Monday, October 31, 2011

Fragile X and mRNA Editing

The article I found describes some new research into Fragile X Syndrome. Fragile X Syndrome is the most common form of heritable cognitive impairment (mental retardation) in boys and results from an expanding tripling repeat mutation on the FMR1 gene. People generally have 30 repeats of the sequence CCG in the fragile X area (long tip of the X chromosome), but people with Fragile X Syndrome have from 200-2,000 CCG repeats in that area. The FMR1 gene encodes the fragile X mental retardation protein (FMRP), which binds to and disables sites critical for brain neuron function when it is dysfunctional. Losing FMR1 completely is the most common cause of autism. Those with Fragile X Syndrome tend to have long faces and protruding ears and are affected by mental retardation, learning disabilities, and social anxiety.

University of Pennsylvania and Brown researchers have discovered that the FMRP protein is critical in mRNA-editing and the neuromuscular junction synapse. mRNA editing is the splicing of introns after transcription and NMJ is the basically the neuron function that stimulates muscles to contract (there’s a great interactive site that explains NMJ here: Mutations in FRMP seem to be connected to overgrowth in the NMJ synapse, which causes problems with nerve function. They studied fruit flies (Drosophila), which have a similar gene (dFRM1) which, when mutated, causes analogous issues to mutated FRM1. Two proteins are necessary for correct NMJ growth—FMRP and ADAR. ADAR affects mRNA editing and is itself directly affected by FMRP. When these proteins are dysfunctional, mRNA editing is damaged, which affects the NMJ synapse and causes the symptoms of Fragile X Syndrome.

This is interesting because, as Prof. Reenan of Brown writes, mRNA editing mistakes have been “implicated in epilepsy, suicidal depression, schizophrenia, and even some neurological cancers. These data are surely pointing in the direction of deep connections between numerous distinct diseases of the brain.” Perhaps mRNA editing flaws are an undercurrent of diseases of the brain.

Main Article:

Works Cited:

Human Genetics, 9 ed. Ricki Lewis

Sunday, October 30, 2011

Genetically modified mosquitoes eliminate dengue fever

Trials conducted by British start-up Oxitec, Ltd showed that genetically modified mosquitoes could eradicate dengue fever. The scientific team inserted two genes into the Aedes aegypt mosquito, a sterility gene, which prevents male mosquitoes' offspring from growing past the larva stage, and a fluorescent tag gene, which allows researchers to easily identify larvae that have inherited the sterility gene. Sterility is achieved by employing tetracycline-controlled transcriptional activation (tTa). The tTa gene produces a protein that then acts as a transcription factor for the tTa gene, triggering further production of the protein in a positive-feedback cycle, which forces the cell's resources away from synthesizing other proteins, eventually leading to the cell's death. The antibiotic tetracycline stops the positive-feedback cycle. Mosquitoes raised in the laboratory are exposed to tetracycline, so they can survive to adulthood and then mate with female mosquitoes when released in the wild. By mating with females that would have ordinarily mated with normal males, the genetically modified mosquitoes reduce the percentage of viable offspring, thus decreasing the population of the next generation of mosquitoes.

The first trial, which was conducted in 2009, introduced the modified mosquitoes equivalent to 16% of the population in the Grand Cayman study area, and the fluorescent marker was found in 10% of the larvae, demonstrating that the mosquitoes were effective sexual competitors, although not quite as competitive of their normal counterparts. A second as-yet-unpublished trial in 2010 saw an 80% reduction of mosquito population in the target area on Grand Cayman island. These trials show much promise compared to previous methods such as using radiation to sterilize the mosquitoes, which reduced the mosquitoes ability to compete with wild males. One issue that needs to be dealt with is keeping any females from being released; unlike males, females bite humans, and the effects of a genetically engineered mosquito's bite on humans is unknown. Future trials will hopefully show promise of genetically modified insects to eliminate all insect-borne diseases, including dengue fever and malaria.

