Winning Submissions 2025

Symphony of Our Genes: A Journey into Genetic Diversity and Human Health

Mei Bejdo Gjimnazi Sami Frasheri, Tirane, Albania

Beneath our skin, beyond the mirror of our eyes, lies a hidden language—one not spoken, but written in four letters: A, T, C, and G. These letters, strung together in intricate sequences, compose the 20,000-or-so genes that orchestrate the very essence of who we are. But no two symphonies are alike. Just as each snowflake spirals uniquely from the clouds, each human genome holds subtle variations—some barely whispering their presence, others shouting across generations. This invisible mosaic of genetic diversity is not just a marvel of nature, but the compass guiding modern medicine. To understand this diversity is to understand why one person succumbs to disease while another resists, why a drug heals one and harms another. In a world racing toward personalized healthcare, genetic diversity is the map—and ignorance of it is a risk we can no longer afford.

Imagine two hearts, both beating in rhythm, yet one falters after surgery despite standard treatment. The culprit? A single gene named CYP2C19, a quiet engineer of metabolism. For many, this gene processes clopidogrel, a blood-thinner essential for preventing clots. But for others—those carrying the CYP2C19 *2 or *3 variants—this gene malfunctions, leaving the medication inert. The result? A heart unprotected, a life endangered. In such moments, the beauty of genetic testing unfolds—not as a distant promise, but as an urgent necessity. This is the frontier where knowledge of DNA saves lives. Doctors informed of a patient’s genotype can pivot to safer, more effective treatments, bypassing the peril of a one-size-fits-all prescription. It is here, in these precise pivots, that genetic diversity transforms from abstract data into lifesaving action.

But genes do more than shape our response to drugs—they inscribe the stories of our vulnerabilities and strengths. Enter BRCA1 and BRCA2, names etched in medical history. Variants in these genes, found disproportionately in some populations, drastically elevate the risk of breast and ovarian cancers. Yet, knowledge is power. Women who discover these mutations through genetic screening are no longer bound to fate; they’re armed with options—from enhanced monitoring to preventative surgery. In such cases, understanding genetic diversity becomes a shield, crafted not of metal, but of molecular foresight. It empowers individuals to rewrite their destinies before illness writes them instead.

Zooming out from individual genes, genetic diversity also offers a lens into population-level resilience and risk. The HBB gene, mutated in sickle cell disease, is one such paradox. Carriers of the sickle trait, predominantly from African and Mediterranean ancestry, inherit a defense against malaria—a deadly foe in their ancestral lands. Yet this evolutionary shield comes with cost: a risk of sickle cell complications. This genetic give-and-take reminds us that diversity is not just biological but historical, woven through centuries of migration, adaptation, and survival. Any health system blind to such context is doomed to misdiagnose, mistreat, and misunderstand the very people it seeks to heal.

As we peer into the genome’s glowing code with the tools of modern science, one truth becomes clear: understanding genetic diversity is not optional; it is foundational. It is the path to equitable medicine, to a future where treatment is tailored not by guesswork, but by genetic insight. Initiatives like the 1000 Genomes Project and the European Society of Human Genetics’ outreach through EuroGEMS are already lighting this path. But we must walk it faster. We must fund research, educate clinicians, and engage communities. Only then can we transform our collective genetic symphony—from a scattered hum into a chorus of healing.

References: Scott, S. A., et al. (2013). Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C19 and Clopidogrel Therapy. Clinical Pharmacology & Therapeutics. Mavaddat, N., et al. (2013). Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers. Cancer Epidemiology, Biomarkers & Prevention Tishkoff, S. A., et al. (2001). Haplotype diversity and linkage disequilibrium at human G6PD: Recent origin of alleles that confer malarial resistance. Science.

