Category: Genetic Testing Blog Posts

Should You Get Genetic Testing for non-Hodgkin Lymphoma?

By Marianne Lamarche

This year, an estimated 74,200 people in the United States will be diagnosed with non-Hodgkin Lymphoma, the seventh most common cancer in both men and women. With an overall five-year survival rate of only 71%, this cancer poses a devastating threat to the health of thousands every year. As genetic testing technology flourishes, however, scientific advances are providing hope for lymphoma and other similar diseases. Here is everything you need to know about the groundbreaking technology and what it means for you and your family.

A 2006 study by the National Cancer Institute found that SNPs in two genes, tumor necrosis factor-alpha and lymphotoxin-alpha, were associated with a 1.31x increase in non-Hodgkin lymphoma. These genes affect inflammatory and innate immune responses, which can result in patients with lymphoma struggling to fight off infections. This could make the patients disastrously sick, so doctors searched far and wide for a way to detect these genes as early as possible.

Image result for non hodgkin lymphoma graphic

Recently, the Mayo Clinic became the first in the US to offer genetic testing for Lymphoma. While the clinic did not describe exactly what type of test this entails or how much it would cost, the director of the Center for Individualized Medicine at the Mayo Clinic has stated its appeal. “Diagnostic tests such as the Lymph2Cx test will address an unmet need of cancer patients in the U.S. and worldwide,” Dr. Stewart said. “New tests like this help us identify accurate diagnoses and treatments quickly, saving time and money, and, ultimately, transforming patient care.” By studying gene expression and mutations, doctors may be able to more clearly define which patients will respond best to certain therapies, potentially allowing them to treat patients without intrusive chemotherapy.

But we have to consider that these new discoveries still have some limitations. The research on the proinflammatory cytokosine genes listed above was associated with a marked increase in non-Hodgkin lymphoma, but other variations that impact the trait might remain unknown. In general, more research needs to be conducted, as the researchers themselves stated that their “results require replication”. Due to the relatively new nature of these studies, genetic testing might not be the best idea for everyone, since there is so much left to learn about these genes and their impacts on non-Hodgkin lymphoma, and the results of the testing could be misleading.

Results of genetic testing for non-Hodgkin lymphoma could also have some adverse ethical consequences. Dr. Staudt, the lead author of a 2018 study from the New England Journal of Medicine, believes that lymphoma patients should discuss the pros and cons of genetic testing with their oncologist. As cancer research is still in developmental stages, there may not be drugs available for every mutation found in lymphoma patients. In this scenario, their best option for treatment could still be chemotherapy. However, for patients not yet diagnosed with lymphoma but who fear they might be susceptible to it in the future, genetic testing could help them discover if they possess the genes that are associated with an increased risk for non-Hodgkin lymphoma. This also has ethical considerations, though, because if they find out they possess the gene, they might develop chronic stress and experience a decline in their quality of life, whereas even if they discover they don’t possess it, there are so many other branches of lymphoma that they might still become sick despite their efforts to be proactive. 

Family history does not have a strong impact on the likelihood of contracting lymphoma; it isn’t currently found to run in families, although your risk might be slightly increased if a first-degree relative has had lymphoma.Thus, you may want to get this genetic test if a parent or sibling has had lymphoma in the past. If you do test positive, however, there are a few lymphoma risk factors that you should avoid to decrease your chances of becoming ill. Medical conditions or treatments that weaken the immune system, such as HIV or post-organ transplant medicine, autoimmune conditions, the Epstein-Barr virus, a Helicobacter pylori infection, having received chemotherapy or radiation for another cancer, or having celiac disease are all associated with an increased risk of developing the condition. But because most of these factors aren’t under your control, the most important reaction to a positive test would be to see an oncologist frequently to detect lymphomatic cells ASAP.

Genetic testing for diseases is a new, potentially life-changing field, but it must continue to develop in order to fully help as many people as possible without infringing on medical and personal privacy and rights. In the case of lymphoma, it is encouraging that new tests may be able to identify the best and most effective treatments for patients, although the lack of control over developing the disease reduces the impact of proactive genetic knowledge. There is still much work to be done – but thankfully, researchers are on the right track towards a healthier, brighter future for you and everyone you care about. Make sure to keep visiting your doctors regularly, maintain a healthy lifestyle, and stay up-to-date on new medical options available. These steps will help to ensure the best outcome possible for your health and wellbeing!

References

Causes: Non-Hodgkin Lymphoma. (2018, October 19). Retrieved from https://www.nhs.uk/conditions/non-hodgkin-lymphoma/causes/.

Katus, S., Roan, S., Raeburn, P., Steele, M. F., & Takeda, A. (2018, April 20). Genetic Testing Reveals Many Different Types of Lymphoma. Retrieved from https://www.everydayhealth.com/lymphoma/treatment/genetic-testing-reveals-many-different-types-lymphoma/.

Lymphoma – Non-Hodgkin – Statistics. (2019, February 28). Retrieved from https://www.cancer.net/cancer-types/lymphoma-non-hodgkin/statistics.

Lymphoma. (2009, December 1). Retrieved from https://www.snpedia.com/index.php/Lymphoma.

Mayo Clinic first in U.S. to offer genetic test for lymphoma. (2019, May 30). Retrieved from https://www.mayo.edu/research/forefront/mayo-clinic-first-us-offer-genetic-test-lymphoma.

Wang, S. S., Cerhan, J. R., Hartge, P., Davis, S., Cozen, W., Severson, R. K., … Rothman, N. (2006). Common Genetic Variants in Proinflammatory and Other Immunoregulatory Genes and Risk for Non-Hodgkin Lymphoma. Cancer Research, 66(19), 9771–9780. doi: 10.1158/0008-5472.can-06-0324

Genetic Testing for Bipolar Disorder

By Hailey Maxwell

What Is Bipolar Disorder, Actually?