Deadly Parasite juggles the number of its Chromosomes

Scientists have discovered a medicine-resistant parasite that has a copy number of chromosome that varies among individuals. While chromosomes almost always occur in pairs, the Leishmania parasite can reportedly have up to five copies of certain chromosomes. The "chromosome juggling" Leishmania parasite is transmitted by mosquito bites, and causes a disease called leishmaniasis, which accounts for 50,000 annual deaths worldwide.
Researchers gained in interest in the Leishmania parasite when they discovered that genetically similar specimens of the parasite responded very differently to the same medicine. Using next generation sequencing, researchers genotyped the entire genome of seventeen different strands of the Leishmania parasite. They hoped that they would find SNPs that explained the way that the parasite reacted differently to the same medicine. Instead, the researchers discovered that all of the Leishmania parasite strains had a different, unnatural number of chromosomes. It is believed that the "chromosome juggling" is a method the parasite uses to fight drugs and the human immune system. The Leishmania parasite is the only known organism to behave in this manner.

The original article can be found here.

Multiple studies of human brain function were conducted recently, which scientists hope will lead to new information about mental illnesses. Data was collected through studying gene regulation in donated brains from all ages (ranging from a few weeks after conception to old age). Gene regulation is where, how, and for how long each gene is turned on and off over the course of a person’s life. The team also divided up the brain into different regions of tissues so that it was possible to pinpoint the genes’ behavior to different locations of the brain. It was observed that the highest level of gene regulation change, when genes were producing the largest amounts of mRNA, occurred during the prenatal period and the second largest period was during the later period of the 50s to 70s. Although this research is not complete, looking at gene regulation as opposed to the actual gene content will illustrate larger variations between people and species and hopefully provide more explanations for mental illnesses.

Thirty-two teeth of the dinosaur species Camarasaurus, a common sauropod found in North America, were examined leading to new data about its life. The teeth provided evidence that these sauropods migrated from their normal habitats the flood plains during the dry seasons in search of food. These migration patterns are incredibly relevant because they could potentially be one of the evolutionary explanations for why the sauropods reached such large sizes. It is possible that something referred to as a feedback process occurred: the larger sauropods became, the easier it would be for them to migrate and get more food, and the more food they got due to migration, the larger they grew, therefore leading to an overall growth in size of the species. Through measuring the oxygen isotopes found within the various enamels of the fossilized teeth, scientists are trying to put together the sauropod migration patterns, which will hopefully provide even more information about their evolution.

A study was conducted at the University of Colorado that investigated the change in bodily functions that occurs as a Python is eating. When a python eats, its hearts and other organs grow in size due to hypertrophy. Hypertrophy is the enlargement of cells, which causes the overall enlargement of an organ. In humans, hypertrophy is often seen in the heart either in well-conditioned athletes when exercising or when someone has a heart attack/heart failure. Therefore by studying hypertrophy in Pythons, the scientists hope to be able to help prevent heart problems. The scientists figured out that only a combination of three specific lipids (fatty acids) were able to create hypertrophy in a Python; they were able to figure out this data by injected blood from a fed Python into a starving Python. The next goal was to figure out why this large increase in the amount of lipids did not have a detrimental effect for the Python’s help. The answer to this was that there was an enzyme, SOD (superoxide dismutase) that acted as an antioxidant that defended the cells exposed to oxygen. The scientists are optimistic that this new information will lead to preventions of heart attack and heart failure.

Thursday, October 27, 2011

BRCA1 Further Elucidated

I just saw this article about the BRCA1 gene and the recent progress made in understanding this gene as it relates to breast cancer.  We have talked a bit about this already, but this article discusses another discovery made just yesterday about it.

Genetic Basis of Human Metabolic Individuality

What if you could have medical treatment tailored directly to your metabolic circumstances. Research is showing more and more, that metabolism affects many genetic disorders. There is even a new technology, metabolomics, which measures how metabolism correlates to risk for disease and type of disease. In a test of 600,000 SNPs, "fifteen SNPs had previously been associated with metabolism-related conditions such as cardiovascular disease, kidney disease, gout, diabetes, gastrointestinal diseases, cancer and adverse drug reactions. Metabolism may also effect responsiveness to treatment for disease. Metabolism can affect absorption of drugs, hindering or assisting the proper care. The more scientists understand the way in which metabolism affects individual response, the more treatment will be fitted to each person's needs.