Genetic Diversity : The Depth of One Percent

Minseo Kim Carmel High School, United States

More than 99% of the human genome is shared, meaning that only around 1% or less of your genetic material is what makes you different from other people[1]. Despite such a quite literal molecular difference, that genetic variety is what makes the human system and healthcare so difficult to generalize. Difference in genetic makeup creates different responses to medicine, different metabolic characteristics, and even different makeup of common diseases in a population. Throughout history, the importance of genetic diversity had been underestimated and clinical studies were often inaccessible or disregarding social minority populations. Such negligence and the lack of data led to severe progression of disease and even fatal results. In the present, scientists and healthcare workers are studying and archiving a variety of genes to better understand the diverse expression of the human body and to create management and prevention standards that can help reduce risks and healthcare costs for many. However, some populations still remain underrepresented, signifying that the science community still has to work towards the formation of a more diverse and inclusive research environment. Genetic difference calls for different medical procedures and medicine dosages. A 2006 study reports that individuals with variants of the RYR1 gene have a greater risk of Malignant Hyperthermia, a condition where certain volatile anesthetics can cause fatal symptoms such as fever, abnormal muscle contraction, and tachycardia[2]. Patients with this genetic variant could suffer critical harm if they or their healthcare organizations were not knowledgeable of their condition. The dosage and efficacy of medical drugs is also different among individuals with different genetic makeup. CYP2C19 is a liver enzyme that catalyzes the breakdown and metabolism of drugs. Variants in this gene result in different manner, efficiency, and rate of drug absorption[3]. A 2019 study on Clopidogrel, an antiplatelet medication, reports that individuals with two copies of non-functional alleles of CYP2C19 have reduced activation rate of Clopidogrel, resulting in a higher chance of cardiovascular event compared to other patients with functional alleles[4]. A one-fits-all medical standard would put patients at constant risk of being poorly treated with widely generalized medications that have little or adverse effect to them. Being familiar and well-informed of genetic variants is crucial to long-term management of diseases as well. Sickle Cell Disease is an inherited disease that causes red blood cells to polymerize into crescent shapes under oxidative stress due to a point mutation in the HBB gene[5]. Patients of Sickle Cell Disease experience medical crises under situations demanding high respiration and metabolism. When the doctor provides their patient with health instructions, being aware of underlying genetic complications like Sickle Cell Disease that could impact the feasibility of a health plan can help the patient receive an effective, actionable goal that does not contradict their genetic disease management. Acknowledging and studying diverse genetic variants and their impact on human health can make the healthcare system trustable and accessible for more people with diverse conditions. Despite the importance of genetic diversity in healthcare, many variants of genes and the corresponding population still remain underexplored. Although decreasing in number, some studies continue to resort to an overrepresented study sample, giving hastily generalized conclusions that are inapplicable to a number of real-life patients. The fact that DNA is a highly personal component also contributes to the difficulty of trying to reflect real-life genetic diversity to the research environment; genetic material cannot be regularly taken in great amounts in numerous communities at random. Therefore, individual interest in one’s own genetic makeup and the willingness to scientifically confirm it is the most important factor for the science community to achieve high resemblance to the actual population in their experiment. To encourage research participation of underrepresented populations, the role genetics play in the shaping of human health should be taken seriously in healthcare services and widely educated to the public.

References: [1] Collins, Francis S., and Monique K. Mansoura. “The Human Genome Project.” Cancer, vol. 91, no. S1, 1 Jan. 2001, pp. 221-225, https://doi.org/10.1002/1097-0142(20010101)91:1+<221::aid-cncr8>3.0.co;2-9. [2] Robinson, Rachel, et al. “Mutations in RYR1 in malignant hyperthermia and central core disease.” Human Mutation, vol. 27, no. 10, Oct. 2006, pp. 977-989, https://doi.org/10.1002/humu.20356. [3] Qamar Shubbar, Aminah Alchakee, Khaled Walid Issa, Abdul Jabbar Adi, Ali Ibrahim Shorbagi, & Maha Saber-Ayad. (2024). From genes to drugs: CYP2C19 and pharmacogenetics in clinical practice. Frontiers in Pharmacology, 15. https://doi.org/10.3389/fphar.2024.1326776 [4] Pereira, N. L., Rihal, C. S., So, D. Y. F., Rosenberg, Y., Lennon, R. J., Mathew, V., Goodman, S. G., Weinshilboum, R. M., Wang, L., Baudhuin, L. M., Lerman, A., Hasan, A., Iturriaga, E., Fu, Y.-P., Geller, N., Bailey, K., & Farkouh, M. E. (2019). Clopidogrel Pharmacogenetics. Circulation: Cardiovascular Interventions, 12(4). https://doi.org/10.1161/circinterventions.119.007811 [5] Elendu, C., Amaechi, D. C., Alakwe-Ojimba, C. E., Elendu, T. C., Elendu, R. C., Ayabazu, C. P., Aina, T. O., Aborisade, O. B., & Adenikinju, J. S. (2023). Understanding Sickle Cell disease: Causes, symptoms, and Treatment Options. Medicine, 102(38), e35237-e35237. https://doi.org/10.1097/md.0000000000035237

Every Genome Counts

Arwen Shah Greenwood High, Babgalore, India

Prescribing the same drug dosage to a Norwegian farmer, a Maasai pastoralist, and a Japanese office worker would defy both logic and biology—yet this is precisely the blind spot created by Eurocentric genomic research. The human genome varies more across populations than traditional medical studies acknowledge, with consequences ranging from ineffective treatments to undiagnosed diseases. While isolated populations like the Finns and Ashkenazi Jews have provided crucial insights through ‘founder effects’ [1], their genetic homogeneity cannot represent humanity’s complexity. Modern biobanks, though revolutionary, replicate this bias: the UK Biobank’s dataset is 94% European, and GWAS studies overrepresent Europeans by 80%. This exclusion has tangible costs[2]. Consider APOL1, where G1 and G2 variants—selected in West Africans for resistance to trypanosomiasis—increase kidney disease risk [3]. These alleles went unnoticed for decades because early renal studies focused on Europeans, delaying critical screening protocols for millions of African-descended patients. Pharmacogenomics reveals even starker disparities. Warfarin, a blood thinner, requires precise dosing guided by VKORC1 and CYP2C9 variants. Europeans with the VKORC1 rs9923231-T allele metabolize the drug slowly, needing lower doses, while many Africans lack this variant and require higher doses [4]. Early guidelines based on European data led to dangerous overdoses in African patients, increasing hemorrhage risk. Similarly, the antiplatelet drug clopidogrel depends on CYP2C19 for activation. East Asians frequently carry loss-of-function alleles (CYP2C19*2/*3), rendering the drug ineffective and elevating stroke risk—a problem overlooked until population-specific studies revealed it [5]. The painkiller codeine’s metabolism tells a parallel story: ultra-rapid CYP2D6 metabolizers, common in Ethiopia, convert codeine to morphine too efficiently, risking fatal overdose in infants through breast milk [6], while slow metabolizers in East Asia may get no pain relief at all. These examples underscore that precision medicine cannot be “precise” without diverse data. Disease susceptibility also follows population-specific patterns. The SLC16A11 variant, present in 50% of Native American-derived groups but rare in others, increases type 2 diabetes risk by disrupting lipid metabolism—a discovery made only when researchers included Mexican participants [7]. Similarly, PCSK9 variants like Y142X in African Americans and R46L in Europeans lower LDL cholesterol and reduce heart attack risk by up to 88%, inspiring blockbuster PCSK9 inhibitor drugs [8]. Yet these breakthroughs nearly missed populations excluded from early studies. Even protective mutations reflect evolutionary trade-offs: the CCR5-Δ32 deletion, found in 10% of Europeans, confers HIV resistance but increases West Nile virus susceptibility [9], while APOL1’s kidney risks accompany its parasite defense. Such nuances vanish when research ignores diversity. Convergent evolution further complicates the picture. Lactose tolerance, often mislabeled a “European” trait, arose independently in African pastoralists (via the -14010C mutation), Middle Easterners (-13915T), and Northern Europeans (-13910T) [10]. Each population evolved lactase persistence through distinct genetic pathways—a fact obscured when studies focus on one group. Similarly, sickle cell mutations protect against malaria not only in Africans but also in Greeks and Indians, yet Eurocentric narratives historically framed it as an “African disease” [11]. These oversimplifications hinder both scientific understanding and clinical care. The ethical and practical consequences are profound. Transthyretin (TTR) amyloidosis, a deadly cardiac condition, was misclassified as “rare” in Africans until H3Africa research identified it as a major cause of heart failure in Ghana and Kenya [12]. Similarly, 275 million genetic variants in the NIH’s All of Us Program—which prioritizes diversity—were absent from prior databases [13]. Without such inclusion, precision medicine risks exacerbating disparities: polygenic risk scores for breast cancer, developed using European data, fail to predict risk accurately in African American women, delaying lifesaving screenings. Initiatives like H3Africa and All of Us are correcting these gaps, but systemic change requires deeper shifts. Embedding pharmacogenomic testing into routine care, as Mayo Clinic’s RIGHT Study did for CYP2C19 and CYP2D6 [14], could prevent thousands of adverse drug reactions. Global biobanks, from Qatar Genome to Singapore’s SG10K, must become the norm, not exceptions. Most critically, research must shift from extracting data from marginalized populations to empowering them as partners—a lesson learned from the exploitation of the Havasupai Tribe’s DNA in the early 2000s [15]. The future of medicine belongs not to the best-studied populations, but to the best science—and that science must include us all.

References: 1. Solaimani, E. (2024, September 12). History Shapes Genes: The Impact of the Founder Effect on Jewish Populations. Jnetics. https://www.jnetics.org/the-founder-effect/ 2. Carress, H., Lawson, D. J., & Elhaik, E. (2021). Population genetic considerations for using biobanks as international resources in the pandemic era and beyond. BMC Genomics, 22(1), 351. https://doi.org/10.1186/s12864-021-07618-x 3. Pollak, M. R., & Friedman, D. J. (2023). APOL1 and APOL1-associated kidney disease: A common disease, an unusual disease gene—Proceedings of the Henry Shavelle Professorship. Glomerular Diseases, 3(1), 75-87. https://doi.org/10.1159/000529227 4. Limdi, N. A., Arnett, D. K., Goldstein, J. A., Beasley, T. M., McGwin, G., Adler, B. K., & Acton, R. T. (2008). Influence of CYP2C9 and VKORC1 on warfarin dose, anticoagulation attainment and maintenance among European-Americans and African-Americans. Pharmacogenomics, 9(5), 511-526. https://doi.org/10.2217/14622416.9.5.511 5. Dean, L., & Kane, M. (2012, March 8). Clopidogrel therapy and CYP2C19 genotype. In V. M. Pratt, S. A. Scott, M. Pirmohamed, et al. (Eds.), Medical Genetics Summaries. National Center for Biotechnology Information (US). https://www.ncbi.nlm.nih.gov/books/NBK84114/ 6. Dean, L., & Kane, M. (2012, September 20). Codeine therapy and CYP2D6 genotype. In V. M. Pratt, S. A. Scott, M. Pirmohamed, et al. (Eds.), Medical Genetics Summaries. National Center for Biotechnology Information (US). https://www.ncbi.nlm.nih.gov/books/NBK100662/ 7. González, M. J., Reyes, M., & Lera, L. (2021). Genetic variants in the SLC16A11 gene are associated with increased BMI and insulin levels in nondiabetic Chilean population. Archives of Endocrinology and Metabolism, 65(3), 351-358. https://doi.org/10.20945/2359-3997000000359 8. Guella, I., Asselta, R., Ardissino, D., Merlini, P. A., Peyvandi, F., Kathiresan, S., Mannucci, P. M., Tubaro, M., & Duga, S. (2010). Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population. Journal of Lipid Research, 51(11), 3342-3349. https://doi.org/10.1194/jlr.M010009 9. Dinh, K. M., Kaspersen, K. A., Mikkelsen, S., Kjerulff, B. D., Boldsen, J. K., Petersen, M. S., Burgdorf, K. S., Sørensen, E., Aagaard, B., Forman-Ankjær, B., Bruun, M. T., Banasik, K., Hansen, T. F., Nyegaard, M., Rohde, P. D., Brunak, S., Hjalgrim, H., Ostrowski, S. R., Pedersen, O. B., Ullum, H., Erikstrup, L. T., & Erikstrup, C. (2024). Impact