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GDF15 Protein

Scientists engineer proteins that can now make obese mice to exponentially lose weight and lower their cholesterol. This is somewhat crucial now that almost 40% of Americans are now considered obese; can these findings create a pill for humans that can have the same effect? Scientists from a biotechnology company called Amgen Inc. have found a naturally occurring protein within both monkeys and rats that have brought about significant changes in obesity in both animals. These protein provided healthy weight loss and rapid improvements on measures of their metabolism and heart health.

In mice who received a bioengineered version of their GDF15 protein, researchers observed that these mice would opt out of the extra-rich condensed milk, that they normally go crazy about, for their standard mouse food. After 35 days, these mice who were bioengineered lost approximately 20% of their body weight, while the placebo mice gained 6% of their starting weight. Insulin levels and total cholesterol readings were distinctly improved in the treated animals as well.

Chromosome 19 (human)

This reengineering is suggested to have the power to decrease or turn off the urge of reward-driven eating that drive many people to becoming obese, or inhibiting others from losing weight. Foods such as doughnuts, milkshakes, or bacon cheeseburgers seemed less enticing. Some of the weight-loss medications approved by the FDA similar to this reengineering appeared to nudge food preferences of obese patients into healthier directions, further leading to better health conditions. The GDF15 protein fidgets with the chemical signaling systems of humans, so scientists have been working to find equal options with similar benefits that can work together to activate many different systems that work together to increase weight loss.  



http://www.latimes.com/science/sciencenow/la-sci-sn-weight-loss-protein-20171019-story.html

At the Institute for Equine Genomics at Bingham University researchers worked to better understand the genetics behind breeding success in horses. Gene variants are one component they look at to determine if a horse could be a great racehorse. Seabiscuit is a legendary racehorse that does not fit the typical characteristics of a great thoroughbred. He was small, “lazy”, and completely written off after losing his first 17 races. However, after beating Triple Crown winner War Admiral as an underdog, he was voted 1938 Horse of the Year. 

A few years ago, Jacqueline Cooper from the Seabiscuit Heritage Foundation got in touch with the Institute, asking if they could test a fifth-generation of Seabiscuit for breeding purposes as well as learning more about the ancestor’s genetics. Because the relationship was so distant, this wasn’t possible. Instead, they extracted a DNA sample from Seabiscuit’s silvered hooves. Removing and preserving a champion racehorse’s hooves was once customary. The owner kept them as keepsakes and decorative mementos.

seabiscuit silver hoof.jpg

Student Kate DeRosa and Andy Merriweather, director of the campus Ancient DNA and Forensic Laboratory, drilled into the coffin bone of the hooves. The coffin bone is the bottommost bone in a horse’s hoof. After extraction they found that the mitochondrial DNA was still intact. This DNA allowed the researchers to verify the maternal lineage and prove that the hooves did, in fact, belong to Seabiscuit. They also found that the nuclear DNA had been degraded due to its age and the chemical treatment it underwent while being silvered. Despite this, Kate was still able to sequence genes associated with optimal racing distance. They found that Seabiscuit had variants that are found in successful distance runners. Most interesting was that his genes also included minor variants found in good sprinting horses. This rare combination explains Seabiscuit’s record. He won races by both very short and extremely long distances. 



Kate DeRosa.jpg

seabiscuit hoof2.jpg

When looking at successful racehorses today that have a genotype similar to Seabiscuit’s, they tend to be late bloomers when compared to other genotypes. This is much like Seabiscuit’s career; he didn’t begin winning until he was 4. The Institute will continue sequencing Seabiscuit’s genes looking for links to physical attributes as well as temperament traits. They theorize that Seabiscuit could have had behavioral genes that filled him with such a desire to win that it overpowered his less than ideal physical traits. They are interested to see how his DNA differs from modern racehorses knowing how different thoroughbreds looked in the past. The researchers also mention that it is not currently possible to clone Seabiscuit due to the low quality of nuclear DNA.

