyme. As we learned in AP Biology, helicase untwists and unzips the DNA. However, unlike the Cas-9 enzyme, helicase unzips the whole DNA strand as the DNA is preparing to replicate. The second key component to CRISPR is guide RNA or gRNA. Guide RNA works to guide the Cas-9 enzyme to make sure it cuts the right part of the DNA. 

CRISPR-Cas9 mode of action

A condition called transthyretin (TTR) amyloidosis, inherited from a gene mutation, causes numbness, nerve pain, and heart failure in adults. These symptoms are caused by a buildup of nerves and organs of misfolded TTR proteins, which are made by the liver. Intellia Therapeutics and Regeneron Pharmaceuticals funded research in which scientists figured out a way to fix the genetic mutation. They created a fat particle that contained messenger RNA that codes for Cas-9, CRISPR’s cutting enzyme. This fat particle was then injected into the subjects. Once injected, the gRNA guides the Cas-9 enzyme to cut out the mutated TTR genetic code from the DNA in liver cells. Once this code is cut out, the cells repair the DNA code to a non mutated form; this stops the production of the TTR protein. 

One month after six patients received this injection, these companies reported that the levels of TTR in the patients blood fell drastically. While the symptoms of these patients have not improved, the blood levels gave enough evidence to prove that the injections of CRISPR-Cas9 were successful. In addition, this form of treatment has led to no safety issues. These companies and many others are continuing to test this technology with TTR patients as well as patients with other genetic mutations. 

 

Redesigned Cas9 protein provides safer gene editing than ever before!

Gene editing is a group of technologies that give scientists the ability to change an organism’s DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed. A recent one is known as CRISPR-Cas9, which is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.

One of the challenges that come using CRISPR-based gene editing within humans is that the molecular machinery may sometimes make edits to the wrong section of a host’s genome. This is problematic because it creates the possibility that an attempt to repair a genetic mutation in one location in the genome could accidentally create a dangerous new mutation in another spot. Scientists at The University of Texas at Austin have redesigned a key component of a widely used CRISPR-based gene-editing tool, called Cas9, to be thousands of times less likely to target the wrong stretch of DNA while remaining just as efficient as the original version, making it potentially much safer.

The CRISPR-Cas9 system works similarly in the lab. Researchers create a small piece of RNA with a short ‘guide’ sequence that binds to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. As in bacteria, the modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location. Although Cas9 is the enzyme that is used most often, other enzymes can also be used. Once the DNA is cut, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.

Other labs have redesigned Cas9 to reduce off-target interactions, but so far, all these versions improve accuracy by sacrificing speed. SuperFi-Cas9, as this new version has been named, is 4,000 times less likely to cut off-target sites but just as fast as naturally occurring Cas9. Scientists say you can think of the different lab-generated versions of Cas9 as different models of self-driving cars. Most models are really safe, but they have a top speed of 10 miles per hour.

In my opinion, setting aside any and all ethical concerns, genome editing is of great interest in the prevention and treatment of human diseases. Currently, most research on genome editing is done to understand diseases using cells and animal models. Scientists are still working to determine whether this approach is safe and effective for use in people. It is being explored in research on a wide variety of diseases, including single-gene disorders such as cystic fibrosis, hemophilia, and sickle cell disease. It also holds promise for the treatment and prevention of more complex diseases, such as cancer, heart disease, mental illness, and human immunodeficiency virus (HIV) infection.

CRISPR to the Rescue

If you are reading this right now, it means you are not blind. Aren’t you so fortunate to have healthy vision? Others aren’t as lucky. The genetic disorder of blindness is something that effects many people.  However, what if I told you that there may be a way to prevent the passing of a genetic mutation such as blindness? It’s called CRISPR.

Before I get into how CRISPR can help prevent blindness, must know what CRISPR is. CRISPR, short for CRISPR-Cas9, is a tool used for editing genes of organisms by modifying the DNA. By changing the DNA sequence, this causes for a change in gene function. Essentially, CRISPR acts as a scissor that is able to cut and edit the DNA sequence.

The way genes are manipulated is by having the components of one CRISPR sent over to another CRISPR, which then alters the structure of the sequence manually, and is called “gene editing”. This phenomenon was discovered only in 2017 when a University in Japan was able to capture and reveal to the world the exact process of this gene editing. Genes are compromised of chemical bases that bind together to form a sequence and every sequence creates something different. For example the sequence GATC when genetically edited with CRISPR can turn into CATG by just switching the C and G. This may seem small but can have a much larger effect on the organism.