of CCR5Δ32 on the risk of infection, Staphylococcus aureus carriage, and plasma concentrations of chemokines in Danish blood donors. eBioMedicine, 109, 105406. https://doi.org/10.1016/j.ebiom.2024.105406 10. Inlamea, O. F., Soares, P., Ikuta, C. Y., Heinemann, M. B., Achá, S. J., Machado, A., Ferreira Neto, J. S., Correia-Neves, M., & Rito, T. (2020). Evolutionary analysis of Mycobacterium bovis genotypes across Africa suggests co-evolution with livestock and humans. PLOS Neglected Tropical Diseases, 14(3), e0008081. https://doi.org/10.1371/journal.pntd.0008081 11. Mohammed, A. O., Attalla, B., Bashir, F. M., Ahmed, F. E., El Hassan, A. M., Ibnauf, G., Jiang, W., Cavalli-Sforza, L. L., Karrar, Z. A., & Ibrahim, M. E. (2006). Relationship of the sickle cell gene to the ethnic and geographic groups populating the Sudan. Community Genetics, 9(2), 113-120. https://doi.org/10.1159/000091489 12. Damrauer, S. M., Chaudhary, K., Cho, J. H., Liang, L. W., Argulian, E., Chan, L., Dobbyn, A., Guerraty, M. A., Judy, R., Kay, J., Kember, R. L., Levin, M. G., Saha, A., Van Vleck, T., Verma, S. S., Weaver, J., Abul-Husn, N. S., Baras, A., Chirinos, J. A., Drachman, B., Kenny, E. E., Loos, R. J. F., Narula, J., Overton, J., Reid, J., Ritchie, M. D., Sirugo, G., Nadkarni, G., Rader, D. J., & Do, R. (2019). Association of the V122I hereditary transthyretin amyloidosis genetic variant with heart failure among individuals of African or Hispanic/Latino ancestry. JAMA, 322(22), 2191-2202. https://doi.org/10.1001/jama.2019.17935 13. All of Us Research Program. (2024, February 19). 275 million new genetic variants identified in NIH precision medicine data. National Institutes of Health. https://www.nih.gov/news-events/news-releases/275-million-new-genetic-variants-identified-nih-precision-medicine-data 14. Wang, L., Scherer, S. E., Bielinski, S. J., Muzny, D. M., Jones, L. A., Black, J. L., … Weinshilboum, R. M. (2022). Implementation of preemptive DNA sequence-based pharmacogenomics testing across a large academic medical center: The Mayo-Baylor RIGHT 10K Study. Genetics in Medicine, 24(5), 1062-1072. https://doi.org/10.1016/j.gim.2022.01.022 15. Kabata, F. (2024). Indigenous Peoples’ human genomic sovereignty: Lessons for Africa. Developing World Bioethics. https://doi.org/10.1111/dewb.12466