Google to preserve a DNA database online

Google recently made an agreement with DNAnexus to maintain a genetic database on the internet. The decision was made after it came to light that the government might not continue funding the database. The database hold many "snippets of genetic data decoded by sequencing machines." While the "Sequence Read Archive" is currently the largest on the web, many assume there will be more extensive collections in the future. As DNA sequencing becomes cheaper opportunities to collect it in mass quantities are more available- such collections are invaluable in comparing archived and newly sequenced DNA. As the article notes, " a year ago it cost $30,000 to sequence a person's entire DNA. [And] today the number's down to $4000." Google has had a longstanding interest in genetic storage, so this move is not surprising. That said, it forces one to consider the ethics of placing such information online. What are the implications of making genetic data accessible via the internet? What new types of risks does that pose? These aren't questions currently being handled by Google, but they are inevitable in the fast moving transformation of genetic storage.


'Sensitivity Gene' predicts reaction to CBT

In class several hot topics have addressed the genetics of anxiety disorders and depression. We know there are two forms of Serotonin Transporter Promoter Polymorphism (5HTPP)- one long, and one short. Now these genes can be used in a study "to predict whether a child suffering from anxiety disorder will benefit from cognitive behavior therapy." After a series of tests, those with a shorter 5HTPP were found to be more likely to benefit from CTB. This is interesting in that longer 5HTPP's are usually shown to be reflective of more positive feelings. But the theory is that if a shorter 5HTPP causes stronger negative feelings, it's reaction to the CTB is more significant. CTB is based on the idea that our thoughts control our feelings and behaviors. Because anxiety is the most prominent disorder among children (10% have some form of anxiety disorder), these findings may prove very valuable.


Sunday, October 23, 2011

I saw this article and thought it might relate to the class. It describes who the discovery of a weapon embedded in a mastodon rib indicates the first example of Pre-clovis weaponry.

Thursday, October 20, 2011

Schizophrenia Genetics Linked to How the Brain Processes Sound


Schizophrenia is a common mental disorder which affects the brain's ability to carry out thought processes and emotional responses.  One percent of Americans are affected by schizophrenia.  Onset of symptoms usually occurs between the ages of 16 and 30 and these symptoms can include:
  • hallucinations
  • paranoia, delusions
  • disorganized speech and thinking
  • social withdrawal and a loss of motivation

The dystrobrevin-binding protein 1, or dysbindin, is a protein found in skeletal muscles cells, lysosomes, and neural brain tissue.  The dysbindin protein in the brain is a constituent of axon bundles and is associated with nerve synapses, and it is this function of the protein that is correlated with schizophrenia.

Schizophrenia and Dysbindin Research

Previous research concerning the dysbindin protein has helped to establish correlations between dysbindin and schizophrenia.  For example, the results of a 2002 research project found that the allele of the dysbindin gene expressed in mice seemed to be associated with the mental disorder.  Thus, certain alleles of the dysbindin gene seemed more likely to result in the onset of schizophrenia.  Another research project in 2009 found that dysbindin helps to control synaptic homeostasis.  As a result, the protein is required presynaptically in the brain.

The newest research on dysbindin and schizophrenia was conducted by the Perelman School of Medicine at the University of Pennsylvania.  The results of the study, entitled "Schizophrenia Genetics Linked to Disruption in How Brain Processes Sound," were published on October 16, 2011 in the Proceedings of the National Academy of Sciences and in Medical News Today.  The goal of the study was to use high-speed imaging techniques to study schizophrenia on a cellular-level, and to better understand how the function of dysbindin affects the phenotypic symptoms of the disorder.  The researchers hypothesized that a reduced amount of the dysbindin protein caused by a mutated gene could lead to schizophrenic symptoms.  To test this hypothesis, in the study mice with a mutated dysbindin gene were exposed to sound and their neural responses were observed.  The mice with the mutated gene expressed sound-processing deficits in the brain.  Nerve cells that usually control fast brain activity became less effective in these mice.  These nerves control brain activity by essentially turning cells "on and off" in order to process large amounts of information.  Thus, in patients with schizophrenia, it is likely that many of their symptoms result from the ineffectiveness of nerve cells due to a reduced amount of the dysbindin protein and this research may lead to new treatment options for symptoms of schizophrenia that are currently untreatable.