This method can directly be used to alter the genetic mutation that causes blindness in a person by finding the spot in the genetic code in that is the root of the mutation and editing it to become normal. Another new way that CRISPR gene editing can be used is to combat sickle cell disease. This disease that causes the creation of mutated hemoglobin resulting in blood clots can also be fixed. Sickle cell disease effects 100,000 people in the US, and can only currently be treated with bone marrow transplants, but this can lead to other health issues according to Dr. Markus Mapara who studies CRISPR. DNA orbit animated

Through CRISPR, as found by Dr. Dounda and Dr. Charpentier, they can direct the Cas9 protein part of CRISPR, through a programable RNA, to locate specific areas of genetic code, in particular ones that are the root of a mutation that causes health issues such as Sickle cell disease. As we mentioned before, the CRISPR can then remove and replace the specific area with one that doesn’t result in the genetic mutation.

While there may be other treatments for these diseases, CRISPR is certainly the safer, healthier, and more effective way to combat them. They also haven’t had too much research on it yet, so we are only getting more and more information as time goes on. I personally don’t have any genetic mutations that I know of, but I know many people who do and who this could help. Hopefully we will be able to master the technique and put an end to genetic mutations!

 

How a Genetic Mutation Makes Rabbits do Handstands Rather than Hopping

Erin Garcia de Jesús in sciencenews explains on a genetic level why the domesticated rabbit, Sauteur d’Alfort, does a handstandRabbits of Okunoshima, August 2018 (03) to move quickly rather than hopping. The cause of this change in their behavior is due to a defective gene likely linked to their limb movement.

Scientists completed a study not only to understand the rabbit’s handstands but Leif Andersson claims it would contribute “to our basic knowledge about… how we are able to move”. To find out where the mutation occurred, scientists crossed Sauteur d’Alfort rabbits that do handstands with New Zealand female rabbits that hop. They scanned the genetic blueprints of their offspring and looked for mutations that didn’t appear in the offspring. They found a mutation in the RORB gene and concluded that it was a likely explanation for the rabbit’s handstands. In rabbits that have the mutation, there is much less RORB than in rabbits that don’t, this is because the “change creates faulty versions of the genetic instructions that cells use to make proteins”. A lack of RORB protein in interneurons, the spinal cord nerve cells, will cause the rabbits to lack the ability to coordinate their hind limbs. They are still able to walk normally when they are moving slowly by alternating their front and hind legs normally. Since hopping requires the synchronization of the hind legs the mutation prevents them from doing so, so “all rabbits with a RORB mutation use their front paws to move quickly,” Carneiro says. Though they were able to understand how the mutation in one gene affects the rabbit’s movements, the gene could potentially be affecting the rest of the rabbit too, but they are unsure. If the scientists could understand how the genetic defect affects the body on a more broad scaleGregor Mendel 2 then they could understand the way that all animals move. Though the rabbits may not ever be able to hop, these findings can help researchers to develop ways to repair human bodies when there are defects in the RORB protein that could potentially cause disease. 

In AP Biology this year, we learned about Mendel’s laws of inheritance and all about genetics. He studied how genes are passed down from the parent generation, recessively or dominantly. Mendel stated that a mutation in a single gene can cause a disease that will be inherited. In connection to the rabbit’s genetic mutation, a lack of the RORB protein causes the rabbits to have insufficient limb control, but the presence of the protein makes the rabbits ‘normal’. 

Comment below if you have ever heard of a genetic mutation that caused an animal to move in an abnormal way, I’d love to hear. I did some research and these Sauteur d’Alfort rabbits are incredibly rare and originate from France. Ironically enough, in French, their name means Alfort’s Jumpers! I also found a video of one of them if you want to watch it… click this link.

New research exposes and demonstrates how damaged cells survive the cell cycle

In recent news, the Center for Cancer Research have recently discovered a previously unknown phenomenon, which allows certain cells to continue through the cell cycle despite experiencing DNA damage. This also includes past natural safety checkpoints within the cell cycle that are designed to stop the problem from occurring. On January 13, 2021 researchers, in Science Advances, suggested that the timing of DNA damage was crucial for determining whether a faulty cell would survive the cycle.

When cells begin to divide and replicate as part of their natural cycle, they transition from their resting state to one called the G1 phase. In this phase, cells have several important checkpoint mechanisms to ensure that the cell is healthy enough to proceed onto the next stage of the cell cycle. If/when these mechanisms fail due to genetic mutations, cells can progress through the G1 phase unobstructed, which can ultimately lead to cancer.

It was previously believed that cells with DNA damage could not pass through these safety checkpoints in the G1 phase and that the cells would either repair the DNA damage or die. However, scientists helped uncover evidence proving that cells with damaged DNA can actually progress past these critical checkpoints. A team of scientists studied individual cells for days at a time, using live cell time-lapse microscopy, single-cell tracking software, and fluorescent biosensors to detect the cell’s safety checkpoint mechanisms. They added a substance to induce DNA damage for cells of different ages in the cell cycle. Strikingly, the majority of cells seemed to ignore the DNA damage because they failed to trigger the checkpoint between G1 and the next phase, and proceeded into the next phase anyway.

Further investigation revealed that the timing of DNA damage during the cell cycle influenced the likelihood that damaged cells would slip past the checkpoints. The researchers found that the cell’s response to DNA damage is relatively slow compared to the speed of the cell cycle. This means if cells were already very close to the next phase of the cell cycle at the time DNA damage happened, they were more likely to continue into that phase. If the cells were still early in the G1 phase, they were more likely to revert back to a resting state. These observations are a form of inertia, where the cell will continue moving towards the next phase regardless of safety checkpoint signals.

It was also discovered that cells which were genetically identical were more likely to share the same cell cycle fate than non-identical cells. This suggests that factors specific to the cells themselves influence their fate during the cycle, rather than random chance. More studies are needed to understand how these findings apply to cancer. Testing is also extremely important in order to fully understand what the long-term consequences of the checkpoint failures are and find out if the cells that entered the next phase despite considerable DNA damage can become cancerous and eventually form a tumor, which, in my opinion and most likely the opinion of others, will be groundbreaking for cancer research.

A Gene Mutation that Keeps You Awake and Functioning for Longer

INTRODUCTION:

Could a gene mutation really allow someone to finish college in two and a half years? The answer is yes! We all wish we could get by a function perfectly, or even better than normal, on less sleep. This is a reality for some, specifically people with a rare gene mutation. I saw an article titled, “Why Do Some People Need Less Sleep? It’s in their DNA,” and I thought this was a rather interesting topic, because I have never heard of less sleep ever being a positive thing. I am interested to see more research on this, and the possibility of it being an added benefit for others. It prompted me to think about whether or not this is something I would want, considering some of the implications. 

People with this gene mutation can get significantly less sleep than recommended for function, as little as three to four hours—without suffering any health consequences and while actually performing on memory tests as well as, or better than, most people. There is now a new study correlating to a new genetic mutation found with these “powers,” after previous studies revealed other types of mutations that may impact sleep.

 

HOW DID IT START?: 

To understand this rare ability when presented to them, scientist Ying-Hui Fu and her team, at the University of California, San Francisco, in 2009, began this study on some individuals, but also on mice, to simulate a similar sleep equilibrium to humans. After a woman came in claiming she was functioning at a high level on very short sleep time, scientists needed to understand, as lack sleep is typically correlates with health issues such as risk of heart attack, cancer, or even Alzheimer’s. They initially found a small mutation in the DEC2 gene, a transcriptional repressor (hDEC2-P385R) that is associated with a human short sleep phenotype. According to UCSF, DEC2 helps regulate “circadian rhythms, the natural biological clock that dictates when hormones are released and influences behaviors such as eating and sleeping. This gene oscillates this particular c schedule: rising during the day, but falling at night.” The newer study reveals that the DEC2 gene lowers your level of alertness in the evening by binding to and blocking MyoD1, a gene that turns on orexin production, a hormone involved in maintaining wakefulness. Fu says the mutation seen in human short sleepers weakens DEC2’s ability to put the breaks on MyoD1, leading to more orexin production and causing the short sleepers to stay awake longer.

THE NEW GENE MUTATION: 

In a new study, released on October 16, 2019, by Science Translational Medicine brought on by a mother and daughter duo, mice were studied again to mimic the human sleep pattern. The mice again required less sleep, and were able to remember better. In the study, researchers identified a point mutation in the neuropeptide S receptor 1 (NPSR1) gene responsible for the short sleep phenotype. The mutation increased receptor sensitivity to the exterior ligand, and mice with the mutation displayed increased mobility time and reduced sleep duration. Even more interestingly, the animals were resistant to cognitive impairment induced by sleep deprivation. The results and findings in the study point to NPSR1 playing a major role in sleep-related memory consolidation. NSPR1 is a gene that codes for a brain receptor that controls functions in sleep behaviour and awakeness. In the new study, when mice were given this gene mutation, there were no obvious health, wellness, or memory issues over time. Although the family members did not appear to experience any of the negative effects of sleep deprivation, the researchers make sure to emphasize that longer term studies would be needed to confirm these findings.

WHAT DOES THE FUTURE HOLD?: 

In the future, a possible drug could be produced to synthesize a change in one of these genes, as a possible treatment for insomnia or other sleep disorders. We would need a lot more research about their functions, though, because of possible negative neurological side effects. 

If a medication with these powers were to exist, do you think it would cause social issues regarding some  possibly forcing certain individuals to take it to work longer hours/get more done? Do you think that it should be available to everyone, or only people with certain conditions? Comment about this below. 

 

Could There be Good Gene Mutations?

Is there an epic battle occurring within our bodies right now? The classic battle royale between good and bad? I suppose in the body’s case the fight between good and bad genes.  There is a new field in medical research in which researchers are on the quest to find good gene mutations that fight against the disease causing mutations.  One individual, Doug Whitney, sparked the interest of a few doctors because he has fought his genetic odds to be health at 65 years old.  Whitney has a gene mutation, presenilin, that causes early onset Alzheimer’s disease in those who has inherited it. Whitney’s mother and 9 out of his 13 siblings were killed by this mutation and so Whitney’s fate seemed to be sealed.  However when Whitney reached his 40s and 50s having no symptoms he assumed he did not have the gene.  At 62 years old, Whitney, decided he would get a gene test.  He did have the gene.  This was an anomaly, He was doomed to have early onset Alzheimer’s Disease but had absolutely no symptoms. Although Whitney still have changes of getting Alzhiemers but the effects of his bad gene have been greatly delayed by another gene in Whitney’s DNA.  Whitney joined a study at Washington University in St. Louis led by Doctor Randall Bateman which recruited people with the early onset Alzheimer’s disease gene. This attracted the attention of Doctor Eric E. Schadt and Doctor Stephen H. Friend.  Doctor Schadt said that searching for good genes that protect against bad gene mutations is completely turning genetic research on its head.  Researchers have found gene mutations that partially protect diseases like osteoporosis, Type 2 diabetes, heart disease, and Alzheimer’s.  These good gene mutation’s partial protect have help to develop drugs to help fight certain diseases. Finding good gene mutations are substantially more difficult to find than bad genes, but the search has gotten a little easier with fast and inexpensive methods of sequencing DNA. Doctor Schadt and Doctor Friend decided to start the Resilience Project and search for good gene mutations that counteract bad gene mutations to help develop new break though treatments and drugs. They have contacted the researchers at Washington University, the research that Whitney is currently participating in.

For more information:

Article from NYT

Prokaryotic positive genetic influences

Genetics used for intrusion protection

About genetic testing

 

Hearing Loss Clue Uncovered

In the United States, approximately forty-eight million (twenty percent) of men and women suffer some degree of hearing loss, as it is the third most common physical condition after arthritis and heart disease. While it is most often associated with the population sixty-five and
older, hearing loss effects all ages, as thirty school children per out one-thousand are afflicted in some varying degree. An individual is able to hear sound involving the ear’s main structures. In age-related hearing loss, one or more of these structures is damaged: the external ear canal, the middle ear, and the inner ear. External ear canal impairment is related exclusively to conducive hearing loss. The middle ear, which is separated from the ear canal by the eardrum may be caused by sensorineural hearing loss. Lastly, the inner ear, which contains the cochlea, the main sensory organ of hearing. When the vibrations from the middle ear enter the cochlea it causes the fluid to move and the sensory hair cells pick up this movement. In response to the movement of the fluid the hair cells send an electrical signal up the auditory nerve to the brain where it’s recognized as sound.

 

Now, how do these different internal departments of the human ear gradually induce hearing loss? While we get older, some may develop presbycusis, which causes the tiny hair-like cells in the cochlea to deteriorate over time. Clarity of sound decreases, as the hairs are unable to vibrate as effectively in response to sound. Recently, otolaryngologists have discovered new evidence that human hearing loss relates to a certain genetic mutations. A study at the University of Melbourne revealed “a novel genetic mutation was first identified in 2010 as causing hearing loss in humans… now discovered that this mutation induces malfunction of an inhibitor of an enzyme commonly found in our body that destroys proteins – known scientifically as SERPINB6. Individuals who lacked both copies of this “good gene” were shown to have lost their hearing by twenty years of age.

 

Although this discovery is changing the way scientists previously viewed hearing loss, the answer to why this mutation, SERPINB6, is a catalysts for such loss, is inconclusive. However, this mutative gene has created a revelation for many: it is now not unusual to show gradual signs of hearing loss under the age of sixty years.

 

To better understand the effects of the mutant gene, mice were used in order to imitate the condition from youth to adulthood. At only three weeks of age, mice with SERPINB6 had begun to lose hearing – three weeks is equivalent to pubescent or teenage years in humans. And as we could have predicted, the mice continued to show a decrease in hearing ability, much the same as humans. Researchers examined the mice’s inner ear, which revealed the cells responsible for interpreting sound (sensory hair cells) had died.

 

Fortunately, this new discovery of a mutant gene in human sensory cells has created new attention to better understand the case of those who are effected by the condition. 

 

 

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