Twins on Trial

When someone hears of twins, their mind usually flies right to the thought of two individuals that look alike and 50% of the time you would be right. There are two different types of twins: fraternal and identical. Fraternal twins are what you would call dizygotic twins. This means during fertilization there were two eggs produced and fertilized. These twins develop within separate placentas and usually come out looking different. On the other hand identical twins, or monozygotic twins, happen when one egg is fertilized and splits into two embryos. These twins share the same placenta and are born exact replicas.

Now with this information in mind, let's bring it down to a more molecular level. Monozygotic twins share the exact set of DNA since they are in a sense replicas of one another while fraternal twins have their own specific set of DNA. So with all the fun things that happens to our DNA throughout our lifetime, DNA methylation is really neat. This is the process when DNA methyltransferase (pretty neat name because it literally gives you a hint for what I'm about to say it does) adds a methyl group on the 5' position of the pyrimidine ring of the cytosine nucleotide. This methylation usually only occurs when there is a cytosine followed by a guanine. You might be familiar with the term CpG sites. Methylation is a cool process that usually affects the nature of a gene; it acts like a switch to turn active genes off or, during stem cell differentiation, methylation helps guide the stem cell to become a certain type of cell based on the methylation pattern. In mammals, this methylation happens pretty uniformly but the patterns can be variable from person to person based on the different environments we have encountered throughout our lifetime.

I probably have you asking by now what does methylation have to do with twins, well my friend, CRIME. We have always been told that if a biological sample is found a scene that holds DNA that that DNA can be sequenced and a suspects DNA can be sequenced to form a match with a high statistical probability. While this is true, it isn't so much true in the instances where monozygotic twins are involved for obvious reasons. Researchers have thought of a sort of solution, while it isn't perfect and there is a lot of testing to be done, of taking a look at not only the DNA but of the DNA methylation patterns to differentiate between the two individuals. The study is based on the principle that the methylation patterns will be different because the two individuals, even though they are twins, could have experienced different environmental stimuli at one time or another in their lifetime.

Using melt curve analysis Stewart et al. tested this hypothesis at the Alu sites of 5 sets of monozygotic twins. Alu sites are highly conserved throughout the human species and they are what you would call a short interspersed nuclear element meaning that they are about 300 nucleotides long and the nucleotides are in a repeated sequence (these sites are commonly mutated because of the repetition). Even though this method seems pretty solid, it is very variable. One set of twins did show a large differentiation between their methylation patterns while the others showed subtle or no differences. Age and environmental stimuli play a huge role for the success of using this kind of study. While the test itself is relatively cheap, the results might not be substantial for the use in a court of law. If anything, it could be used as a preliminary test before moving on to the more expensive mutation tests in a forensic laboratory. I believe that this there are other sites that could be tested for the differences in methylation that might yield more substantial results. On the other hand, a larger pool of twins might need to be used in order to get a truer result.

For further reading: http://www.sciencedirect.com/science/article/pii/S0003269715000500

Feet and the GDF6 Gene

Feet. No one talks about them because honestly, they are kind of gross. For humans, having feet is an advantage, our big toe especially, because without them we wouldn't be able to walk normally. Bipedalism has thought to have occurred because of the formation of our big toe throughout the evolution of humans. So what may have caused the creation of the big toe in our earlier ancestors?

Bone morphogenic proteins are molecules that control the formation of bones and joints during development. These proteins have been suspected to be the cause of evolving new structures while preserving the function of old structures. By first looking at the drastic differences in the freshwater and salt-water species of stickleback fish using genetic mapping of skeletal traits, Indjeian and his colleagues were able to find that cis-acting increase of the Growth/Differentiation Factor 6 was involved in the difference in amor plates in these fish, meaning that the freshwater species shows smaller plate size as they evolved due to the increase of GDF6. Smaller plate size has benefitted the freshwater species by facilitating in faster bursts when swimming but what does this have to do with the evolution of bipedalism in humans?

As humans evolved, multiple changes were made to benefit the species. For example, as locomotion started for humans, the hindlimb toes started to shorten and the strengthening of the first digit, our big toe. It was shown that the GDF6 gene is responsible for normal growth of the digits and the expression decreases as it moves away from the first digit, that is why our other toes are so much smaller than our big toe. This gene is also responsible for skull sutures and eye development. Deletion of a region-specific enhancer allowed this gene to alter the structure of the hindlimbs over time to adapt to the ever-changing environment without negatively impacting forelimb development. This enhancer deletion is human-unique as it is still prevalent in primates and other mammals. 