Alcohol Flush Reaction

Alcohol flush reaction (aka Asian glow) is caused by a buildup of acetaldehyde

This accumulation is usually caused by a polymorphism of (which leads to a deficiency of) ALDH2, which breaks down acetaldehyde; this deficiency is more prevalent in Asian people (more than 1/3)

One study examined 30 healthy Asian men from UCSD who were 21-25

The study had them drink certain amounts of alcohol and then measured their facial flushing at 30 minute intervals; it also assessed their level of intoxication using the Subjective High Assessment Scale which asks them to rate themselves on 11 items: uncomfortable, high, clumsy, muddled/confused, slurred speech, effects of alcohol, feelings of floating, dizzy, nauseated, drunk and activated

15 of the men were homozygous ALDH2*1, 14 were heterozygous and 1 was homozygous ALDH2*2; all the ones with ALDH2*2 were flushed

All the flushers had higher pulses and also responded more negatively to the questions of clumsiness, dizziness etc.

It’s possible that these intense reactions to alcohol could contribute to a reduced tendency among Asian people to drink excessively

However, many people who are deficient in the gene (esp. those who are heterozygous for ALDH2*1/2) have an increased risk for throat cancer; studies show that ALDH2 deficient people who have 2 beers per day have a 6-10 times higher risk of cancer than people who are not deficient

"Breeding Industry Sees Double as Cloning Takes Off"

In 1997 a group of Scottish scientists at the Roslin Institue successfully cloned a sheep and produced the famous “Dolly.” Dolly’s birth brought on a serious debate about what to do about “cloning”—an term that scientists use to describe the duplication of biological material. Immediately questions arouse surrounding the ethics of cloning because the procedure was often unsuccessful. The debate then centered around whether or not cloning should be used to create a human being—and the answer was a definitive no. Recently, cloning has been mostly out of the media, at least when compared to the media flurry surrounding Dolly and the birth of cloning. However, though it may have been kept out of the public eye, scientists have continued to perfect the cloning process to the point where cloning is now causing debate in a completely different community: the world of polo.

In 2005, in the finals of the world’s most prestigious polo tournament, the Argentine Open, a horse belonging to Adolfo Cambiaso, the undisputed best player in polo, fractured a leg and was put down. The horse, a stallion named Aiken Cura, was Cambiaso’s best horse so, in an effort to save the amazing horse’s genes, Cambiaso ordered the vet to take a sample of the horse’s cells and cryogenically freeze them. Cambiaso later teamed up a cloning company called Crestview Genetics who took Aiken Cura’s cell samples and successfully cloned a foal who was born in Texas last June. Other polo players have followed suit, and cloning has truly changed the game. Cloning does not guarantee that a cloned horse will perform as well as its genetic donor, and consequently most players are cloning their horses for breeding purposes because they are still genetically identical. Cloning a horse costs $150,000, and a good stallion can easily fetch at least $500,000 a year in stud fees. Cambiaso recently sold one of his cloned foals for $800,000.

So what is cloning, and how does it work? There are several different types of cloning, but the main types are: DNA cloning, reproductive cloning, and therapeutic cloning. The type of cloning we are dealing with is called reproductive cloning, which uses the DNA of one animal to generate another genetically identical animal. The process starts with, “somatic cell nuclear transfer” where the genetic material from the nucleus of a donor adult cell is transferred to an adult egg cell whose nucleus has been removed. Then, the reconstructed egg is treated with chemicals or an electric current, which will stimulate cell division. Later, when the cloned embryo reached a stable stage, it is placed into a female host where it will develop until birth. The result is an animal with an identical DNA, perfect for the world of horse breeding.


Alarm Clock” Gene Explains Wake-Up Function of Biological Clock

Researchers at the Salk Institute for Biological Studies have identified a new component of the biological clock, a gene responsible for starting the clock from its restful state every morning. The biological clock works up our metabolism early each day, telling our bodies that it's time to get up. Discovery of this new gene and the mechanism by which it starts the clock everyday may help explain the genetics of sleeplessness, aging and chronic illnesses, such as cancer and diabetes, and could eventually lead to new ways to treat these illnesses.

Does Teamwork Have Evolutionary History?