Bipolar disorder, also known as manic-depression or major affective disorder, is found in approximately 4 percent of the adult human population (Comer & Comer, 2018). There is a strong biological basis for this disease, including a genetic predetermination towards developing it. The risk increases to up to 10% if a close relative has the disorder. Among identical twins, the concurrence is between 40 and 70%. Additionally, children of men who were above the age of 40 at the time of conception are 6 times more likely to develop the disorder, which is thought to be because as men age, they have more mutations in their sperm (Comer & Comer, 2018). It is not known how many genes impact one’s likelihood of developing bipolar disorder. Many genes have been found to, in combination, increase one’s risk. Genes on 12 chromosomes have been linked to bipolar disorder (Comer & Comer, 2018). 

The Genetics of Bipolar Disorder

A specific gene involved in bipolar disorder is GRM7, which codes for proteins at the receptor sites for the neurotransmitter L-glutamate, an important excitatory neurotransmitter in the central nervous system (Jun et al., 2014). The mutation in GRM7 that is tested for in genetic testing is a deletion that affects the structure of certain neurons, preventing them from receiving the neurotransmitter glutamate (Escamilla & Zavala, 2008). This prevents these neurons from firing properly.

The best-known genetic test for bipolar disorder is the Autism spectrum/hyperactivity/bipolar disorder, GRM7 related test. The test costs $399. It tests for the deletion or duplication of the gene (Doheny, 2008). However, there are so many genes involved in bipolar disorder that this one test will not be very informative as to one’s risk of developing the disorder. When considered along with race and family history, the results of the test are more informative. The group for which the test is most informative is white people of Northern European ancestry who have a family history of bipolar disorder. If the test comes back positive, this group is 3 times as likely to develop the disorder (Doheny, 2008). However, when considering that the rate among the general population is only 4%, an increase by a factor of 3 only raises the risk to 12%. 

Should You Get Tested?

My recommendation would not be to get this, or any other, test for bipolar disorder. There are too many genes involved in the disorder for any one to be able to make a significant difference in the risk of developing the disorder and there is no test that can test for enough of the genes to be a good indication of whether someone will develop it. Even if this were the only gene that contributed to this disorder, a positive result on the test only marginally increases one’s risk. Even if the test were free, it would still not be recommended, but for the price of $400, I do not suggest taking this test. Instead, if you are concerned about your mental health, treat yourself well. Avoid stress, caffeine, and alcohol or other drug use. Exercise, sleep and eat well, and keep a consistent schedule (Healthwise Staff, 2018).

I Got Tested. Now What?

If you decide to go through with the test and you test negative, you do not know anything more about your risk of developing bipolar disorder. You may or may not have a mutation in a different gene that increases your risk. If you test positive, do not be overly concerned. Your risk of developing the disorder is still very low and the odds are that you will not suffer from bipolar disorder at any point in your lifetime. If you are still concerned that you will develop bipolar disorder, it is best to reduce your stress. Other than biological causes, stress is the largest agitator of bipolar disorder (Comer & Comer, 2018). It is also recommended to reduce alcohol and other drug use, as many of these substances heavily impact one’s moods and can potentially influence the development or treatment of a mood disorder.

It is suggested that you share the results of this test with your therapist, especially if you are in treatment for major depressive disorder. Bipolar disorder is often misdiagnosed as major depressive disorder when the patient has not yet had a serious manic episode. Sharing with your therapist that you are at heightened risk for bipolar disorder is recommended so that he or she may keep a closer eye out for manic behaviors and be quicker to treat them if they appear. 

Sources:

Comer, R. J., & Comer, J. S. (2018). Abnormal psychology.

Doheny, K. (2008, June 4). At-Home Bipolar Disorder Test: Accuracy, Diagnosis, and More. Retrieved November 13, 2019, from https://www.webmd.com/bipolar-disorder/features/at-home- bipolar-test-help-or-hindrance#1

Escamilla, M. A., & Zavala, J. M. (2008). Genetics of bipolar disorder. Dialogues in clinical neuroscience, 10(2), 141–152.

Healthwise Staff (2018, September 11). Bipolar Disorder: Preventing Manic Episodes. Retrieved from https://www.healthlinkbc.ca/health-topics/ty6584.

Jun, C., Choi, Y., Lim, S. M., Bae, S., Hong, Y. S., Kim, J. E., & Lyoo, I. K. (2014). Disturbance of the glutamatergic system in mood disorders. Experimental neurobiology, 23(1), 28–35. doi:10.5607/en.2014.23.1.28

Familial DNA Searches

DNA has been used as a form of evidence for years and is now accepted as one of the more reliable ways of connecting a person with a crime. However, recently police have begun using familial DNA to identify suspects without having an exact match for their DNA. This brings with it several legal and ethical issues, which we’ll talk about.

What has past testing looked like?

  • The Combined DNA Index System (CODIS) is software to store DNA from convicted felons and use it to identify whether any of that stored DNA matches an unknown sample.
  • They match alleles at 13 specified locations in the samples and depending on the strength of the tests, it must match a certain number of the locations.
  • A typical test used to identify a suspect is at the strongest level, where all 13 must match.1
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What is Familial DNA Search?

  • A familiar DNA search uses a different software to list the likely candidates for close family relations and ranks them, then using lineage testing to confirm close candidates.
  • This is different than partial matching, which simply identifies candidates who only meet a certain level of matches STRs without using lineage testing.
  • Y-STR testing, one form of lineage testing, looks specifically alleles on the Y-chromosome which allows you to look at fraternal connection. This highlights one of the current drawbacks of familial searching, which is that it currently can only identify male relations.1
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When is familial DNA testing used?

  • Familial DNA is used only as a last resort when no other DNA testing has worked thus far. It also has typically only been used for major cases.2
  • Familial DNA is also an expensive option for labs—Y-STR testing is currently not regularly used in normal testing, so the additional tests must be purchased for familial DNA. Additionally, much of the current software is slow, making the process use up valuable time and resources, and must be purchased or developed in house by a jurisdiction.3

What are some of the concerns about Familial DNA?

  • The first major concern about familial DNA searches is that it violates your 4th amendment privacy rights. While many accept that upon being convicted for a crime, you give up some of your privacy rights which allow for collection of criminal DNA, it is not widely accepted that those rights apply to your family. By using criminal DNA to conduct familial DNA searches, you are infringing on the rights of family members.
  • The next major concern is that familial DNA is discriminatory, since there is a larger pool of samples for African Americans since they are more likely to be incarcerated and have DNA samples collected. This would make it easier to find matches for African American suspects versus other races.2

Familial DNA searches could make DNA searches for criminals vastly more effective, with one study seeing a 40% increase in the likelihood of finding a relative for an unknown DNA sample through this method versus finding a direct match through traditional methods.4 However, I believe that we have not had the technology advances or worked through the legal implications of familial DNA searches enough to widely implement this process.

Our current methods don’t offer any equivalent for Y-STR testing which would help identify female relations, so we currently must rely on partial matches only. Additionally, fourth and fourteenth amendment rights are at stake, and we need to have a national discussion on how to protect those rights before implementing familial DNA searches widely. Still, in the famous cases which have already used this method, including the Grim Sleeper case, it is already clear that is certainly has the potential to find new, so far unidentified subjects to some of the most puzzling cold cases still open today.

1. National Criminal Justice Reference Service. Understanding Familial DNA Searching: Policies, Procedures, and Potential Impact, Summary Overview. 251043. August 2017. By Sara Debus-Sherrill and Michael B. Field.

2. National Criminal Justice Reference Service. Study of Familial DNA Searching Policies and Practice: Case Study Brief Series. 251081. August 2017. By Michael B. Field, Saniya Seera, Christina Ngyuen, and Sara Debus-Sherrill.

3. National Criminal Justice Reference Service. Study of Familial DNA Searching Policies and Practices: Cost Simulation Tool User Guide. 251045. August 2017. By Avi Bhati and Sara Debus-Sherrill.

4. Frederick R. Bieber, Charles H. Brenner, & David Lazer. (2006). Finding Criminals through DNA of Their Relatives. Science, 312(5778), 1315.

Genetic Testing for Colon Cancer

By: Stephen Foernsler

What causes it?

Colon cancer is very prevalent in the United States with over 90,000 new cases each year. A person has about a 6% chance of contracting it without a hereditary history, and of those with colon cancer about 95% are sporadic and not hereditary. Of course, all cancers are heavily impacted by environmental factors, but colon cancer specifically has a high inheritance risk compared to many others. Many genes are involved with this such as MSH2 and MSH6. These genes are both located on the second chromosome and work to repair errors in DNA replication when working normally. Colon cancer is caused when there are mutations in these genes that prevent them from functioning normally. A major syndrome associated with this issue is Lynch Syndrome which is the most common hereditary form of colon cancer through inherited mutations, and having the gene associated with this gives about an 80% chance of getting cancer. It also increases a person’s risk of other cancers such as kidney or stomach.

Why genetic screening?

Genetic screening is a way to look at your own genes and see if you have any mutations that could lead to medical issues such as colon cancer. Many companies such as 23andMe require just a small spit sample to obtain your DNA and then they could look specifically look at the genes related to colon cancer for prices as low as $100. 23andMe looks specifically at the MUTYH gene that also relates to Lynch Syndrome. This can be a great way to give yourself information about yourself and understand what could hurt you. The average colon cancer rate is about 6%, but those with Lynch Syndrome have up to an 82% risk. For many people this could be the difference between life or death because this knowledge would show how they must get checked much more often for colon cancer. A positive test for a mutation will let anyone know they need to get colonoscopies much more often others or even get stool samples tested through new companies such as Cologuard. People are much more likely to make changes to the environment in a healthier way if they know they are naturally predisposed to get colon cancer, so these tests serve to give people tools to do all they can to limit this disease. Someone without any familial history does not necessarily need this test as they will not have the chance of inheriting that someone with history has. If a person knows of a parent or older relative who had colon cancer, it is a good idea to get tested in case it was from a mutated MSH2 or other gene. 

What are the possible cons?

While this availability of knowledge seems great, there are many downsides that come with genetic tests. One major one is that a negative test for an MSH2 mutation does not mean you cannot get colon cancer. This could cause people to believe that they do not need to keep up with colonoscopies or other tests if they are not fully informed which is very important to know what exactly is going on. Also, having the mutation does not mean getting cancer is inevitable. A positive test result could cause some undue worry for the person testing as well as those around them. This only serves to make life worse and full of stress rather than freeing things up. It is possible other diseases or DNA mutations can be found in genetic tests that a person may not want to know about because it is one that nothing can be done about. Genetic testing is not something to be done lightly and must have much thought put into it. A genetic counselor or physician is also there to help guide people through the process to ensure they understand what is involved with genetic testing and what the results mean. They are there to make it clear what a positive or negative outcome would mean and limit the stress that can come with genetic testing.

Sources

What are the benefits of genetic testing? – Genetics Home Reference – NIH. (2019, November 12). Retrieved November 13, 2019, from https://ghr.nlm.nih.gov/primer/testing/benefits.

Collier, R. (2012, May 15). The downside of genetic screening. Retrieved November 13, 2019, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348188/.

What Causes Colorectal Cancer? (n.d.). Retrieved November 13, 2019, from https://www.cancer.org/cancer/colon-rectal-cancer/causes-risks-prevention/what-causes.html.

MSH2. (n.d.). Retrieved November 13, 2019, from https://www.snpedia.com/index.php/MSH2.

National Center for Biotechnology Information (US). (1998, January 1). Colon cancer. Retrieved November 13, 2019, from https://www.ncbi.nlm.nih.gov/books/NBK22218/.

