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Genomes Blog Post Assignment: Parkinson’s Disease, by Chase Ghannam

What is the Trait Being Tested?

Parkinson’s disease is here and affecting many people’s lives. It’s the runner-up neurodegenerative disorder making it the second most common disease next to Alzheimer’s disease. In North America alone, more than one million people are affected by it. Parkinson’s disease is distributed among “1% of 55-year-olds and more than 3% of those over age 75”. Altogether, there are more than four million people with PD worldwide(6).

There are 18 chromosomal regions involved in Parkinson’s. However, “[not] all of the identified genes contain causative or disease-determining mutations”(4). For example, alterations in GBA and UCHL1, “do not cause Parkinson disease but appear to modify the risk of developing the condition in some families”(5). The names of the regions are numbered chronologically from PARK1 to PARK18. These names are really nick-names of the underlying regions. For example, PARK6 is really PINK1. Relating to the genes, “we know of 28 distinct chromosomal regions more or less convincingly related to PD. Only six of these specific regions contain genes with mutations that conclusively cause monogenic PD” or “a form of the disease for which a mutation in a single gene is sufficient to cause the phenotype”(4). NIH states that “variations in other genes that have not been identified probably also contribute to Parkinson’s disease risk”(5).

Specifically, “Familial cases of Parkinson’s disease can be caused by mutations in the LRRK2, PARK7, PINK1, PRKN, or SNCA gene, or by alterations in genes that have not been identified”. However, mutations of these genes can happen to people who have not inherited the disease and the causes of these sporadic mutations are unknown. The functions of all the proteins generally are producing dopamine in the “substantia nigra”(5). Therefore, these proteins are a part of dopamine-producing neuron cells and are made in these specific neuron cells. Because these genes produce proteins that produce dopamine, it makes sense that an alteration, variation, or change in the structure of these proteins would lead to a lack of dopamine production in the brain, thus leading to the trait of Parkinson’s disease.

Source: WebMD(8)

Why Get Tested?

Genetic testing for Parkinson’s disease has not been formalized under either the “Movement Disorder Society or any other PD alliance group”. Testing is encouraged for those with “juvenile-onset PD irrespective of family history; early-onset PD with atypical features and/or a positive family history of this disease; or late-onset PD with a strong family history of PD”. Genetic testing is strongly recommended for patients with early-onset PD. This is to help these people “understand their disease and to make informed life decisions”. It has been argued that testing would not change the clinical management of Parkinson’s. However, according to a journal by Christine Klein and Ana Westenberger(4) that is published on pubmed.gov, testing is becoming exceedingly more important in identifying mutations that will lead to more effective treatment routes(4). If the patient wants more effective treatments, testing is a viable option. It is important for understanding how family plays a role in PD. To start, only fifteen percent of those with PD have a family history with ten percent being reported from other sources(5). However, it is still important for those who have relatives with PD to understand how the disease spread through their family. The genes that spread through a family are the aforementioned LRRK2, PARK7, PINK1, PRKN, and SNCA genes. Furthermore, genes that affect Parkinson’s disease are (1) autosomal dominant, (2) autosomal recessive, and (3) autosomal dominant with reduced penetrance. “In clinical practice, however, pedigrees rarely follow that aforementioned well-defined Mendelian inheritance patterns, i.e., they are frequently complicated by reduced penetrance, variable expressivity, and phenocopy phenomena”(4). Because of this and the variability of inheritance patterns across the genes that lead to PD, it is important for people to be aware of family history in order to make an informed decision about testing for PD.

For those who decided to test for PD, I recommend a single-nucleotide polymorphisms test in order to determine whether you have certain variants that “are considered to be [associated] with the disease”(4). The cost to test for all six known genes would cost $4,000 and would not be covered by Medicare(1). The type of test recommended given for the most common alleles for Parkin. Parkin mutations account for “77% of the familial cases with an age of onset [less than thirty years] (Lucking et al. 2000), and for 10%–20% of patients in general”. In addition to Parkin, LRRK2 and PINK1 are more common monogenic forms in which testing is recommended. However, testing is generally discouraged for those without “juvenile-onset PD irrespective of family history; early-onset PD with atypical features and/or a positive family history of this disease; or late-onset PD with a strong family history of PD” as mentioned previously(4). Moreover, there is good evidence supporting a connection between these variations and the trait in question in cases where “many family members affected by Parkinson’s disease”(7). The base risk of PD increases with age as PD typically develops in middle to late life. After identifying the variation, the person’s actual risk is not significantly increased unless the person has a family history of the disease.

Think Before You Spit:

There are scientific reasons that someone should not test for PD. There are no diagnostic criteria for SNPs for PD and therefore should avoid testing unless PD is prominent in the family. Risks of misdiagnosis are increased when these types of tests are taken because of a lack of conclusiveness. “Because there is no conclusive screening or test, patients with very early Parkinson’s disease may not meet the clinical diagnosis criteria. On the flip side, this lack of specificity means that you could be diagnosed with Parkinson’s disease, only to find out later that you have a different condition that mimics Parkinson’s”. Instead of genetic testing, the FDA has “approved an imaging scan called the DaTscan. This technique allows doctors to see detailed pictures of the brain’s dopamine system.” Furthermore, “The results of a DaTscan can’t show that you have Parkinson’s, but they can help your doctor confirm a diagnosis or rule out a Parkinson’s mimic”(3).

