🎙️ Episode Title: Equity in Focus: Building a Truly Global Genomic Landscape

🧬 In this episode of Base by Base, we address one of the most pressing issues in human genomics: the need to close the ancestral data gap. Published in Cell Genomics, this commentary by Ana Luiza Arruda, Andrew Morris, and Eleftheria Zeggini calls attention to how genomic medicine remains disproportionately centered on individuals of European ancestry—jeopardizing its promise of precision health for all.

The authors highlight why expanding tissue-specific, multi-ancestry molecular datasets is critical for moving genomics forward—from discovery to clinical translation—while promoting equity and inclusion in healthcare innovation.

🔍 Key insights include:

• Systemic underrepresentation: Despite global diversity, most GWAS and molecular QTL data derive from European populations—leaving African, Indigenous, South Asian, and Latin American ancestries critically underrepresented.

• Biological impact: Genetic variants specific to diverse populations often remain undiscovered or uninterpretable due to lack of relevant tissue-specific molecular data, such as gene expression, proteomics, and epigenomics.

• Tissue specificity matters: Most available molecular data come from blood samples, but disease-relevant regulation happens in diverse tissues. Without this diversity, causal variants may be missed or misinterpreted.

• Examples of progress: Initiatives like GTEx, TOPMed, and the Human Cell Atlas provide initial steps toward inclusive molecular catalogs—but sample sizes and tissue variety for non-European ancestries remain small and underpowered.

• Call to action: The authors propose increased funding, infrastructure, community engagement, and global collaboration to fill these gaps. Analytical methods must evolve to handle ancestry-aware integration of complex omics data.

This episode is a wake-up call: advancing equity in human genomics isn’t optional—it’s essential. Only by embedding diversity across every layer of genomic research can we realize the full potential of personalized medicine for all populations.

📖 Reference:
Arruda, A.L., Morris, A.P., & Zeggini, E. (2024). Advancing equity in human genomics through tissue-specific multi-ancestry molecular data. Cell Genomics, 4(2), 100485. https://doi.org/10.1016/j.xgen.2023.100485

📜 License:
This episode is based on an open access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

🎙️ Episode Title: What Makes Us Human? Genetics from Neandertals to Now

🧬 In this episode of Base by Base, we travel back in time—over 600,000 years—to explore the genomic storylines of Neandertals, Denisovans, and modern humans. Published in Cell by Hugo Zeberg, Mattias Jakobsson, and Nobel Laureate Svante Pääbo, this comprehensive review deciphers the evolutionary divergences that defined—and continue to define—our species.

By comparing high-quality genomes from extinct and extant human lineages, the authors provide a sweeping analysis of the genetic variants that shaped brain function, metabolism, immunity, reproduction, and adaptation to diverse environments.

🔍 Key insights include:

• Archaic legacy: 2% of the genome in non-African individuals today comes from Neandertals; in Oceania, over 5% derives from Denisovans.

• Disease and adaptation: Some Neandertal variants increase risk for conditions like severe COVID-19 and autoimmune disease—yet others provide resistance to infections like Helicobacter pylori and HIV.

• Denisovan traces: Modern Tibetan populations inherited a Denisovan variant in EPAS1, aiding adaptation to high altitudes.

• Brain development: Modern human-specific changes in genes like TKTL1, KNL1, and KIF18A influence early neurogenesis and chromosomal segregation—potential contributors to our cognitive evolution.

• The combinatorial human: Rather than a single “modern” genetic signature, humans today carry a mosaic of derived and ancestral alleles—defining our species by combinations of variants, not absolutes.

• Experimental revival: Using CRISPR, organoids, and mouse models, researchers are now resurrecting archaic variants to study their effects in human cells and model organisms.

• Rewriting assumptions: Several variants thought to be exclusive to modern humans are found in ancestral form in present-day populations—especially in Africa and the Philippines.

This landmark review redefines human uniqueness through a genomic lens, not as a checklist of fixed traits, but as a dynamic ensemble of evolutionary possibilities. It’s a must-listen for anyone intrigued by how ancient DNA continues to shape our biology, health, and identity.

📖 Reference:
Zeberg, H., Jakobsson, M., & Pääbo, S. (2024). The genetic changes that shaped Neandertals, Denisovans, and modern humans. Cell, 187. https://doi.org/10.1016/j.cell.2023.12.029

📜 License:
This episode is based on an open access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

🎙️ Episode Title: Beyond the Genome: Societal Value of National Genomics Programmes

🧬 In this episode of Base by Base, we discuss a thought-provoking report published in the European Journal of Human Genetics that tackles a crucial yet underexplored question: what is the actual value of large-scale national genomic programmes for society?

Led by Ruth Horn, Angeliki Kerasidou, Jennifer Merchant and the UK-FR+GENE consortium, this multidisciplinary workshop brought together ethicists, geneticists, economists, clinicians, and policymakers from across Europe. Their goal was to define how these programmes contribute to public good—scientifically, economically, and socially.

🔍 Key insights include:

• Trust and Transparency: Public trust is essential but fragile. While rigorous data governance can help, ongoing concerns about data privacy and public-private partnerships must be addressed transparently.

• Economic Gaps: Despite major investments, there is still a lack of robust evaluations on the cost-effectiveness of large sequencing programmes. Without economic frameworks, the opportunity costs for public health remain unquantified.

• Clinical Impacts: While many patients benefit from genomic diagnosis—especially in rare diseases—others experience uncertainty or frustration when no actionable outcome is available. Professionals often navigate this with cautious optimism.

• Scientific Caution: While technologies like polygenic risk scores and whole-genome sequencing promise precision, their predictive power is still limited in many common diseases. Interpretation challenges persist in the clinic.

• Population-Level Dilemmas: Genomic medicine has the potential to inform public health strategies, but equitable access and demonstrable outcomes are still lacking. Minority and underserved groups risk being left behind.

• Call to Action: The authors advocate for clearer criteria when rolling out large-scale genomic initiatives—avoiding overpromising, prioritizing equity, integrating cost assessments, and respecting the nuanced experiences of patients and families.

This episode explores how genomics must not only advance science, but also demonstrate meaningful, measurable benefits to society at large—especially in solidarity-based healthcare systems. Without this balance, the promise of genomic medicine risks being overshadowed by overreach.

📖 Reference:
Horn, R., Kerasidou, A., Merchant, J., et al. (2025). The value of large-scale programmes in human genomics. European Journal of Human Genetics. https://doi.org/10.1038/s41431-025-01844-7

📜 License:
This episode is based on an open access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/