Athletic Ability

Nico Fontova

            Hard work and talent are two central components to athletic performance. It is crucial for a world-class athlete to be laser-focused committed to improvement, but hard work alone will not determine success. Whether we like it or not, talent—or genetics—influences athletics, but how exactly does it do it?

            There are over 150 genes found to be associated with athletic performance, but most do not have a large enough or statistically significant effect. Two genes in particular play a larger role in athletic performance and building certain types of athletes: ACTN3 (on chromosome 11) and ACE (chromosome 17). The ACTN3 gene creates alpha-actin-3, a protein which is part of the composition of fast twitch muscle fiber.1 Fast twitch muscle fiber is one of two fibers in muscle. It can contract very quickly but also tires quickly and is key to our ability to sprint. Slow twitch fiber is the other; it contracts slowly but has much more endurance.1 The mutation impacting ACTN3 is a SNP (a change of one base to another in the DNA sequence) which changes an amino acid into a stop codon, halting or entirely stopping alpha-actin production. This mutation is shorthanded with an X (for the premature stop) and the normal version is written as an R (for arginine, the original amino acid). Homozygous individuals are RR or XX, while heterozygotes are RX. XX individuals completely lack production of the protein, and therefore much less fast twitch muscle fiber. The XX allele is common in endurance athletes, while the RR and RX alleles are more common in short distance sprinters. The ACE gene codes for a protein which primarily regulates blood pressure, but also influences muscle function in an unclear way. The mutation in this case is an insertion called ACE-I, which is prominent in endurance athletes. ACE-D is the allele without the insertion, and DD and ID athletes are more likely to be sprinters.1,3 These are the genes the influence athletic ability, and it is clear that being RR is more beneficial to sprinters, but is being an XX homozygote give you an advantage in endurance events? And if so, can people use genetic testing to determine their endurance ability?

            Genetic testing for ACTN3 and ACE mutations could possibly be an indicator of your athleticism and could be used to identify future sprinting or endurance talent in young people. 23andMe tests for both genes, so a SNP Chip would be the recommended test, but using these tests as absolute evidence for endurance ability is risky. 

  • A University of Bristol study found the ACTN3 R allele to be associated with sprint performance in Europeans but did not find the X allele to improve endurance ability.4
  • Another study found that only 20% of elite North American and European distance runners studied were XX homozygous, which is slightly higher than the control group at 17.5%.5
  • There clearly is some benefit with the genes, however, as a Swedish study found that only three out of 46 Spanish distance runners tested had a perfect genotypic profile for endurance (including ACE-I and ACTN3-X), but they were among the best in the world.6             

XX homozygotes seem to have a slight advantage in endurance events (in that they are the best of the best in the Swedish study), but it is not a large or possibly notable advantage. Testing for these genes is clearly helpful in determining muscle performance, but they cannot predict someone’s proficiency in a sport by themselves, which could be unethical if taken too far.

            This trait does cross many ethical lines, except for possibly using the test to select children and train children from a young age for certain disciplines. Both ACE and ACTN3 are not the sole predictors of athletic performance, however, so making a child a distance runner because he is II or XX would be wrong; it is important for someone to do what they like and not necessarily what they would be genetically proficient in. Many other factors play into athletic ability including a healthy training environment and eagerness to improve, which may not be present if someone is being forced to train because of genetics. An X or I positive test would affect a sprinter more because they would have less fast twitch muscle fiber in their bodies than others and be at an actual and proven disadvantage. One could use testing to see if they would be good short distance athletes, but most people have the R alleles that account for sprinting ability (around 20%-100% of each studied ethnic group in SNPedia), suggesting that the test is really only useful in current sprinters to see if they are at a genetic disadvantage by being RX.2 This test can be used to measure athletic ability, but a VO2 Max test (a test of the max volume of oxygen the body can use under stress) would be much more useful in determining current athletic ability, while genetic testing could determine potential ability.

            If you test positive for the I or X alleles, maybe you should try your hand in endurance running, or if you already run, feel reassured in your choice, but don’t sweat it too much (unless you plan on being a world class 100 meter runner) because plenty of elite distance runners are RR or RX, and athletic ability is about more than just two genes.5,6 In my opinion, parents should not test their children specifically for this gene or use the results to predict anything because there are many other factors contributing to athletic ability, and the evidence is not solid enough to prove that someone has talent for endurance event because of these genes. ACTN3 and ACE are indicators of how fast you can move, but they are not the whole story and certainly should not be treated as such.

References

  1. Is Athletic Performance Determined by Genetics?. U.S. National Library of Medicine Web Site. https://ghr.nlm.nih.gov/primer/traits/athleticperformance. Updated November 12, 2019. Accessed November 14, 2019.
  1. Rs1815739. SNPedia Web Site. https://www.snpedia.com/index.php/Rs1815739. Updated December 6, 2018. Accessed November 14, 2019.
  1. Rs1799752. SNPedia Web Site. https://www.snpedia.com/index.php/Rs1799752. Updated January 6, 2018. Accessed November 14, 2019.
  1. Alfred T, Ben-Shlomo Y, Cooper R, et al. ACTN3 genotype, athletic status, and life course physical capability: meta-analysis of the published literature and findings from nine studies. NCBI, 2011; Abstract. https://www.ncbi.nlm.nih.gov/pubmed/21542061?dopt=Abstract. Accessed November 14, 2019.
  1. Döring FE, Onur S, Geisen U, et al. ACTN3 R577X and other polymorphisms are not associated with elite endurance athlete status in the Genathlete study. NCBI, 2010; Abstract. https://www.ncbi.nlm.nih.gov/pubmed/20845221?dopt=Abstract. Accessed November 14, 2019.
  1. Ruiz JR, Gómez-Gallego F, Santiago C, et al. Is there an optimum endurance polygenic profile? NCBI, 2009; Abstract. https://www.ncbi.nlm.nih.gov/pubmed/19237423?dopt=Abstract. Accessed November 14, 2019.

Marfan Syndrome

Marfan syndrome is a genetic disease that affects the body’s connective tissue. People with the disease tend to be extremely tall and slender. This disease affects about 1 in every 5,000 people [1]. Marfan syndrome is typically caused by a mutation in the FBN1 gene which affects the way in which the protein fibrillin-1 is made. The production of the protein is enhanced and the surplus in fibrillin-1 is what harms the connective tissue, ultimately causing problems all over the body. Because Marfan syndrome causes complications throughout the body— such as in the heart, bones and joints, lungs, and nervous system— it makes sense that the FBN1 gene variation is what causes the disease [2].

[7]

Why and How to Test

            Testing for Marfan syndrome is very important if you think there might be a chance that you have it. This is due to the fact that even if the symptoms are not always life threatening, they are detrimental to your way of life. If you find out that they are a result of Marfan syndrome, you can be more cognizant of the way you go about life so that you can live up to the normal life expectancy that the disease usually entails. For example, having Marfan syndrome would make it dangerous to play contact sports, both because of the brittleness of your bones and the higher risk you have for heart enlargement and heart failure as a result of that. The most effective and efficient form of genetic testing for Marfan syndrome is single gene DNA sequencing, as the disease is typically a product of a variation in the FBN1 gene. This is the case for up to 90% of the time. If the result of the test is negative, it might be helpful to do the same DNA sequencing for TGFBR1 and TGFBR2. If the aforementioned complications are present and testing is positive for a variation in any of these genes, then it is highly likely that someone has Marfan syndrome [3]. But if there are no symptoms present, then there is a chance that the person has another disease. There is a 50% chance that a parent with the disease will pass it on to their offspring, so it is important to have as many family members as possible test [1].

Scientific Risks of Testing

            Having a genetic variation in the FBN1 gene usually causes some sort of condition that is paired with Marfan syndrome, such as the common variant rs12916536 leading to adolescent scoliosis [4]. However, testing for this gene is not always straightforward. For example, other variations of the gene can be linked to ectopia lentis syndrome, Weill-Marchesani syndrome, Shprintzen-Goldberg syndrome and neonatal progeroid syndrome [5]. Because of that, it is important to test multiple family members if there is a discovered variant in the FBN1 gene. Some of these gene changes could actually be polymorphisms, which are not likely to cause Marfan syndrome [5], so the risk of someone having a variation in the gene to also have Marfan syndrome is not a certainty, but not having that variation does mean that one does not have the disease.

Ethical Considerations

            Most of the ethical questions regarding genetic testing used for Marfan syndrome is meant to question if genetic testing is even the best method to determine if one has Marfan syndrome. First of all, the cost might not be worth it because of the obvious physical characteristics of one with Marfan syndrome. As a child works through adolescence, they eventually would be able to notice their unusually long limbs and fingers and would likely have other abnormalities common for the disease. While that might not be indicative of anything other than just being tall and skinny, there are enough complications with the body caused by Marfan syndrome that would pile up and ultimately cause worry. But even still, they would have to test in some manner to be sure.

Another reason why a DNA sequencing might not be the best option is that there are other tests that one can have, such as an EKG, cardio ultrasound, cardiac MRI, or CT scan. These are the best ways to see abnormalities with the heart, blood vessels, spine, and skeletal system. These tests however are typically more expensive than the genetic test, which is usually around $2,000 [5]. However, being able to see the plethora of complications through these medical examinations seems to be more effective than the genetic test, as variations found in the test might not prove someone has Marfan syndrome. People who take the genetic test would end up having to pay north of $2,000 more for a different test to get complete accuracy.

There also come the behavioral and psychological effects that come with knowing you have Marfan syndrome. Initially, there are feelings of denial, anger, and depression, which come with many diseases. But accepting that you or someone close has the disease means living a different way of life. For example, it is important to stay out of active sports and all activities that put someone at risk for severe injury. Also, people affected must come to terms with the idea that they look different than others and that they would in some cases need special protection. Finding the balance of protecting yourself or your child while still being as involved in activity as possible will alleviate some of the frustration with the way of life [6].

Questions to Ask Before Getting the Test

  • If someone in the family has already tested positive, what are the chances that a child also tests positive? Children have a 50% chance of having the disease if one parent does. For more extended family, the chances vary as different parents come into play.
  • What should be the plan if someone tests positive? The first thing to consider if someone tests positive is whether or not they want to participate in further screenings. If the cost of that isn’t worth it, then someone who tests positive should at least act as though they do have the disease, especially if they possess some of the bodily complications.
  • What types of environmental factors should they consider changing if they test positive? Someone who tests positive should most certainly continue to stay active, but to a much lesser degree. Active sports and heavy lifting are highly dangerous to someone with Marfan syndrome, but it is absurd to completely remove physical activity from someone’s life.

Ultimately, a certain level of concern that you might have Marfan syndrome would make it worth it to get tested in some manner, whether it be genetic testing, medical screening, or both. Knowledge that you might have to change your lifestyle is scary, but it beats the likely alternative of dying from the complications of Marfan syndrome when you weren’t aware you had it.