Ethical Considerations:

There is always a concern for privacy when it comes to genetic testing. Our genes contain personal biological information, so it is recommended that one doesn’t get tested if (1) it’s not needed or (2) doesn’t live in a nation-state where genetic privacy rights are strongly protected. It is important that you weigh the pro and cons of getting testing especially if the testing could benefit treatment management.

Potential downsides of getting the test include (1) getting results that are not conclusive, (2) increased stress or anxiety from seeing results, and (3) getting misdiagnosed or misinformed. According to Roy Alcalay(1), an assistant professor of neurology at the Taub Institute, “positive findings may induce anxiety among first degree family members (who have a 50% chance of carrying the genetic risk as well), and a fear of discrimination (e.g. for employment or insurance purposes) based on the genetic findings”(1).

Asking the Right Questions Before Getting the Test:

Given the large variability of inheritance, the chances that a child, nephew, or aunt will test positive is largely incalculable. Generally, it would be advantageous for one to determine if the disease is either autosomal dominant or autosomal recessive. However, this method of calculating the probability is not effective because “pedigrees rarely follow that aforementioned well-defined Mendelian inheritance patterns”(4).

Testing positive or negative is often misleading for PD. Oftentimes patients will test positive for PD and either not have or have another disease. For patients with a family history of PD, however, testing positive for PD is an indication that the patient should see a specialist and seek a guided treatment managed with consideration of the additional information from the genetic test. For patients who tested under these similar familial circumstances, but instead tested negatively, it is important that they continue to be aware of their familial risk factors and seek additional information as it becomes available.

If you get a test and would like to share the results with a doctor, it is important that you forward the information effectively. That is to inform your doctor why you got the test and what concerns you had leading up. Discuss with your doctor if there are any recommend steps or additional informative outlets about your test results.

For those who test positive, an additional DaTscan which has been approved by the FDA is recommended so that doctors can collect additional information on the dopaminergic neurons (3). While a positive test does not determine Parkinson’s disease conclusively, it is important that a patient tries to decrease other risk factors associated with the environment. “Exposure to certain toxins or environmental factors may increase the risk of later Parkinson’s disease, but the risk is relatively small”(7). In other words, it is encouraged to avoid toxins, but the effect is small compared to other risk factors that are already at play.

Works Cited

(1) Alcalay, R. N. (2016, April 15). Parkinson’s: risk factors, genetic testing and therapies. Retrieved from http://blogs.biomedcentral.com/on-medicine/2016/04/18/parkinsons-risk-factors-genetic-testing-therapies/.
(2) EurekAlertAAAS. (2007, February 22). Low-cost Parkinson’s disease diagnostic test a world first. Retrieved from https://www.eurekalert.org/pub_releases/2007-02/ra-lpd022207.php.
(3) How Parkinson’s Disease Is Diagnosed. (n.d.). Retrieved from https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/how-parkinson-disease-is-diagnosed.
(4) Klein, C., & Westenberger, A. (2012, January). Genetics of Parkinson’s disease. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253033/.
(5) Parkinson disease – Genetics Home Reference – NIH. (n.d.). Retrieved from https://ghr.nlm.nih.gov/condition/parkinson-disease#resources.
(6) Parkinson’s disease. (n.d.). Retrieved from https://www.snpedia.com/index.php/Parkinson’s_disease.
(7) Parkinson’s disease. (2018, June 30). Retrieved from https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055.
(8) Parkinson’s Disease: Symptoms, Causes, and Treatment. (n.d.). Retrieved from https://www.webmd.com/parkinsons-disease/ss/slideshow-parkinsons-overview.

