Family Markers: Using Multiply-Affected Families to Identify Risk Genes

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Overview

This activity teaches students to interpret pedigree information and use bioinformatics tools (R) to build pedigrees for tracking disease traits in families. Students will work with real data from a bipolar disorder genetics study to understand how researchers understand risk genes using pedigrees.

Duration: Approximately 2-3 hours (depending on student familiarity with R)

Learning Objectives

  1. Interpret pedigree information to determine the suitability of a DNA marker for tracking a disease trait in a family (see GSA learning objectives).

  2. Build a pedigree using bioinformatics tools (R).

Materials and Setup

  • Students will need either:

    • An internet connection for this activity as written (using Posit Cloud)
    • A local installation of R or RStudio (with data downloaded and kinship2 package installed ahead of time)

  • Required R package: kinship2

  • Data hosting: https://genomicseducation.org/data/pedigree_data.csv

  • Download the R student activity as:

  • Google Slides presentation available for borrowing images here.

  • Answer key available here. Please message Ava Hoffman (ahoffma2 at fredhutch dot org) to get access.

Scientific Topics

The activity is based a published research study “Rare variants implicate NMDA receptor signaling and cerebellar gene networks in risk for bipolar disorder.” Students will gain exposure to the following:

  • Bipolar Disorder: Neuropsychiatric condition affecting ~1% of population, with 10-25% risk for children of affected parents

  • Cerebellum: Brain region containing 50% of neurons despite being 10% of brain volume; involved in motor coordination and emotional regulation

  • NMDA Receptors: Glutamate receptors crucial for memory and learning; blocked by substances like alcohol and ketamine

  • DAO Gene: D-amino acid oxidase gene identified as significantly associated with bipolar disorder risk

Outline

  • Part 1: Background and Setup (30-45 minutes)

  • Part 2: Basic Pedigree Construction (20-30 minutes)

  • Part 3: Adding Diagnostic Information (15-20 minutes)

  • Part 4: Genotype Mapping and Analysis (30-40 minutes)