Genetic Diversity: A Key Role in Global Health Access and the Fight Against Disease

YİĞİT JENAR YEŞİLYURT ODTÜ GELISTIRME VAKFI ÖZEL KAYSERI ANADOLU LISESI, Kocasinan, Turkey

Over the past century, numerous studies have helped humanity understand how and why genetic diversity arises. The foundations of genetics were laid by James Watson and Francis Crick, the behaviors of genetic diversity were explored by Barbara McClintock, and perhaps most relevant to this essay, the CRISPR-Cas9 technology was developed by Jennifer Doudna and Emmanuelle Charpentier. These scientific milestones have significantly contributed to our current understanding of genetics. Throughout the history of genetic research, it has been observed that certain ethnic groups and animal species possess natural resistance to specific diseases. For instance, people of Viking ancestry from Northern Europe are believed to have a natural immunity to HIV due to a mutation in the CCR5 gene (Δ32), which prevents the virus from entering cells. Such examples are not limited to humans; they are also observed in other animals. Elephants, which have more cells and therefore a theoretically higher risk of cancer, carry twenty copies of the TP53 gene, while humans have only one. This gene acts as a tumor suppressor by triggering the death of cells with high DNA damage. These cases underline the critical importance of genetic diversity in disease resistance. Genetic diversity also explains why individuals respond differently to various diseases. For example, mutations in the BRCA1 and BRCA2 genes significantly increase the risk of breast and ovarian cancer, particularly in women of Western European descent. However, these genetic variants do not occur at the same frequency in all ethnic groups, making it essential to consider diversity when designing universal genetic screening programs. Ignoring such differences may lead to overlooking vital risks in underrepresented communities. Sickle cell anemia is another example tied to genetic diversity. This disease results from a mutation in the HBB gene and is more common among individuals of African descent. The high frequency of this mutation in malaria-endemic regions illustrates an evolutionary advantage—individuals with one copy of the allele are more resistant to malaria. However, individuals with two copies face severe health consequences. This example demonstrates how genetic diversity influences not only disease susceptibility but also adaptation to environmental pressures. Tay-Sachs disease provides a further case. Caused by mutations in the HEXA gene, this fatal neurodegenerative disorder is notably prevalent among genetically isolated populations. Such examples emphasize the necessity for community-specific genetic screening programs to detect and manage hereditary conditions effectively. Moreover, the majority of today’s pharmaceutical drugs are developed based on clinical trials involving populations with relatively homogeneous genetic backgrounds, often of European ancestry. As a result, individuals with different genetic makeups may experience unexpected side effects or fail to respond to treatments. Variations in the CYP450 gene family, which influences how the liver metabolizes drugs, underscore this problem. Genetic differences in these enzymes necessitate personalized dosing and have become a cornerstone of the emerging field of personalized medicine. Despite the growing awareness of this issue, large-scale biobanks such as the UK Biobank, Estonian Biobank, and FinnGen still disproportionately represent European populations. This imbalance highlights a significant gap in the genetic data of people from Africa, Asia, and South America. Such underrepresentation risks perpetuating global health inequalities and limits our understanding of disease susceptibility in diverse communities. Thus, the establishment of more inclusive and equitable genetic databases is both a scientific and ethical imperative. In conclusion, genetic diversity plays a crucial role in shaping both health and disease outcomes. Focusing genomic research solely on specific populations can compromise scientific accuracy and social justice. The future of genetics lies in comprehensive and inclusive studies that reflect the full spectrum of human genetic variation. Only through this approach can we develop truly effective treatments and ensure personalized, equitable healthcare for all.

References: • McClintock, B. (1950). The origin and behavior of mutable loci in maize. PNAS, 36(6), 344-355. https://doi.org/10.1073/pnas.36.6.344 • Doudna, J. A., & Charpentier, E. (2014). The new frontier of genome engineering with CRISPR-Cas9. Science, 346(6213), 1258096. https://doi.org/10.1126/science.1258096 • Hütter, G., et al. (2009). Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. NEJM, 360, 692-698. https://doi.org/10.1056/NEJMoa0802905 • Abegglen, L. M., et al. (2015). Potential Mechanisms for Cancer Resistance in Elephants. JAMA, 314(17), 1850-1860. https://doi.org/10.1001/jama.2015.13134 • Piel, F. B., et al. (2010). Global distribution of the sickle cell gene. Nat Comm, 1, 104. https://doi.org/10.1038/ncomms1104 • Sirugo, G., Williams, S. M., & Tishkoff, S. A. (2019). The Missing Diversity in Human Genetic Studies. Cell, 177(1), 26-31. https://doi.org/10.1016/j.cell.2019.02.048