Clinical Genetics

Sequenced but Stranded: The Millions of Rare Variants Medicine Cannot Yet Explain

Whole-genome sequencing can now identify millions of rare genetic variants in a single patient, yet the vast majority of those variants exist in a scientific void—unstudied, uncharacterized, and clinically uninterpretable. For patients with undiagnosed rare diseases, this gap between discovery and understanding can mean years of uncertainty or a lifetime without answers. Understanding why so many mutations remain medically invisible is essential to fulfilling the promise of precision medicine.

Sep 21, 2026

Thousands of Variants, One Imperfect Number: The Limits of Polygenic Risk Scores in Clinical Practice

Polygenic risk scores aggregate information from thousands of genetic variants to estimate disease susceptibility, but translating that statistical signal into meaningful clinical guidance remains an elusive challenge. Gaps in population diversity, environmental complexity, and model assumptions all conspire to limit real-world accuracy. Understanding what these scores can and cannot tell us is now an essential competency for clinicians and patients alike.

Aug 19, 2026

One Body, Many Genomes: The Science of Somatic Mosaicism and Its Clinical Consequences

The foundational assumption that every cell in a human body carries identical DNA is, strictly speaking, incorrect. Somatic mosaicism—the presence of genetically distinct cell populations within a single individual—is more widespread than previously recognized and carries significant implications for cancer risk, rare disease diagnosis, and the interpretation of genetic test results. Advances in high-sensitivity sequencing are revealing a genomic complexity that challenges long-held assumptions

Jul 15, 2026

Variants of Uncertain Significance: Navigating the Gray Zone of Genomic Interpretation

Modern sequencing technology has outpaced our ability to interpret what it finds, leaving a vast category of genetic variants without a clear clinical meaning. Known as variants of uncertain significance, these genomic question marks present real challenges for patients and clinicians alike. Understanding how researchers are working to resolve this uncertainty is essential for anyone engaging with genetic testing today.

Jul 15, 2026

Same Genes, Different Fates: The Science of Why Genetic Risk Is Not Genetic Certainty

Carrying a genetic variant associated with heart disease, diabetes, or Alzheimer's does not guarantee that disease will ever materialize. Emerging research into penetrance and phenotypic plasticity is fundamentally reshaping how clinicians and scientists communicate genetic risk to patients. Understanding this distinction may be one of the most consequential shifts in modern medicine.

Jul 13, 2026

From Bench to Bedside: CRISPR Gene Editing Enters the Era of Approved Medicine

Once confined to research laboratories, CRISPR-based therapies have crossed a historic threshold with FDA approvals that are reshaping what is possible for patients with previously untreatable genetic diseases. This milestone marks not just a scientific achievement, but a fundamental shift in how medicine addresses the root causes of inherited conditions. The journey from discovery to clinic, however, carries important questions about access, equity, and the long-term responsibilities of a socie

Jul 8, 2026