Tammariello, Steven. “Scientists Extract DNA From Seabiscuit's Hooves To Figure Out How He Was So Fast.” Smithsonian.com, Smithsonian Institution, 29 Oct. 2018, www.smithsonianmag.com/history/scientists-extract-dna-from-seabiscuits-hooves-to-figure-out-how-he-was-so-fast-180970649/.


One man sent nine samples of his DNA to three different companies and he received six different results. Rafi Letzter, a writer from Live Science, sent his DNA to AncestryDNA, 23andMe and Nat Geo, which uses Helix to process the raw DNA while Nat Geo interprets the DNA. Letzter knows he comes from a family with strong Jewish ties but he has never taken a test before. 

AncestryDNA samples:

Three samples were sent, all under different names but only two got processed, as one resulted in an error preventing him from accessing his results. 

First sample:

Second sample:


23andMe Samples:

Letzter sent three samples to 23andMe. At first, two samples both reported low 90s (percent) in the Ashkenazi Jewish origin. The third sample was sent under a female name and was labelled as female, even though Letzter is a male. The sample was processed fine but 23andMe asked for more personal information since the sample came from someone with "unexpected chromosomes." However, while reporting on this story, 23andMe updated its DNA interpreting system, meaning it reassessed all of the DNA already in it system. After the update, the reports came back as 100 percent Ashenazi Jewish. 

Nat Geo and Helix:

Again, three DNA samples were sent to this company for testing, but only two were successful in retrieving results. 

First sample:

Second sample:

As you can see, this company found that Letzter was significantly less Ashkenazi Jewish than the previous two companies.


Why does this matter? And how does this happen?

Well, it kind of doesn't matter, and it happens for a number of reasons. The reason for population genetics is to focus more on where groups of people moved and when. Ancestry isn't an exact science since humans have never been exact/hyper-distinct groups of people. According to the article, "To divide people into groups, Platt told Live Science, researchers make decisions: For example, they'll say, the members of this group of people have all lived in Morocco for at least several generations, so we'll add their DNA to the reference libraries for Moroccans. And people who had one grandparent with that sort of DNA will hear that they're 25 percent Moroccan. But that boundary, Platt said, is fundamentally 'imaginary.' 'There is structure to history,' he said. 'Certain peoples are more closely related to each other than to other peoples. And [commercial DNA companies] are trying to create boundaries within those clusters. But those boundaries never really existed, and they aren't real things.'"

What could this mean for the future of commercial DNA testing companies?

This lack of certainty could cause a drop in consumer faith in the products. If you can send in nine different samples and get six different results, it'd be hard to be sure which report, if any, you should believe. Also, as we heard in class, 23andMe is now going to test how you respond to certain medications. Well, if their ancestry data is so subject to error, how can the reports on medication response be trusted? That's certainly something 23andMe can't afford to be wrong about. 



This article talks about a recent development that a team of scientists have recently uncovered. This development is that based on genetic markers the scientists have created a test to help predict the lifespan of humans. The test shows that some people are genetically predisposed to live 5-10 years longer than some of their counterparts. The test is based on 21 different genetic locations, and how they pertain to getting certain diseases such as Alzheimer's, or Lung cancer. Predisposition to these diseases is thought to be cause of much of the variation in the lifespan predictions. Interestingly, the student didn't find any information about other types of cancers, and is thought to be related to this specific time period(present). This idea came up because in the past even if a person was predisposed to get Lung cancer, there wasn't as great of a chance as there is today, due to the smoking epidemic. In the future, scientists hope to more precisely understand these genetic markers, and eventually try to slow down the aging process. 


https://www.medicalnewstoday.com/articles/323414.php

Sandoiu, Ana. “Scientists Create Genetic Score That Predicts Lifespan.” Medical News Today, MediLexicon International, 22 Oct. 2018, www.medicalnewstoday.com/articles/323414.php.


This article talks about how certain genes in our body are turned on/off due to how transcription factors bind to parts of the chromatin. A study shows that the key to different cancer types is found in binding patterns. This study will allow biologists to understand the nature of cancer. Scientists at Stanford University School of Medicine are completing this task and trying to understand the underlying connection between the two. Transcription occurs when information is taken from the cell and is encoded in the gene, and then rewrites in the form of the messenger RA. DNA is tightly wounded in the nucleus of a cell with a protein called Chromatin. Transcription occurs when it finds of section of chromatin and binds to it and then that region of DNA unzips which allows transcription to happen. In the presence of cancer, this process malfunctions. This results in a change in gene activation. 

