Mendelspod Podcast

The future of genomics has arrived in Abu Dhabi.On today’s show, Dr. Mohamed Alameri of the UAE Department of Health and Albarah El-Khani of M42 describe one of the most ambitious precision medicine efforts underway anywhere in the world: the Emirati Genome Program, which has already sequenced more than 900,000 genomes and is rapidly integrating that data into everyday healthcare.The UAE program is not only a large sequencing effort and database—soon to be made available for research anywhere—but a coordinated national strategy built on prevention, diagnosis, and long-term population health. Particularly striking is the UAE’s focus on inherited and autosomal recessive diseases, which occur at significantly higher prevalence in the region than in many Western populations. Rather than treating genomics as an isolated research exercise, the program has pushed aggressively into premarital screening, newborn genomic screening, pharmacogenomics, hereditary cancer risk assessment, and rare disease diagnosis. “We truly believe in the philosophy of ‘sequence once, analyze for life,’” says El-Khani. “Imagine a society where every individual from birth holds a whole genome sequence throughout their life. How powerful is that tool at every intersection of public health, clinical care, and screening?”The scale of the project is already yielding discoveries difficult to achieve elsewhere. According to Alameri, roughly 12% of the variants identified in the Emirati population are not represented in existing global databases, underscoring just how underrepresented Middle Eastern populations remain in genomics research. In some cases, variants previously considered pathogenic in European populations appear to behave differently in Emirati patients, opening entirely new biological questions.Perhaps the most impressive aspect of the program is the degree to which genomics has been operationalized across the healthcare system. The UAE has invested heavily in physician education and public engagement to move genomics from bench to bedside. Our guests describe a healthcare ecosystem where genomic reports, pharmacogenomic guidance, and hereditary risk assessments are increasingly available directly within clinical workflows.“The vision was not sequencing everyone for its own sake,” says Dr. Alameri. “It was to build a national asset that could support more predictive, preventative, personalized healthcare for our population and for future generations.”There is always hype in genomics, as with other emerging technologies. But the UAE effort is already very comprehensive and clinically grounded. This is genomics functioning as healthcare infrastructure in real time. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

“We have been talking now for 15, 20 years about the diagnostic odyssey. That shouldn’t exist anymore. The new odyssey is the therapeutic odyssey.”That’s Stephen Kingsmore, president and CEO of Rady Children’s Hospital (he just announced his retirement), explaining the impact of a new genome mapping technology from Illumina.Whole-genome sequencing has transformed diagnosis, but some of the hardest pediatric cases persist because the structure of the genome has remained difficult to resolve. Today on Mendelspod, we cover Illumina’s newly launched proximity mapped reads, showing how long-range genomic context can be captured directly on existing Illumina sequencers and integrated into the lab workflow. The conversation traces how this added structural clarity is already improving diagnostic confidence and, critically, enabling highly precise n-of-1 therapies such as antisense oligonucleotides (ASOs).Olivia Kim-MacManus, a pediatric neurologist and ASO trial leader, shows how the new diagnostic precision directly feeds therapeutic design. “All of these genetic therapy approaches hinge on precise diagnostics,” she notes, emphasizing that allele-specific and haplotype-aware targeting is essential for ASOs and other emerging gene-based interventions.From the product and workflow side, Ali Crawford joins us as Senior Director of Science Research at Illumina, detailing how the technology works without requiring new instruments or complex workflows, eliminating the need for separate library preparation steps.“You just order the kit and go,” she says, highlighting how preserving spatial information on the flow cell unlocks variant calls and structural insight that were previously inaccessible with their standard short-read sequencing.When genome structure comes into better focus, treatments are no longer theoretical. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Large-scale genomics is back — and this time, it’s global by design.In this episode of Mendelspod, we return to the kind of ambitious, shared genomics project that helped define the field a decade ago. The Global Parkinson’s Genetics Program (GP2) has now genotyped more than 100,000 participants worldwide, with roughly one third of samples coming from historically underrepresented populations. That scale and diversity are already reshaping how Parkinson’s disease is studied — and how it may eventually be treated.My guests are Andrew Singleton, co-lead of GP2, and Ignacio (Nacho) Mata, a geneticist at Cleveland Clinic and founder of the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD). Together, they describe how globally representative datasets are not a political aspiration, but a scientific necessity — especially in an era of precision medicine.Singleton explains that studying Parkinson’s across populations doesn’t just broaden participation; it increases scientific power. “The more we learn about individual populations, the more we understand about disease as a whole — and the more chances we have to come up with treatments for disease as a whole,” he says. Mata brings a complementary perspective from years of building Parkinson’s genetics infrastructure in Latin America. He emphasizes that without inclusion in genetic and biomarker research, entire populations risk being excluded from the next generation of molecularly targeted therapies. “If we don’t have our patients studied for genetics or biomarkers, then those patients will not have access to the new treatments,” he notes, adding that GP2 is designed to narrow rather than widen existing health disparities.We explores how GP2’s open-science structure has been key to its success and could serve as a model for other global research projects. GP2 has invested heavily in training and infrastructure so that researchers around the world can lead analyses locally, rather than simply contributing samples.As both guests make clear, this is only the beginning. With hundreds of thousands of samples committed and a new generation of globally distributed investigators, GP2 is laying the groundwork for biologically defined subtypes of Parkinson’s and for more precise diagnostics and disease-modifying therapies.When genomics gets big enough — and inclusive enough — scale itself becomes a discovery. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

For today’s show, we return to discussing the exciting new Cellanome platform. Joining Theral are Pier Federico Gherardini, VP of Computational Biology at Cellanome, and Matthew Spitzer, Associate Professor at University of California, San Francisco, whose lab is using Cellanome’s CellCage technology to study immune cells in dynamic, interactive contexts.0:00 From static snapshots to observing cell function in real time4:45 Pairing phenotype with function like we never could before7:30 Can see cell-cell interaction19:40 Early applicationsRather than relying on static single-cell snapshots, the Cellanome platform enables longitudinal observation of live cells—tracking division, interaction, and function over time—before pairing those behaviors with transcriptomic and molecular readouts. As Gherardini explains, “This creates essentially a new data type where you observe cells over time… and then you can pair all of that functional information with the molecular readouts that you get from sequencing.”For Spitzer, that shift fundamentally changes what can be known. Traditional approaches often force scientists to infer function indirectly, correlating phenotype measured in one experiment with behavior measured in another. With CellCage, his lab can finally measure both in the same individual cell. “Now we have measured the function of the cell and the phenotype for the same exact individual cell,” Spitzer says, “and this allows us to really understand how those core characteristics are linked in a much more detailed way.”For Spitzer, a major advance comes from observing cell–cell interactions as they unfold. Where previous methods could show proximity in a tissue section, they could not reveal outcomes. Using Cellanome, Spitzer’s team can now watch whether a T cell activated by a dendritic cell actually proliferates, produces effector molecules, or kills a tumor cell—and then trace those outcomes back to specific molecular programs. This has already revealed surprising heterogeneity within supposedly uniform cell populations, identifying rare but highly potent immune cells that would have been invisible in bulk assays.Looking ahead, both guests see immediate applications in cell therapy development, target discovery, and functional CRISPR screening—areas where measuring what cells actually do matters more than what they merely express. We close with a sense that cell biology is entering a new phase—one where function, interaction, and time are no longer inferred, but directly observed, measured, and modeled. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe