IDS 123A: 2026 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: Now available on CLE page.

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

Instructor: Diego Calderon

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

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.

Slides: Now available on CLE page.

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

Instructor: Diego Calderon

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:

  • 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: Now available on CLE page.

Day 4: Modern Complex Traits Genetics

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

Location: Mission Hall 1407

Instructor: Diego Calderon

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.
  • Estimation and mapping of the missing heritability of human phenotypes. PMID: 41225014.

Slides: Now available on CLE page.

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

Example 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

Slides: Now available on CLE page.

Day 6: Genetics and Human Health

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

Location: Mission Hall 1407

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

  • Dissecting gene regulatory elements
  • Regulatory elements as therapeutic targets

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

  • Synthesis and key takeaways from the course
  • Showcase discussion

Reading:

  • Implantation of engineered adipocytes suppresses tumor progression in cancer models. PMID: 39905264

Slides: Now available on CLE page.

Additional Resources

  • Open Targets: https://platform.opentargets.org
  • GWAS Catalog: https://www.ebi.ac.uk/gwas/
  • UCSC Genome Browser: https://genome.ucsc.edu/
  • Washington University Genome Browser: https://genome.wustl.edu/
  • ENCODE Portal: https://www.encodeproject.org
  • GTEx Portal: https://www.gtexportal.org/