Project Reflection – Chase Ghannam

Trash coming from a small 10 square foot section in the woods behind apartments and next to a fraternity house.
  1. Joshua Baker and I volunteered at the Carriage Lane site for the Rivers Alive Outreach. We took part in a trash clean-up. Carriage Lane is between the Clarke Garden apartments and the Woodlands of Athens. It is also next to the Phi Kappa Psi fraternity house. Consequently, Joshua and I discovered plenty of litter ranging from empty bags of Doritos to the more prevalent beer bottle and beer can. The Carriage Lane section that I was apart of was further broken up into several teams. We were originally going to be assigned a specific part of the road by the discretion of the leaders, but Joshua and I asked if we could clean up a specific spot. It was in the trees next to the garbage containers and the closest spot to the fraternity house. As a result, there was a lot of trash to clean up.
  2. The location we cleaned up was right next to the garbage container, so I assumed that people would just walk a few feet to that box to discard their waste. However, I was surprised to find out that this area had the most litter not only in its immediate vicinity but also 10-20 feet away. This revelation made me question the social implications of the people living in this area. It led to outward pity and sadness. Furthermore, I am increasingly concerned about the laziness of people and our community as a whole. Athens is public and all of ours to enjoy. Given this, why hadn’t this been cleaned prior to our project? In a larger sense, I am concerned about how numerous this type of negative activity is for America as a whole.
  3. I wish I could say I have hope for the immediate future. Given that Athens is blessed with the environmentally conscious University of Georgia, it can be assumed that the most effort possible is being brought forward to decrease environmental degradation. Litter requires the most menial action to clean up. All you need is gloves, a grabber, and a trash bag. It doesn’t require extensive research or any advanced machinery. If Athens has large amounts of litter even with an active eco-conscious community and programs such as Rivers Alive, then any city could be extensively littered. But that situation is actually not the case and this is where my hope arises: city-planning. With increasing mapping technology, city planners can absorb and note information about where trash piles up. It turns out that litter is dismissed as being solvable by menial action. However, litter clean-ups could be improved from more advanced information. Technology can be used to decrease our environmental pollution and I have long-term hope for those changes.
  4. I enjoyed my time with Josh and my time helping the environment. It felt great to contribute. I was impressed by Rivers Alive as a whole and their ability to locate sites that are in need of cleaning up. However, I am saddened that the litter exists in the first place. This experience also reminds me of the great demand Athens and other communities have for volunteer work, so I will be doing more clean-ups in the future. I will also communicate my concern to people I know so that the word goes around. I hope that Athens and other communities can solve their litter problems and promote a greater eco-consciousness for the world. 

Climate Simulation (EU) – Chase Ghannam

When I played my role in the policy exercise, I felt like our groups’ decisions, while they were generous, did not have a large enough effect on reducing carbon emissions because of other countries’ (America) lack of monetary assistance to developing countries that would allow them to partake in green activities.

We became more generous after negotiating with other countries because we learned that other countries were goal-oriented in reducing carbon emissions. Furthermore, we shifted to being more obliged to donate to developing countries when we were assured our donations would not go to waste.

My group changed its ideas when we got developing countries to agree to increase their committed percentage of an anual reduction of carbon emissions.

That change was prompted when we gave them money that would be used to protect their rainforests from deforestation and to transform their industries into green industries.

I think that emissions can be cut after a lot of effort and awareness, so yes, it is possible to cut emissions.

Some major costs would be the effects of lowering our GDP and other costs to implement regulations such as subsidizing.

We can catalyze change in the US by inspiring change through our example and by showing factual results from our successful efforts.

Chase Ghannam – Photo Reflection

Notice: The shiny metallic objects are tin cans
  1. In this picture, I see the location where Lilly Branch flows into the North Oconee River. Of course, there is some water and some tree branches in the foreground marking what is supposed to be a natural setting.
  2. There are two things that are particularly striking: (1) the lack of water (2) trash. This is a river, so I expected more water to be flowing through it. I also noticed that the cans were situated close to each other (more about that next).
  3. As a result, I would interpret that someone or a group of people had disposed of their cans within a similar time frame and that during the following days the water level was low enough to send the trash towards the North Oconee connection, but there was not enough water to flood the dirt deposit and the cans collected there. I also interpret that the small dirt deposit is a result of Lilly Branch carrying eroded dirt along the stream. When the dirt particulates reach the North Oconee, a perpendicular entry point, a certain amount of dirt having greater inertia cannot successfully turn with river’s direction while maintaining enough velocity to evenly distribute. As the particulates slow they are more susceptible to other forces that go against the direction of the stream. That dirt is then attracted to vortexes (sections of water with a net velocity of zero) which allow the dirt to accumulate. Note that this doesn’t happen to all dirt as water is strong enough to carry most of the dirt along with it with minimal depositing. However, as the water level changes throughout the year, the net effect is an overall accumulation of dirt which is seen clearly in the picture below. Problems could arise if this dirt dam grows.
  4. I feel that many of the answers to our problems are out there. It just takes time and detail-oriented observation to find them.
  5. I think this picture is about the problem of pollution, littering, and poor planning. It shows how interconnected decisions are to seemingly random results (the idea of cause/effect). At least we know where we can find litter for clean-up projects: perpendicular connections.
Note: This is the same as the previous picture; however, it is zoomed out to show the scale of the dirt deposit

Chase Rasem Ghannam – go to US; 30.3195° N, 86.1374° W

My name is Chase Rasem Ghannam. It means Hunter – Reflection – Shepherd. The coordinates above are for my grandparents restaurant in Seaside, Fl (go there for great food). I’ve taken High school Biology, Chemistry (I liked Chemistry the most), and Physics. I appreciate the sciences as my grandfather was an allergist and created simethicone while studying at the University of Michigan. While I am a business major, I plan on continuing my education in science to satisfy my natural curiosity of the brain. I plan on taking a course in some field of neuroscience at some point. For now, I will enjoy learning basic concepts from this class that should lead me to a greater understanding of future options of interest relating to this field. As a student, I am interested in the Outfall Inspections project as I am curious to learn the process of a scientific inspection and how it might relate to business practices of financial data collection and even analysis. I would like to gain a greater understanding of how connected the sciences are to civic engagement outside of sustainability efforts commonly publicized. I want to learn more ways to connect Biology to business and have a personal knowledge set where I can create more connections.