According to Drug Target Review, "One finding showed that mutations can occur within the chromatin sequence, thereby creating a new and accessible site for a transcription factor to bind. Once the protein attaches to the site, a new gene is expressed, causing significant biological changes."


Even though the study is not in a clinical setting yet, researchers believe that this study will better cancer diagnosis and peoples susceptibility to cancer. 


https://www.drugtargetreview.com/news/36417/chromatin-dna-protein-binding-cancer/

New findings on malaria:

Scientists found out how the immune system defends against malaria by the antibodies working together that can create a certain protein that attaches to the back of the parasite and creates a corkscrew like wrap around the parasite. This blocks the parasite from starting its life cycle inside the human body and thus protecting against infection. "The first images were quite remarkable and gave us our first insights into how the extended surface peptide could be recognized," says Andrew Ward, PhD, a Scripps Research professor By being able to capture this we can now see the way the parasite reacts with the antibodies, and it could help scientists create a new vaccine.  

The study that founded this breakthrough is working to improve the current trial vaccine which is called RTS,S. The current trial vaccine has a 50% success rate depending on the vaccine regime. The reason why this is so important is because millions of people die each year due to malaria, the globe has committed to worldwide research to help fight this parasite.

Scripps Research Institute. "Scientists capture images of antibodies working together against malaria." ScienceDaily. ScienceDaily, 23 October 2018. https://www.sciencedaily.com/releases/2018/10/181023150011.htm

In this document it says that in the future during an annual physical that your doctor may test or look and your genome. Why would they do this? The reason for this would be that then the doctors would be able to treat a future disease before it even develops so then you wouldn't even have to overcome any of the symptoms, because they would already be treated.






However this may not be as useful as it sounds. According to this chart that was displayed on the website a very large portion of people that are doing these genome tests are of white European background. Since at this point in time there is not enough information of people of other backgrounds the researchers are unaware of how to treat complications for people of other ethnic backgrounds. Meaning that researchers are coming out with preventive medications or tests however they are saying that these tests are only eligible for people of this white European background.

While a large portion of all humans DNA is the same because we are all humans regardless if we are tall, short, red hair, blonde, or the color of our skin, however the differences among races is the pattern that their genes occur. Since Europeans originated in Europe and Africans originated in Africa it makes sense that our gene pool would be different due to the geographical barriers. With this different gene pool it causes people of different races to have different diseases or traits, such as sickle cell disease which is prevalent in African Americans.

With the difference in genomes it is ideal that if researchers would like to continue their study with this new type of research with genomes that is called precision medicine they need to get more people to test their genome that have different ethnic backgrounds. If they wanted to continue this I think that beginning at possibly next year when people come in for a physical they could test their DNA and then once they have enough data of all the patients that have come in they then would be able to begin this new research project.



https://www.vox.com/science-and-health/2018/10/22/17983568/dna-tests-precision-medicine-genetics-gwas-diversity-all-of-us

A machine learned how to identify antibiotic resistance genes in bacteria

Researchers at the University of California-San Diego recently trained a machine learning algorithm to identify and predict genes that drive antibiotic resistance in bacteria. The method was tested on Mycobacterium Tuberculosis, which causes TB. It identified 33 known resistance genes, but astonishingly found 24 new ones. Researchers have hopes that the method can be used to predict resistance in other infection causing bacteria and pathogens. "Knowing which genes are conferring to antibiotic resistance could change the way infectious diseases are treated in the future." Jonathan Monk was a co-author of the paper and works in Bio engineering in San Diego. He goes on to say that Physician's could one day use the algorithm to sequence the strain of a particular infection and figure out which antibiotics are going to be more effective in treating it. Looking at the specific genes can give medical practitioners a great advantage in treating difficult infections, including those that are on the CDC's ever growing list of bacterial strains to watch out for.