References

  1. “What Is Marfan Syndrome?” The Marfan Foundation, 3 Oct. 2018, www.marfan.org/about/marfan.
  2. “Marfan Syndrome.” National Center for Biotechnology Information, U.S. National Library of Medicine, www.ncbi.nlm.nih.gov/gtr/conditions/C0024796/.
  3. “Marfan Syndrome – FBN1 Gene.” National Center for Biotechnology Information, U.S. National Library of Medicine, www.ncbi.nlm.nih.gov/gtr/tests/502890/.
  4. Sheng, Fei, et al. “New Evidence Supporting the Role of FBN1 in the Development of Adolescent Idiopathic Scoliosis.” National Center for Biotechnology Information, U.S. National Library of Medicine, 15 Feb. 2019, www.ncbi.nlm.nih.gov/pubmed/30044367.
  5. “Marfan Syndrome Diagnosis and Tests.” Cleveland Clinic, 3 May 2019, my.clevelandclinic.org/health/diseases/17209-marfan-syndrome/diagnosis-and-tests.
  6. Bennett, Robin L., and Meinhard Robinow. “Marfan Syndrome.” University of Washington Orthopedics and Sports Medicine, orthop.washington.edu/patient-care/articles/arthritis/marfan-syndrome.html.
  7. Zink, William P., “Marfan Syndrome.” August 2015, http://zinkmd.com/portfolio/amet-sollicitudin.

Hemochromatosis

By: Silvy Park

What is it?

Hemochromatosis is a disorder in which the body stores too much iron (excess iron is not effectively removed from the blood). This is dangerous because too much iron is toxic and can poison your organs, resulting in severe organ failure and even death. Common symptoms include joint pain, fatigue, general weakness, weight loss, and stomach pain. The prognosis for people who have hemochromatosis depends on how much organ damage they have upon diagnosis. Therefore, early diagnosis is important for treatment. Moreover, Hereditary Hemochromatosis, or HH, is more common in Caucasian men. In fact, some research highlights that men are five times more likely to have it than women. 

The HFE Gene

The HFE gene is responsible for the genetic variation. It makes sense that the variations change the gene expression because the gene encodes for the hemochromatosis protein in humans and regulates iron absorption by regulating the interaction of the transferrin receptor with transferrin.

There are two main alleles in the HFE gene: rs1800562, also known as C282Y (risk genotype AA), which can cause a serious form of Hemochromatosis and rs1799945, also known as H63D (risk genotype GG), which can cause a mild form of Hemochromatosis [4]. 

Besides Type 1 HH, there are also Type 2 and Type 3 hemochromatosis, which are both also recessively inherited. Type 2 hemochromatosis results from mutations in the HJV or HAMP genes, while Type 3 hemochromatosis results from mutations in the TFR2 gene.

Pros and Cons: Why Should You Get Tested? 

Pros: 

  • Hemochromatosis is one of the most common hereditary disorders in the United States, with about 1 in every 8-12 Caucasians in the United States being a carrier (one copy of the HFE defect) and about 5 in every 1,000 to have two copies of the HFE defect [3]. 
  • Genetic testing can show whether you have one or two recessive HFE gene(s). 
  • You can be prepared. Symptoms of hemochromatosis usually appear in men between the ages of 30 and 50. Symptoms often do not appear in women until after age 50 or after menopause, most likely because women lose iron from the blood loss of menstruation and childbirth.
  • Getting a test done can help a person avoid serious symptoms of the disorder. If left untreated, the disorder can lead to cirrhosis of the liver, diabetes, hypermelanotic pigmentation of the skin, heart disease, liver cancer, depression, and fatigue, all of which can be easily avoided if a person is treated beforehand [4].
  • HH is a candidate for genetic screening because the mutations associated with HH are present at birth, even though symptoms do not show up until adulthood. 
  • If people who have hemochromatosis want offspring, genetic testing and counseling can determine the likelihood of the parents passing the HH genes on to their children.

Cons:

  • Having two copies of the Hereditary Hemochromatosis alleles will not necessarily cause the disorder.
  • Tests cannot predict whether you’ll develop signs and symptoms of hemochromatosis. Therefore, there is no strong evidence supporting a connection between these variations and the trait in questions [1]. 
  • The test is relatively expensive, considering that the odds of actually having Hereditary Hemochromatosis and its extreme symptoms are very unlikely.

Testing

A recommended test for hemochromatosis is an iron panel of blood tests. A complete iron panel typically includes the following: Ferritin, Transferrin Saturation %, Serum Iron, and TIBC/UIBC [5]. DNA genetic testing can be done by collecting calls from the inside of your mouth using a cotton swab or drawing blood from an arm vein [3]. Cost is usually around $100 to analyze the HFE gene. A comprehensive genetic test that analyzes five genes associated with HH is shown below. Cost varies but is usually less than $100.

Q & A:

If someone in the family has already tested positive, what are the chances that a child, nephew, aunt will test positive?

Most people who have HH inherit two hemochromatosis genes, one from each parent. Having a person in your family with HH does increase your chance of having HH as well, but not everyone who inherits the genes develops symptoms or complications of the disease. 

What should be your plan if you test positive or negative? 

HH can be easily treated by phlebotomy or regular donation of blood to reduce blood iron levels. Iron chelation therapy uses medicine to remove excess iron from your body. However, those with two copies of Hereditary Hemochromatosis who are diagnosed as not having Hemochromatosis should still familiarize themselves with the symptoms in case it develops later.

What type of screening is recommend if you do test positive?

If you test positive for the HFE gene mutation, it is recommended that you test for Hemochromatosis through an iron panel of blood tests.

What type of environmental factors should you consider changing in response to a positive test?

Keeping a low-iron diet can help a lot. For example, avoid taking iron pills and limit the intake of Vitamin C.

References

[1] Adams, P. C. (2002). Screening for Hemochromatosis. BC Medical Journal, 44. Retrieved from https://www.bcmj.org/articles/screening-hemochromatosis—should-we-do-last-test-first

[2] Chandrasekharan, S., Pitlick, E., Heaney, C., & Cook-Deegan, R. (2010). Impact of gene patents and licensing practices on access to genetic testing for hereditary hemochromatosis. Genetics in Medicine, 12. doi: 10.1097/gim.0b013e3181d7acb0

[3] Hemochromatosis. (n.d.). Retrieved from https://www.nhlbi.nih.gov/health-topics/hemochromatosis.