For further reading: Indjeian, Vahan B., Garrett A. Kingman, Felicity C. Jones, Catherine A. Guenther, Jane Grimwood, Jeremy Schmutz, Richard M. Myers, and David M. Kingsley. "Evolving New Skeletal Traits by Cis-Regulatory Changes in Bone Morphogenetic Proteins." Cell 164.1-2 (2016): 45-56. Web.

Methylation Markers Used to Identify Body Fluids

Each individual has their own unique genetic fingerprint and in the instance a crime has occurred, this genetic fingerprint can be useful in identifying perpetrators or even link victims to the original crime scene in an instance that the body was moved. The journal article Methylation Markers for theIdentification of Body Fluids and Tissues from Forensic Trace Evidence poses the question if there are specific methylation markers on DNA that can identify with positivity what type of bodily fluid is present at a crime scene and if exogenous or endogenous factors skew the methylation.

I found this research interesting because it was one of the first to actually take into account the exogenic and endogenic changes that body fluids come into contact with at a crime scene. The study's goals were to describe an epigenetic marker set using methylation on regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide (CpG sites) for venous blood, menstrual blood, vaginal fluid, saliva, and sperm. These body fluids were chosen specifically because they are the most prevalent at a crime scene. Their hypothesis stated that because many methylated loci are involved in cell-specific gene expression, quantifying the degree of methylation at these positions could identify a cell line with accuracy.

Within the research Forat et al. tested different variables that the body fluid could undergo at a crime scene and their effects on the methylation by first finding reciprocal marker loci. This means that they wanted to find loci for which the target body fluid was unmethylated while the remaining fluids' loci were methylated. After the markers were located, the body fluids were placed in sample environments: dry on room temperature, wet in an exsiccator, outside on the ground. Each sample was tested after 1, 2, 3, and 6 months.

The discrimination power of these markers are very high because in all cases there is at least 1 marker for each kind of fluid and they show no overlap distribution of methylation rates compared to each fluid. Thus showing that each of the body fluids can be positively identified using the method explained in the article. The researchers even went on in explaining influences that made the results less clear. A large example was that tumors have an effect on the methylation patterns in women with cervix cancer.

This research is significant in the field of forensic science because it moves away from using RNA to identify body fluids since RNA is less stable in a variety of different conditions. Another surprising result was that each time a body fluid was examined, even when the body fluids were mixed, the method identified the fluids 100% of the time. 

THC: The Future of Alzheimer's Disease

Alzheimer's Disease is the 6th leading cause of death among Americans and it affects over 20 million people. Finding a cure has been impossible for scientists, as they have only found a way to slow the disease down. It is imperative that a cure be found so people and loved ones will not have to go through this debilitating disease.

In brief, Alzheimer's is a disease that destroys memory and other cognitive functions. In the brain neural cells die and in turn the brain starts to loose tissue mass. Plaques are also built up in the Alzheimer brain. Proteins called beta-amyloids are a prime component of these plaques because they are sticky and tend to aggregate, or collect together. These aggregates surround the nerve cell and are hypothesized to be the main reason for the neural cell death.

Recently, studies have shown a molecular connection that cannabinoids, more specifically THC, to have therapeutic benefits for Alzheimer's Disease. Before the study by scientists at the The Skaggs Institute for Chemical Biology, THC was only tested to have effects downstream as signaling molecules in the pathology of the disease and not correlated to have any affect on the beta-amyloids. The pathology of Alzheimer's has been extensively studied and it shows that the acetylcholinesterase (AChE) enzyme acts as a chaperone in forming amyloid fibers in the brain and forms stable complexes with beta-amyloid at sites called peripheral anionic binding sites (PAS). Since there are already medicines that are out there that work on the inhibition of the AChE active site, it was hypothesized that THC, with its fused tricyclic structure, could bind to the PAS of AChE and prevent AChE-promoted beta-amyloid aggregation.

From this study it was shown that THC competitively inhibits the AChE within mice, which diminishes aggregate formation. This was noteworthy because at a molecular level the THC molecule actually played a role in impacting the disease pathology and it is shown to be a better competitor than the already marketed drugs at half the concentration. In the future THC could be a therapy that not only treats the symptoms of Alzheimer's but also the progression of this debilitating disease.

What are your thoughts on using THC as an therapy for Alzheimer's? Do you think that the the drug's strong affinity for the cannabinoid receptors in our body will be costly to the therapeutic effects that this drug promises?

For further reading on this study and how the scientists came to the conclusion: http://pubs.acs.org.ezproxy.shsu.edu/doi/pdf/10.1021/mp060066m