It has always been speculated whether humans are selfish or whether teamwork is built into our evolutionary history. A Planck Institute funded study recently performed by Yvonne Rekers, Daniel B.M. Haun and Michael Tomasello seeks to reveal whether the tendency to cooperate is purely human or springing from primate’s tendencies. Human societies have always been built on collaborative activities. From childhood, human children are skillful and proficient collaborators and are able to identify when they need collaborators to solve a problem. Primates, specifically chimps, also engage in cooperative activities such as border patrols, group hunting, and intra- and intergroup coalitionary behavior. This study was the first study comparing collaborative motivation between children and chimpanzees, and was based on the hypothesis that a key difference between human and chimp collaboration – potentially a key point in the evolution of human cooperation – is a simple preference for collaborating (versus acting alone) to obtain food. The study gave children/chimps the option of collecting food from a board by either pulling on two ropes simultaneously by themselves, or pulling on one rope and allowing the other rope to be pulled by a partner in another room simultaneously in order to obtain the food. Children used the collaborating option 78% of the time while chimps only used it 58% of the time. This supported the hypothesis, reflecting the human tendency for collaborative foraging manifest in human foraging societies and raising the possibility that humans may have specialized cognitive and motivational mechanisms for collaboration, including collaborative foraging. Collaborative foraging may well have been an important behavioral domain, which humans evolved a suite of new proximate mechanisms, both cognitive and motivational, for collaborating with others in ways that eventually led to the complexities of modern human societies. Further research should compare cooperative motivation across different primate species to try to reconstruct the evolutionary history of the trait. It’s recommended to try it with bonobos, who have been argued to closely match some of the human prosocial motivations.


Genetics, Depression, and Anxiety

5-HTTLPR is a polymorphic region in a region of the 17th chromosome called SLC6A4. This means that different phenotypes can exist in that region. The entire gene codes for the serotonin transporter, but the 5-HTTLPR is part of the promoter region, which regulates how the gene functions.

Serotonin is a neurotransmitter within the body that is used to connect the body’s physical state with mood. For most living organisms, serotonin is released in response to the body’s reaction to the abundance or scarcity of resources. Based on this abundance or scarcity, serotonin is sent to your brain that puts you in an elevated or depressed mood.

So then with respect to the 5-HTTLPR, a SNP occurs in the rs25531 and rs25532 positions. This SNP determines if you have a “short” (S) allele or a “long” (L) allele. Within this region of the gene, the 5-HTTLPR contains several repeats of the same sequence. The short allele causes 14 repeats and the long allele causes 16 repeats.

Research has shown that presence of the long allele causes a higher rate of mRNA transcription for the serotonin transporter, which could have a positive impact on the mood of the individual. Several studies have shown higher rates of depression or anxiety disorders among people with the short allele.

This is an example of a gene-environment interaction, because the impact of the gene is altered in the presence of different environmental situations. It makes sense that a gene-environment interaction would occur since, in all cases, serotonin levels in the brain respond to environmental factors.

This has several applicable implications in the world today. The pharmaceutical industry earns a large portion of its money from the sale of antidepressants. That fact could provide a good explanation for why this polymorphism has been so heavily researched over the last 15 years. 5-HTTLPR could provide an explanation for why antidepressants seem to have such varying impacts on different people. It suggests that antidepressants are more effective in reducing anxiety or depression in individuals who carry the long allele.

This polymorphism has been in the news recently because of a study conducted in the Netherlands which showed that marijuana had differing effects on people with the short and long alleles in the 5-HTTLPR region. It showed that marijuana was more likely to cause/aggravate symptoms of depression or anxiety among individuals with the short allele.

Lock of hair pins down early migration of Aborigines

Using tiny genetic clues found in a 100-year-old lock of Australian Aboriginal hair, an international team of researchers has determined the human migration to Australia took place far earlier than originally thought.  According to DNA analysis from the 1923 Aboriginal hair, indigenous Australians were first genetically isolated around 70,000 years ago, some 46,000 years before populations moved out of Africa and the Middle East to colonize Europe and Asia.

In order to call this dominant theory into question, researchers first had to map and genotype the genome of the Aboriginal hair.  The team then developed a method using patterns of allele frequency and linkage equilibrium to estimate migration rate and divergence times between populations sampled: Aborigine, East Asian, European, and African.  The results point to a longer divergence time between Aboriginal Australians and East Asians than between East Asians and Europeans, suggesting an early wave of migration of Aboriginal Australians and a later expansion wave into Asia and Europe.  Researchers also were able to track levels of the archaic human Denisovan DNA in the different populations and found a much higher concentration in the Aboriginal sample, suggesting a long period of inbreeding due to isolation (isolation resulting from an early migration).

Of course questions and doubts remain (to what extent is one Australian Aborigine in 1923 representative of an entire evolutionary history?), but these pioneering techniques are already shedding light on a very uncertain time in human prehistory.

Wednesday, October 19, 2011

Gene Variant Increases Memory Through Brain Function

A new study from Umea University shows that KIBRA(WWC1) T allele carriers have better memories than non-carriers. Up until now, a 2006 study had reigned in the science world, claiming that while KIBRA T allele carriers showed better memory, non-carriers brain compensated for this discrepancy by overworking their hippocampus. This recent study, performed on 2,230 subjects, proved not only that KIBRA T allele carriers performed better in episodic memory, but that they actually have higher activation of the hippocampus than non-carriers.

In the 2006 study that found this T-variant , scientists screened the entire genome to find a genetic variation linked with episodic memory. Patients who carried the T Allele (TT, CT) in a common C/T polymorphis in the KIBRA gene were shown to have better episodic memory that non-carriers (CC). However, later in the study, 30 subjects were photographed using magnetic cameras (fMRIs) during a memory task, allegedly showing that non-carriers actually had greater activation of their hippocampus than carriers. With this information, the 2006 study concluded that non-carriers needed to compensate for their poorer memory function with increased activation of their hippocampus in order to keep up with the memory levels of T carriers.

The hippocampus is important in this equation because it plays a significant role in the formation of new memories about experienced events(episodic or autobiographical memory). We have 2 hippocampus, due to the bilateral symmetry in our brain, so we can still retain near-normal memory even with one damaged hippocampus. However, if both were to be hemispheres were damaged, the brain would have difficulty forming new memories and retaining old ones (amnesia). Shown in fMRIs, activity in the hippocampus is linked with episodic memories being formed.

The newest study performed recently by Umea University took 83 or their 2230 subjects and did an fMRI scan, proving that non-carriers of the T allele actually have less hippocampus function. After disproving the 2006 study, the conclusion now remains that the T allele plays a role in improving memory by increasing the hippocampus functions.

Websites sited: , ,

Genetic basis of obesity

Sanjena Sathian

So it looks like Raquel and I picked the same topic:

The really interesting thing about this study is that it demonstrates the smaller level at which molecular changes can impact phenotype and individuals' health. FTO is a gene that has been studied for a long time because of its potential links to obesity, type II diabetes and even some other problems including potentially Alzheimers, and funnily enough, webbed toes in mice.

This study has expanded on that FTO link, finding that the allele of FTO that has been linked to higher rates of obesity (or more specifically, larger appetite/propensity for food consumption) is involved in methylization of messenger RNA. This is something that we know happens to DNA a lot, where a certain protein's function is to remove a methyl (CH3) group from a DNA base. But here, it's happening with adenosine on messenger RNA; what's also unique here is that it's reverse methylization, so the FTO protein secreted by the obesity-risk-allele is actually capable of both removing and adding a methyl group to the adenosine base.

If researchers know something about this, they might be able to come up with new and innovative gene-therapy ways of treating lifelong obesity (though many previous studies have indicated that despite a propensity for consuming more, those with the risk-allele of FTO can still exercise and live healthily). In addition, it points to an important new field where studying what is happening even at the base level of RNA is important, so we have to go even smaller than exon splicing etc to understand genetic variation.

Naked Mole Rat Genome May Hold Key to Long Life

To most people, naked mole rats are ugly hairless rodents who live in underground tunnels. Most people don't ever see one outside of an exhibit at the local zoo. But a 2009 study and new research, together, may show that they are useful for much, much more.
Naked mole rats and humans share a surprising number of gene families. The naked mole rat, though, also has a large number of genes which are unique to its species and the unusual characteristics of its species. It is the only cold blooded mammal, and lives in a network of dark burrows and tunnels, with very little oxygen.
It also has some very useful gene variants which lead to very beneficial characteristics. Naked mole rats live into their 30s - sometimes more than 10 times longer than other rodents of their size. They have a strong network of chaperone genes for proteins, better maintain stem cells in their tissues, and are efficient at marking damaged proteins for destruction. Maybe most importantly, they are resistant to cancer.
The recent completion of the sequencing of the full naked mole rat genome may now open up several new doors for research. After the shotgun sequencing process, in which scientists sequenced many chunks of DNA and then aligned them together based on common strings of base pairs, they are now able to study the unique and specialized gene families within the naked mole rat. Researchers say they hope that this will lead to advances in human cancer research and prevention, potential new discoveries in the field of human lifespan increase, and help for victims of heart attack and stroke who, like naked mole rats, need to be able to survive with a severely limited supply of oxygen. The specialized abilities of these tiny bald rodents may be the secret to huge benefits to human health.

Turning On Fetal Hemoglobin: The Key to Reversing Sickle Cell Anemia?


Anemia, joint pain, swollen spleen and frequent severe infections are all common symptoms of Sickle Cell Disease (SCD), a group of inherited red blood cell disorders that result from the presence of a mutated form of hemoglobin, hemoglobin S (HbS). First described by Herrick in 1910, SCD is an autosomal recessive disorder that causes from a single code letter change in the DNA, or point mutation. In turn, this change alters one of the amino acids in the hemoglobin protein: Valine sits where glutamic aid should be. Valine makes the hemoglobin molecules stick together, forming long fibers that distort the shape of the red blood cells that resemble sickles. Sickle cells die early, which results in a constant shortage of red blood cells. Additionally, elongated blood cells get stuck in small blood vessels and clog the blood flow. SCD causes significant mortality and morbidity, particularly in people of Mediterranean and African ancestry.


“For three decades biomedical researchers have hypothesized that fetal hemoglobin could be turned off if the mechanism of hemoglobin switching could be understood.”

New Finding

On October 13, 2011 the Howard Huges Medical Institute (HHMI) published an article that explains how turning on fetal hemoglobin can reverse sickle cell anemia (SCA). An HHMI study led by Dr. Stuart Orkin of Children’s Hospital Boston, Dana Farber Cancer Institute and Harvard Medical School has shown that silencing a protein known as BCL11A can reactivate fetal hemoglobin production in adult mice. In fact, their research demonstrates that BCL11A is one of the primary factors involved in turning off hemoglobin production. In regard to methods of the study Dr. Orkin’s and his team used a genetic manipulation of a mouse model of SCD. A detailed review of the findings, that should further reveal methods used, will be published by Dr. Orkin and his team.


BLC11A could serve as a target for treating SCD and related blood disorders. Of his research Dr. Orkin says: “I think we’ve demonstrated that a single protein in the cells is a target that, if interfered with, would provide enough fetal hemoglobin to make patients better.” However, further research is needed into the working of BCL11A, to determine a model of transference from a mouse model of SCD to a human one.

Evolution: Sugar Helped Separate Human Ancestors From Apes

We know that our ancestors were hunters and thrived on red meat, which gave them a greater risk towards different diseases. Questions are brought up wondering why this lifestyle did not kill them, and what possibly gave them immunity from the pathogens in the many animals they ate regularly.

Scientists at the University of California, San Diego have been studying and researching this question for the past few years. They have concluded that the substitution of one sugar for another is what gave them the immunity from certain pathogens. This is elaborated on further in an article by ABC news.

It is seen in the relationship between ape and human DNA that up until 3 million years ago, they shared the same sugar, but then a slightly different sugar was substituted in humans. The researchers at the University of California , San Diego say that this change in sugar was a result in a mutation of a gene found in humans. This mutation happened in between the time span of walking upright and brain size expansion, around the time that homo erectus emerged.

It is not quite certain why this mutation came about, but it is believed to be environmentally driven, most likely by the risk of malaria.

Because our ancient ancestors were hunters, they were more likely to contract malaria in the environments they were subjected to. This sugar change is thought to have made these ancestors immune to ape malaria. Ironically, this sugar switch is what makes humans vulnerable to a different malaria parasite, which still kills many people each year.

This switch in sugar was further stimulated because around the time of the switch, our ancestors became more hunter-like, eating more red meat, which contains great amounts of Neu5Gc. This is the sugar found in cells of apes, but not humans. These researchers believe that the immune system responded and saw this sugar as something that needed to be destroyed. The change in sugar at the time had a major impact on human evolution.