Other authors and researchers on the work have another thought that seems rather interesting. Bernhard Palsson, professor of Bio engineering at UC San Diego had this to say. "Through this machine learning analysis of the pan-genome -- the complete set of all the genes in all the strains of a bacterial species -- we can better understand the properties that make these strains different." If this turns out to be true, then this also can greatly impact how we handle antibiotic resistance for all kinds of different strains of bacteria. This research could potentially yield great results for the study of infectious disease.

When the flu season was booming last spring, a woman checked into a Huston hospital and was given a few tests. Her blood was drawn and sent to the hospital lab. Although, then her blood sample was sent to a startup called Karius that is located in Redwood City, California. At this company the woman's blood sample was analyzed to see what DNA fragments and other microbes that happened to be in her body at that time. This company was able to find a DNA strand that kept appearing over and over. This DNA strand contained rickettsia typhi. Rickettsia typhi is a type of bacteria that is usually found in the bowels of fleas and causes typhus in rats. This type of bacteria only lives in the warm environment of a living human or animal. At this time typhus was starting to make a return in Texas which is spread by the common flea. It turns out that  rickettsia typhi cannot be cultured so the hospital lab test would have not detected it. Since this woman's blood was sent to Karius it was found that she did not have the expected flu.

One of the reasons that hospitals are now starting to send blood samples to companies like Karius is to determine pathogens that are making patients sick. These DNA tests can even show results faster than the typical hospital lab test. For example, in the field of oncology, it has become normal to send in a sample of a tumor tissue for DNA testing. This type of testing allows for patients to get treatments aimed at their specific type of cancer.

There is still work to be done for this type of software that would be able to detect bacterias, fungi, diseases, or parasites just from DNA. If a doctor is wanting these types of results one would need to create an enormous database that could evolve very quickly. Not to mention, these types of tests are very expensive. Karius' tests costs around $2,000. Although, the more the costs drop, genetic databases get larger, which causes the research to be more accurate. It is a great approach for getting diagnoses more quickly. 

https://www.wired.com/story/dna-sequencing-detect-infectious-disease/

Cystic Fibrosis

Cystic fibrosis is a genetic disease that is caused by the genetic mutation that changes the protein that regulates the movement of salt in and out of cells.  the result of this is a sticky thick mucus in the respiratory, digestive, and reproductive systems, they also produce and increased amount of salt in their sweat. This disease is an inherited trait that is passed down the generations; the gene is recessive so both parents will have to have the gene for the child to have the mutation, if the child only has one of the genes it will become a carrier for the disease and their child could have the disease if their partner is also a carrier. The cystic fibrosis gene is mostly common in white people with a Northern European ancestry. This topic is interesting to me because this gene runs in my family; my cousin Hailey has cystic fibrosis. This 23andme test helped find out more about myself and my family. It also gives me and idea if i’m a carrier for this genetic mutation; this is why genetic testing is important to me. You can find out more about your history and the possibility to have or pass on a mutation of your genes.

Once the mother gets tested if her child will have the disease she can then go through genetic therapy and learn how she can help and prepare for the child’s condition. The genetic counselor will also help you and once the child is old enough to cope with the disease since is is terminal and most people don’t live past the age of 30-40 yrs of age. Most who have the disease go through rigorous treatments and daily medications along with a special diet. With the hope of genetics advancing the thought of one day being able to take the cystic fibrosis gene out and replace it with the healthy one is amazing.

Mayo Clinic Staff. “Cystic Fibrosis.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 13 Oct. 2016, www.mayoclinic.org/diseases-conditions/cystic-fibrosis/symptoms-causes/syc-20353700.

According to European College of Neuropsychopharmacology, a recent study shows that there is evidence of depression and trauma being linked to a shorter life span then that of a healthy person. Depression can cause a large amount of changes in the DNA of those who suffer greatly from it.

