IDS 123A: 2025 Inquiry Immersion

Mini-course on using genetics to understand human biology and disease

Instructors

Overview

What can genetics teach us about human biology, disease, and discovering new drugs? In this mini-immersion, students will explore how large-scale human genetic data are generated and analyzed, and how these insights can inform mechanisms of disease and guide drug discovery.

Learning Objectives

By the end of this course, students will be able to:

  1. Explain key concepts, techniques, and landmark discoveries in modern human genetics.

  2. Analyze large-scale genomic datasets and public resources to assess the relevance of genetic variation to human disease.

  3. Formulate hypotheses about how specific DNA mutations may influence human phenotypes and identify potential therapeutic targets.

Course Schedule

Day 1: Overview and Genetic Resources

Date/Time: Tuesday, January 6, 2026 3:00 PM - 5:00 PM

Location: Mission Hall 1407

Instructor: Diego Calderon

Topics:

  • The power of genetics for drug discovery
  • The DNA-sequencing revolution: from $3 billion to $1,000
  • How do we do modern genetics? Introduction to GWAS (Genome-Wide Association Studies)
  • Available resources for interpreting genetic variation
  • Exploring the UCSC Genome Browser and Washington University Genome Browser
  • GTEx Portal: exploring gene expression across tissues

Reading:

  • Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. PMID: 17554300
  • Genetic dissection of complex traits. PMID: 8091226
  • How to interpret a genome-wide association study. PMID: 18349094
  • Refining the impact of genetic evidence on clinical success. PMID: 38632401

Slides: [Coming soon]

Day 2: Connecting Genetics to Mechanisms: Understanding Gene Regulation - Part 1

Date/Time: Wednesday, January 7, 2026 3:00 PM - 5:00 PM

Location: Mission Hall 2106

Topics:

  • Surprise, most GWAS are non-coding.
  • ENCODE Project: mapping regulatory elements across the genome
  • Expression Quantitative Trait Loci (eQTLs): linking genetic variants to gene expression
  • Massively Parallel Reporter Assays (MPRA): testing the functional effects of DNA sequences
  • CRISPR-based approaches: editing and interrogating the genome towards treating disorders

Reading:

  • ENCODE project writes eulogy for junk DNA. PMID: 22955811
  • Systematic Localization of Common Disease-Associated Variation in Regulatory DNA. PMID: 22955828
  • Understanding mechanisms underlying human gene expression variation with RNA sequencing. PMID: 20220758
  • Genome-wide quantitative enhancer activity maps identified by STARR-seq. PMID: 23328393
  • Modulating gene regulation to treat genetic disorders. PMID: 33020616
  • CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency. PMID: 30545847

Slides: [Coming soon]

Day 3: Connecting Genetics to Mechanisms: Understanding Gene Regulation - Part 2

Date: Thursday, January 8, 2026 3:00 PM - 5:00 PM

Location: Mission Hall 2106

Topics:

  • Massively Parallel Reporter Assays (MPRA): testing the functional effects of DNA sequences
  • CRISPR-based approaches: editing and interrogating the genome
  • From association to function: using experimental approaches to understand disease variants

Reading:

  • Moving over articles from part 1 since it’s overloaded.

Slides: [Coming soon]

Day 4: Modern Complex Traits Genetics

Date/Time: Friday, January 9, 2026 3:00 PM - 5:00 PM

Location: TBD

Topics:

  • The case of missing heritability: why we can’t explain all genetic contributions to traits
  • The omnigenic model: reconceptualizing how genetic variants influence traits
  • Interpreting polygenic effects in human genetics. It’s not just about effect size.

Reading:

  • The case of the missing heritability. PMID: 18987709.
  • Finding the missing heritability of complex diseases. PMID: 19812666
  • An Expanded View of Complex Traits: From Polygenic to Omnigenic. PMID: 28622505
  • Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. PMID: 30104762

Slides: [Coming soon]

Day 5: Great Power and Great Responsibility - Ethics and Genetics

Date/Time: Tuesday, January 13, 2026 1:30 PM - 3:30 PM

Location: Mission Hall 1407

Guest Lecturer: Dara Torgersen

Topics:

  • Representation and inclusion in global genome collections
  • Ethical considerations surrounding the use of genetics in forensics
  • Reproductive technologies and genetic information
  • Personalized medicine: benefits and concerns

Reading:

  • TBD article Dara might discuss.

Slides: [Coming soon]

Day 6: Genetics and Human Health

Date/Time: Thursday, January 15, 2026 3:00 PM - 5:00 PM

Location: Mission Hall 2109

Guest Lecturer (3:00 PM - 4:00 PM): Nadav Ahituv

  • Discussion of disease variants and therapeutic strategies

Course Wrap-up (4:00 PM - 5:00 PM): Diego Calderon

  • Synthesis and key takeaways from the course

Reading:

  • TBD article Nadav might discuss.

Slides: [Coming soon]

Additional Resources

  • GTEx Portal: https://www.gtexportal.org/
  • UCSC Genome Browser: https://genome.ucsc.edu/
  • Washington University Genome Browser: https://genome.wustl.edu/
  • GWASCatalog: https://www.ebi.ac.uk/gwas/