[4] Hemochromatosis. (2018, May 21). Retrieved from https://www.snpedia.com/index.php/Hemochromatosis.

[5] Lewis, E. (2019, July 25). Hemochromatosis Lab Testing. Retrieved from https://hemochromatosishelp.com/hemochromatosis-testing/.

Childhood Asthma- Will O’Neil

The rs7216389 SNP is associated with susceptibility to Childhood Asthma. Childhood Asthma is when a child’s lungs and airways become easily inflamed when they are exposed to certain triggers, such as exposure to pollen or respiratory infections. Symptoms of asthma include “shortness of breath, chest tightness or pain, trouble sleeping caused by shortness of breath, coughing or wheezing, whistling or wheezing sound when exhaling (wheezing is a common sign of asthma in children), or coughing or wheezing attacks that are worsened by a respiratory virus, such as a cold or the flu.” (Mayo Clinic) The genotype CC gives the patient 0.69x lower risk of Childhood Asthma. The genotype CT gives the patient a normal risk for Childhood Asthma. The genotype TT gives the patient a 1.5x increased risk for Childhood Asthma. Asthma is the most chronic condition among children, affecting about 6.1 million kids under the age of 18. The protein IL-13 (interleukin-13) causes changes in the airways of asthma patients. It is a naturally occurring protein made by the IL13 gene, and it leads to inflammation, which in this case would be the lungs and airways. It does not alter any traits.

Any child should be tested for asthma, but children of parents who have asthma are more at risk and should be tested for rs7216389. If they have this, they will be more at risk to develop childhood asthma. To test this, I would recommend Single Gene DNA sequencing which should only cost around $10. The normal trait in question would be a CT genotype while a higher risk of the disease would be a TT genotype, and a lower than normal risk would be a CC genotype. There is evidence supporting the variations and the risk of Childhood Asthma two studies that both showed a correlation between the TT genotype and a higher risk of developing Childhood Asthma. Everyone has a risk of developing asthma based on environmental factors. About 1 in every 12 children develops asthma. However, having the TT genotype for the SNP rs7216389 gives children a larger risk for developing Asthma, which is shown through more kids with the TT genotype developing asthma than the other genotypes.

There is not much risk to having the single gene DNA sequencing test done. However, someone may not want to get the test done since it only finds whether you are more at risk to develop childhood asthma. Even if someone tests positive for the TT genotype, they may still never develop childhood asthma. Also, it is not 100% proven yet that the TT genotype with the rs7216389 SNP actually leads to a higher risk of Childhood Asthma.

There are no genetic privacy concerns that the consumer may want to consider. A potential downside of being tested is that even if you test negative, you can still develop Childhood Asthma. There are no studies that look at reactions to testing positive in this case.

If a family member tests positive for this, the child has a higher chance for testing positive. If a child tests positive for this, their plan should be to look out for symptoms of Asthma to be on top of it in case of an onset of severe Asthma. If someone tests positive for this, I would recommend telling your doctor that you tested positive for a gene that leads to a higher risk of developing Asthma. Then, the doctor may want to test for asthma in the patient. If someone does test positive for asthma, they should reduce the time that they spend doing the things that lead to their asthma symptoms, such as exercise, but not necessarily eliminate it from their daily lives. When doing these things, such as exercising, they need to watch for changes in breathing and for wheezing to prevent an asthma attack from happening before it actually happens.

Words Cited

Centers for Disease Control and Prevention. (2019, October 19). Asthma. Retrieved from https://www.cdc.gov/asthma/default.htm.

Mayo Clinic. (2018, June 4). Asthma. Retrieved from https://www.mayoclinic.org/diseases-conditions/asthma/symptoms-causes/syc-20369653.

Science Daily. (2011, March 22). Protein associated with allergic response causes airway changes in asthma patients. Retrieved from https://www.sciencedaily.com/releases/2011/03/110322151256.htm#:~:targetText=Summary%3A,according%20to%20a%20new%20study. 

SNPedia. (2019, July 3). rs7216389. Retrieved from https://www.snpedia.com/index.php/Rs7216389.

Alcoholism Blog

What is alcoholism?

The definition of alcoholism is “an addiction to the consumption of alcoholic liquor or the mental illness and compulsive behavior resulting from alcohol dependency” (google). This “dependency” on alcohol increases health risks greatly in comparison to those who are not dependent on alcohol. The National Institute of Health (NIH) shares statistics saying 5.7% of people 18 and older have AUD (alcohol use disorder), while 1.8% of children 12-17 have AUD. NIH also shares the risks of alcohol disorders: liver failure, strokes, cardiomyopathy, and much more.

According to SNPedia, there are 6 main genes & 7 SNPs that impact likelihood of alcohol dependency. The six genes include: GHS-R1A, GABRA 2, SLC6A4, OPRM1, D2, and SLC6A3. Many of these genes are genes expressed in the brain, opioid receptor, dopamine receptor, dopamine transporter gene, neurotransmitter transporter. This is part of the reason alcoholism is a very dangerous disease and hard to overcome.

Testing for Alcoholism

There are many reasons people would want to get tested for increased alcoholism related traits. SNPs such as rs27048 and rs27072 are associated with very dangerous symptoms, such as seizures. For these two SNPs, I would recommend a SNP test, which would cost around $200. If one wants to see if they simply have increased chances for alcoholism, they would need a whole genome sequence testing, which costs hundreds of dollars. If one wants one specific test for the most common allele, they can also do that by single-gene testing. Personally, I would only recommend using whole genome sequencing if you have increased likelihood of severe symptoms or if alcoholism runs in your family. Ultimately, there is a strong correlation between alcoholism and genetics.