The study worked with 811 depressed patients along with 319 control subjects (Netherlands Study of Depression and Anxiety). The team extracted blood from each individual patient and studied it. The body process DNA by methylation, this is when CH3 is added to DNA. Methylation allows the gene function to be changed without changing the persons gene sequence. The team found that patients who suffered from MDD (major depressive disorder) showed an increased amount of DNA methylation, which explains a biologically increased age. On average, the patients were 8 months to 1 year older than that of the healthy patients. In rare cases, people who suffer with extreme depression can be biologically 10-15 years older. To confirm their results, the team analyzed "post-mortem" brain samples. They found similar results in both the blood sample and the brain tissue. Patients were asked questions about their trauma. The trauma included; emotional neglect and sexual/physical abuse all before the age of 16.

A quote from the article states, "When we look within the group of depressed individuals, we see that childhood traumas experienced before the age of 16 were associated with even more pronounced epigenetic aging later in life. Of course, these are associations, so we need long-term linked studies (longitudinal studies) to be able to draw any conclusions whether the trauma causes the epigenetic aging."

This is interesting because it shows the serious effect that childhood trauma has on your biological aging and how it can possibly speed up your "epigenetic" clock. 


ScienceDaily. (2018). Study shows DNA of people with childhood abuse or depression ages faster. [online] Available at: https://www.sciencedaily.com/releases/2018/10/181009113620.htm [Accessed 10 Oct. 2018].

In an article by Science Daily, a study of 811 patients with depression and 319 control subjects from the Netherlands Study of Depression and Anxiety showed evidence that the DNA of those who suffered trauma such as violence, neglect or sexual abuse exhibit a biological age older than their calendar age. The DNA displayed an average of an 8-month increase in age. In some cases of extreme depression, patients were found to have a biological age of 10 to 15 years older than the chronological age. Evidence of this aging phenomenon was found in post-mortem brain tissue and blood samples (this study used specifically blood samples to provide their data). In groups of depressed individuals, patients who suffered from their trauma before the age of 16 exhibited with more pronounced aging later in life. This study seemed to prove the existence of something called an "epigenetic clock" which shows modifications of DNA as an indicator of biological age. 

Summary of the article: DNA from people who suffer from major depression is biologically older than that of healthy people by on average 8 months, suggesting that they are biologically older than their corresponding calendar age. This effect was greater in people who have had childhood trauma, such as violence, neglect or sexual abuse, who show a biological age around a year older than their actual age.

Recently, gene therapy has emerged as one of the leading methods of genetic engineering. When scientists first proposed gene therapy, a majority of society generally disagreed with the idea; over time, society has slowly started to accept gene therapy as an ethical procedure. According to an article published by The Scientist on August 16, 2018, directors of the National Institutes of Health (NIH) and the US Food and Drug Administration (FDA) have discussed "limiting the role of the NIH in assessing proposals for gene therapy experiments" (Grens 2018). In other words, scientists can conduct gene therapy experiments with lighter regulations. Additionally, the NIH will limit their time evaluating gene therapy experiments when they are administered by scientists. 

Simply, gene therapy allows scientists to "[r]eplace a mutated gene that causes disease with a healthy copy of the gene" ("What Is Gene Therapy?", 2018). Through this technique, researchers and doctors can likely treat different diseases caused by genetics; gene therapy could potentially cure some of these genetic diseases! Despite the possibilities, gene therapy requires more research and information before it becomes widely accepted by society. Many years may pass until gene therapy becomes a standard practice; for now, it could be scientists' best approach to curing cancer and other genetic-based diseases!

Unfortunately, gene therapy is not completely foolproof; as Collins and Gottlieb state, "...there is no longer sufficient evidence to claim that the risks of gene therapy are entirely unique and unpredictable—or that the field still requires special oversight that falls outside [the] existing framework for ensuring safety" (Grens 2018). Luckily, scientists can more freely apply this specific procedure without strict regulations. Scientists can also spend more time researching different biotechnological methods instead of focusing only on gene therapy. Regulations on gene therapy still remain stern, but scientists are now allowed more leeway on their research. A vast majority of individuals still disapprove of the lighter regulations regarding gene therapy (see article), but gene therapy–and possibly other biotechnological research methods in the future–could be a huge breakthrough in the scientific community!

~~~

Grens, Kerry. “The NIH Loosens Grip on Gene Therapy Trials.” The Scientist, 16 Aug. 2018, www.the-scientist.com/news-opinion/the-nih-loosens-grip-on-gene-therapy-trials-64652

“What Is Gene Therapy? - Genetics Home Reference - NIH.” U.S. National Library of Medicine, National Institutes of Health, 2 Oct. 2018, ghr.nlm.nih.gov/primer/therapy/genetherapy.

Luigi Cavalli-Sforza

On August 31, 2018, age 96,the beloved geneticist Luigi Cavalli-Sforza passed away.  If you're wondering why this is important to genotyping, it is extremely.  Cavalli-Sforza paved the way for the science of genotyping.  Although he would have called it genetic geography!  He started off with blood samples and church records to study ancestry of those willing.  He built the study of genetic geography from archaeology, linguistics, anthropology, statistics and of course genetics.  Luigi was the first to be able to explain how we are all able to be linked back to African descent and how we spread out throughout the globe.  "Dr. Cavalii-Sforza was the first scientist to predict that there is  “enough information in genes to determine where people came from in the world and who they’re most closely related to”."  There were many people that doubted him in his early times of research, but he kept moving.

Luigi Cavalli-Sforza was a man who would not give up.  After his years of being a professor and retiring, he continued to do research.  He kept building his research to go further and further back in ancestors.  In fact, he was able to trace DNA back 100,000 years ago.  He discovered this DNA led back to Africa.  As his research continued, he won a Nobel Peace Prize and much praise.  In 1990, he wanted to start the Human Genome Diversity Project.  This was where he would collect DNA in hair, blood, and saliva from all cultures.  He was put under extreme heat for this project being as it was seen to be racist.  The project went on despite the criticism.  The results are still a resource today.  It is easy to say Dr. Cavalli-Sforza will be missed.

 

Image result for luigi cavalli sforza           Image result for luigi cavalli sforza



Grady, Denise. “Luigi Cavalli-Sforza, 96, Who Tracked Genes Through History, Dies.” The New York Times, The New York Times, 19 Sept. 2018, www.nytimes.com/2018/09/19/obituaries/luigi-cavalli-sforza-dies.html.


Mosquitoes and Genes

Writers of The Scientist–a factual science magazine–recently published an article which discusses how gene drives can wipe out certain kinds of mosquitoes and prevent future cases of malaria outbreaks. Gene drives are defined as "a genetic element that insures its own inheritance"; simply, researchers can insert gene drives into an organism and cause it to reproduce with the edited gene (Yeager 2018). Through gene drives, researchers Tony Nolan and Andrea Crisanti hoped they could prevent female mosquitoes from reproducing offspring (see original article). In their original study, the gene drive experiment was tested on female laboratory mosquitoes beginning in January 2017.

Almost two years later, the two scientists reported successful results of the gene drive experiment! As Yeager states, "After eight generations, the drive had spread through the entire [mosquito] population, such that no eggs were laid [by the females]" (2018). Although the experiment proved successful in the laboratory, situations in the wild could cause mosquitoes to become resistant to the gene drive; some mosquitoes may even develop a mutation where the gene drive no longer effects the mosquito population. Crisanti also explicitly states, "[i]t will be at least 5-10 before we consider testing any mosquitoes with gene drive in the wild" (2018).

The original article provides a much more in-depth analysis on the thought process behind gene drives, but there is no denying the potential behind gene drive technology. This technology and recent discovery is a huge breakthrough in the genetics community; through more research and time, scientists could potentially control other harmful diseases similar to malaria. Nolan and Crisanti's research is brilliant; gene drives hold great promise for the future!


Recent/follow-up article: Yeager, Ashley. “Study: Gene Drive Wipes Out Lab Mosquitoes.” The Scientist, 24 Sept. 2018, www.the-scientist.com/news-opinion/study--gene-drive-wipes-out-lab-mosquitoes-64849

Original article: Nolan, Tony, and Andrea Crisanti. “Using Gene Drives to Limit the Spread of Malaria.” The Scientist, 1 Jan. 2017, www.the-scientist.com/features/using-gene-drives-to-limit-the-spread-of-malaria-32286

Click here to view the entire gene drive thought process through infographics!