Course Slide Decks & Materials
📜 Full Syllabus & Grading →Genomics in Medicine & The AI Frontier
Deconstructs foundational myths in modern medicine: why "normal" reference intervals are statistical fictions, how 1750 London infant mortality distorted life expectancy, the evolutionary scar of the Black Death, the economic trap of blockbuster clinical trial averages, and how structure-based genomics cured CML.
- Gaussian Distributions & Lab Intervals
- 1,000 Years of Mortality Dynamics
- The 7 Axes of Disease
- Ancient DNA & ERAP2 Immune Selection
- Evidence-Based Medicine vs. NNT
- CML & BCR-ABL Kinase Inhibition
- Live PGx Database Investigation
The Architecture of the Human Genome: Physical Molecules, Ploidy & The Missing 8%
From digital 1D code to 3D nuclear chromatin, chromosome mechanical segregation, mitochondrial heteroplasmy bottlenecks, the genetics of cis/trans phasing, the historical evolution of the gene concept, and how the Telomere-to-Telomere (T2T) consortium finally finished the 20-year missing 8%.
- Digital Code vs 3D Macromolecule
- 8 Orders of Magnitude Genome Sizes
- Chromosome Anatomy & Chr 2 Fusion
- mtDNA Heteroplasmy & Thresholds
- Diploidy & Phasing (Cis vs Trans)
- Smartphone Storage Analogy
- C-Value Enigma
- Mendel, Morgan, Avery & The Gene
- The Great Gene Count Collapse
- T2T Consortium (Nurk et al. 2022)
- Focus 1: Abstract & Introduction — Why was ~8% of the human genome missing for 20 years?
- Focus 2: Figure 1 & Figure 2 — GRCh38 gaps vs. T2T closed chromosomes; what was hidden inside the heterochromatic repeats?
- Focus 3: Section "Clinical Implications" — How unresolved repeats caused false-positive clinical variant calls.
Thousands of Tiny Nudges: GWAS, Complex Traits, and Polygenic Risk Scores
From monogenic Mendelian certainties to Fisher's infinitesimal model. Genome-Wide Association Studies (GWAS), Linkage Disequilibrium, Manhattan plots, within-family sibling controls, and the hype audit of Polygenic Indices (PGIs).
- Polygenic & Omnigenic Architecture
- 1,260 Lead SNPs (N > 1.14M)
- Missing Heritability & Reliability
- Debunking Neurotransmitter Dogma
- Within-Family Sibling GWAS
- Minimal Familial Confounding
- Spousal Assortative Mating (r_g ≈ 0)
- PGI Predictive Limits (R² ≈ 1-3%)
- Focus 1: Table 1 & Figure 1 — 1,260 lead SNPs; 82% trait-specific architecture vs. overlapping prefrontal cortex gene sets.
- Focus 2: Figure 4 & Section "Within-Family Analyses" — Sibling controls proving minimal familial confounding compared to educational attainment.
- Focus 3: Figure 2 & The Hype Audit — Why PGIs explain only 1%–3% of variance and cannot predict individual future behavior.