Downsides of Testing

Taking a whole genome sequencing test can inform one of many different variations within all of their genes. This can potentially lead them to variations in alleles they didn’t affect that increase risks for other diseases. Limitations for this test are that not all variations of the alleles increase the risk by a substantial amount; therefore, there is a possibility $1000+ may allow you to find something out that does not matter too much.  There are a few disadvantages of this test. First, the role of most of the genes in the human genome is still unknown or incompletely understood. Therefore, a lot of the “information” found in a human genome sequence is unusable at present. Also, an individual’s genome may contain information that they do not want to know. For example, a patient could undergo genome sequencing in order to determine the most effective treatment plan for high cholesterol. In the process, researchers could potentially find an allele that relates to a terminal illness with no effective treatment.

Ethical Concerns

Considering how vast the information in a whole genome sequence test is, it is dangerous if this information is released, and since these tests are newer, security measures to protect this information is still new. Thus, increasing the likelihood of personal information being released. Also, people often find out about diseases they have that they did not expect. This can cause people to become shocked and/or depressed.

  1. Facts about Alcoholism & Precautions to Take
    1. FACT: It is less than 50% likely for a child to develop alcoholism if their parent had it.
    1. FACT: Alcoholism is roughly half genetics and half hereditary.
    1. PRECAUTION: Become more cautious if you have the SNP that increases likely hood of alcoholism. Be aware when drinking or take measures if already an alcoholic.
    1. PRECUATION: If one is being cautious their self, they do not necessarily need to inform doctors, but rather family. However, if it is getting out of hand, they need to go to rehab and should immediately consult a doctor.
    1. PRECAUTION: No screenings necessary unless excessive binge drinking has occurred… should check liver and other body parts to ensure there is not any organ failure.

Works Cited

“Alcohol Facts and Statistics.” National Institute on Alcohol Abuse and Alcoholism, U.S. Department of Health and Human Services, 20 Nov. 2019, www.niaaa.nih.gov/publications/brochures-and-fact-sheets/alcohol-facts-and-statistics.

“Alcoholism.” SNPedia, www.snpedia.com/index.php/Alcoholism.

Christensen, Kurt D, and Robert C Green. “How Could Disclosing Incidental Information from Whole-Genome Sequencing Affect Patient Behavior?” Personalized Medicine, U.S. National Library of Medicine, June 2013, www.ncbi.nlm.nih.gov/pmc/articles/PMC3852635/.

Crane, Marisa. “Is Alcoholism Hereditary or Genetic?” American Addiction Centers, americanaddictioncenters.org/alcoholism-treatment/symptoms-and-signs/hereditary-or-genetic.

“Whole Genome Sequencing.” Genetics Generation, knowgenetics.org/whole-genome-sequencing/.

Huntington’s Disease

Genomes Blog Post

By: Emily Larking

Huntington’s Disease is an inherited neurological illness. About 30,00 people in the United States have the disease (1). It is caused by a mutation on the HD gene, that codes for huntingtin protein production which has much more repeats than normal of a certain three-basese sequence (1). This gene is located on the fourth chromosome. It causes the degeneration of nerve cells in the brain that leads to symptoms such as changes in behavior and judgement, uncontrollable movement and physical changes such as impaired ability to swallow or speak (3).

For a predictive genetic test, the price is $200-$300. There is recommended genetic counseling that can cost up to $1,500-$2,000 (4).  The most effective test is a direct-to-consumer genetic test that counts the extra repeats of the three base sequence in the Huntington gene on the fourth chromosome through a blood sample (3). The test could use a method such as the Southern Blot method. There is a very strong, almost definitive connection between the mutation in the fourth chromosome that would be tested for, and the disease.

With the direct genetic test, there is a small amount of people who have a borderline amount of repeats. Their family may be called in for genetic testing as well to get a better picture. Huntington’s can be ruled out if there are 26 or fewer repeats (3). The test can’t predict when the symptoms will start or the course of the disease (2).

There are many potential implications if the genetic testing is positive for Huntington’s Disease. There may be personal stress and possible distress to those close to the person with Huntington’s Disease. Also, Huntington’s does not have a cure. Therefore, there is no medical advantage to knowing the test results. You can only treat the symptoms as they appear. You can, however, plan for the future and factor that into any family planning decisions. The Genetic Information Non Discrimination Act (GINA) is a law that was made to stop discrimination from based on genetic information with health insurance. Although it applies to health insurance, it does not apply to life insurance so a positive test may raise prices for life insurance dramatically or may not allow for getting a policy at all. (2)

Since Huntington’s is an autosomal dominant disease, the chances of getting it if even one parent has HD will be fairly high. If both the parents have recessive alleles, the offspring will not get the disease. However, if you have two heterozygous, there’s a 75% chance of getting the disease. If one parent is heterozygous and one homozygous recessive, there’s a 50% chance. If one parent is heterozygous and one homozygous dominant, there’s a 100% chance of getting the disease. If the test is positive, the person should make a plan for the future and be prepared to address the symptoms as they come. I would recommend telling the doctor that the test was positive and ask if they have any suggestions on how to proceed.

Overall, Huntington’s Disease is an incurable disease with limited reasons to test for it. Since it is a dominant disease, there is a small chance of one developing it if it does not run through the family. Although not too complicated to test for, the consequences of a positive result outweigh the benefits in most cases.

Works Cited:

About Huntington’s Disease. (2011, November 17). Retrieved from 

https://www.genome.gov/Genetic-Disorders/Huntingtons-Disease. (1)

Genetic testing and your rights. (n.d.). Retrieved from 

https://hdsa.org/find-help/healthcare-and-future-planning/genetic-testing-and-your-rights/ . (2)

Huntington’s Disease: Hope Through Research. (2019, August 13). Retrieved from 

https://www.ninds.nih.gov/disorders/patient-caregiver-education/hope-through-research/h

untingtons-disease-hope-through#7. (3)

Goodman, L. V. (2013, January 29). Predictive Testing for Huntington’s disease. Retrieved from

 http://hddrugworks.org/dr-goodmans-blog/predictive-testing-for-huntingtons-disea. (4)