Common RNA Modification Linked to Obesity

According to an article in "Medical News Today" on October 18th, a team of researchers at the University of Chicago have taken large strides in uncovering the connection between a specific genetic protein and obesity.
In 2007, European researchers studied the FTO gene, located on chromosome 16. They found a connection between one of the gene's alleles and obesity and/or diabetes II. Until now, though, not much else about this gene was known.
The team at U of Chicago (led by Professor Chuan He) has discovered a "reversible RNA modification process mediated by the FTO protein upon biological regulation" (Medical News Today).
In the past, scientists knew that the FTO protein conducted a process called "methylation" during mRNA coding on a rare, specific gene. "Methylation" involves the removal of the methyl group from a nucleic acid. Thanks to Professor He's team, we now know two new things about methylation. First, it is "reversible," meaning that the FTO protein can both add and remove the methyl from the nucleic acid. Second, it is much more common than previously thought. In fact, the FTO protein conducts methylation on a common messenger RNA called N6-methyladenosine, meaning it adds or removes the methyl from the common base adenosine.
The team at University of Chicago determined that methylation plays a crucial role in the human body's regulation of its biochemical equilibrium. In addition, this process is common throughout the mammal kingdom!
This discovery may lead to novel anti-obesity treatments in the future. Although the functional role of this process is not known yet, it opens the door for much more research in RNA epistemology. In other words, RNA is more important that we might have thought!

Monday, October 17, 2011

The Genetics of Happiness: Transporter of Delight

What determines happiness? Many things to be sure, but you might be surprised how much of a role your genes play in shaping your life's satisfaction. A recent article in the Economist details a groundbreaking discovery made about the nature of human happiness. 

Recent years have seen an upsurge in the study of happiness, not simply among geneticists, but also among economists and policymakers. Riding the research trend, a group of scientists from University College, London, Harvard Medical School, the University of California, San Diego, and the University of Zurich examined over 1,000 pairs of twins (fraternal and identical) in an effort to discover the extent to which happiness is associated with DNA. Previous research has used twin studies such as this one to prove the heritability of personality and intelligence. And as it turns out-happiness is also genetic.
The working paper published by the University of Zurich’s Institute for Empirical Research in Economics, “Genes, Economics and Happiness” (found here), has concluded that approximately one third (33%) of the variation in happiness can be attributed to genes.

In addition to conducting the twin study and a genetic association study to determine the influence of genetic variation, the research team took their project a step further. Comparing their results with two previous independent data analyses, they found that those with a transcriptionally more efficient (or longer) version of the serotonin* transporter encoding gene SLC6A4 tend to report significantly higher levels of life satisfaction.

These finds are interesting in themselves, but even more so given its racial implications. All participants in the studies were Americans, but their responses were also broken down by race. The results illuminated the following: White Americans are happier than Black Americans, Asian Americans, and even Hispanics. Interesting or somewhat depressingly predictable? Those with mixed heritage were not included in the results of the study.

However, the report is adamant in its declaration that SLC6A4 does not necessarily “determine” happiness, and that other genes most likely also play a role. The SLC6A4 gene itself only explains less than one percent of the variation in life satisfaction, though all genes together account for a third of total variance. Summarily, there is no one “happiness gene”, and genetic factors in general simply complement, rather than replace the influence of socio-demographic, economic and cultural factors on happiness.

Despite its limitations, the study is groundbreaking in that it is the first to identify a specific gene linked with happiness. Its larger point is well taken- that genes do matter in terms of subjective well-being (which may be a bit of an obvious conclusion). It would be interesting to see research exploring the influence of environmental factors on the relationship between 5-HTTLPR and life satisfaction, as well as research identifying other genes implicated with happiness. 

Bouchez, Colette. "Serotonin and Depression: 9 Questions and Answers." WebMD. Web. 17 Oct. 2011. <>.

De Neve, Jan-Emmanuel, Nicholas A. Christakis, James H. Fowler, and Bruno S. Frey.Genes, Economics, and Happines. Working paper. National Institute on Aging, National Science Foundation, 20 Sept. 2011. Web. 17 Oct. 2011. <>.

"The Genetics of Happiness: Transporter of Delight." The Economist. 15 Oct. 2011. Web. 17 Oct. 2011. <>.