Skip to main content
HHMI BioInteractive
  • Español
  • Site Search
  • Log In/Create Account
  • BioInteractive Resources
  • Planning Tools
  • Professional Development
  • About Us

Inheritance and Mutations in a Single-Gene Disorder

Screenshot of a portion of a genealogy diagram

Topic

  • Biochemistry & Molecular Biology
  • Biotechnology
  • Genetics
  • Patterns of Inheritance
  • Genetic Disease

Resource Type

  • Activities
  • Lessons

Level

High School — GeneralHigh School — AP/IBCollege
Saved By
57 Users
Share This

Description

This activity builds on information presented in the short film Genes as Medicine. Students interpret actual pedigrees to determine the inheritance pattern of Leber congenital amaurosis (LCA), an inherited form of blindness. They also examine protein sequence data to explore mutations that can cause LCA.

LCA is a disease that primarily affects the retina. Scientists have identified several types of LCA with different genetic causes and patterns of vision loss. In this three-part activity, students examine a form of LCA caused by mutations in the gene RPE65. 

The activity reinforces the connection between genotype and phenotype and illustrates that genes can have multiple alleles, including multiple disease-causing alleles. In the first part of the activity, students analyze several pedigrees of families with members who have LCA. The pedigrees were obtained from a published scientific study. In the second part, students explore mutations in the RPE65 protein in individuals with LCA and discover that some individuals (known as compound heterozygotes) carry two different disease-causing alleles. In the last part of the activity, students reflect on how LCA can be treated using gene therapy.

The “Resource Google Folder” link directs to a Google Drive folder of resource documents in the Google Docs format. Not all downloadable documents for the resource may be available in this format. The Google Drive folder is set as “View Only”; to save a copy of a document in this folder to your Google Drive, open that document, then select File → “Make a copy.” These documents can be copied, modified, and distributed online following the Terms of Use listed in the “Details” section below, including crediting BioInteractive.

Student Learning Targets

  • Describe the relationship between genotype and phenotype.
  • Use a pedigree to infer genotypes and determine the most likely inheritance pattern of a single-gene trait.
  • Analyze amino acid sequence data to identify mutations.
     

Estimated Time

One 50-minute class period if the film is watched outside of class. Two 50-minute class periods may be needed to watch the film in class and/or review basic genetics concepts.

Key Terms

allele, compound heterozygote, gene sequencing, gene therapy, genotype, Leber congenital amaurosis (LCA), pedigree chart, phenotype

Primary Literature

Morimura, Hiroyuki, Gerald A. Fishman, Sandeep A. Grover, Anne B. Fulton, Eliot L. Berson, and Thaddeus P. Dryja. “Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis.” Proceedings of the National Academy of Sciences 95, 6 (1998): 3088–3093. https://doi.org/10.1073/pnas.95.6.3088. 

Li, Yumei, Hui Wang, Jianlan Peng, Richard A. Gibbs, Richard Alan Lewis, James R. Lupski, Graeme Mardon, and Rui Chen. “Mutation survey of known LCA genes and loci in the Saudi Arabian population.” Investigative Ophthalmology and Visual Science 50, 3 (2008): 1336–1343. https://doi.org/10.1167/iovs.08-2589. 

Russell, Stephen, Jean Bennett, Jennifer A. Wellman, Daniel C. Chung, Zi-Fan Yu, Amy Tillman, Janet Wittes, et al. “Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: A randomised, controlled, open-label, phase 3 trial.” The Lancet 390, 10097 (2017): 849–860. https://doi.org/10.1016/s0140-6736(17)31868-8.
 

Terms of Use

The resource is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International license. No rights are granted to use HHMI’s or BioInteractive’s names or logos independent from this Resource or in any derivative works.

Accessibility Level (WCAG compliance)

PDF files meet criteria.

Version History

Date Published 09.26.19
Date Updated 04.29.20

NGSS (2013)

HS-LS1-1, HS-LS3-1; SEP2, SEP6

AP Biology (2019)

IST-1.I, IST-1.N, IST-1.P, IST-2.E, IST-4.A, SYI-3.C; SP1, SP2, SP6

IB Biology (2016)

3.1, 3.4, B.4

Common Core (2010)

ELA.RST.9–12.4, ELA.RST.9-12.7
Math.S-IC.2; MP2, MP4
 

Vision and Change (2009)

CC3; DP3

Materials

Resource Google Folder (link)
Educator Materials (PDF) 694 KB
Student Handout (PDF) 549 KB

Use This Resource With

Video Resource
Genes as Medicine

Explore Related Content

Other Related Resources

Showing of
Image illustrating heterozygosity from the film
Film Activities
Activity for Genes as Medicine
Computer image from the film of a virus
Short Films
Genes as Medicine
Computer image of a patient from the virtual lab
Virtual Labs
Cardiology Virtual Lab
Computer illustration of a pedigree
Lessons
Analyzing Pedigrees
Image from the activity
Data Points
Origin of a Gene Mutation Causing Early-Onset Alzheimer’s Disease
An illustration of sickled red blood cells clogging a blood vessel
Scientists at Work
A Genetic Treatment for Sickle Cell Disease
Illustration of chromosomes with bands representing genes
Interactive Videos
Interactive Case Study for The Search for a Mutated Gene
Image from the film of a man looking into an eyesight device
Scientists at Work
The Search for a Mutated Gene
Image from the activity
Case Studies
DNA Profiling Activity
Illustration of RNA translation
Click & Learn
Central Dogma and Genetic Medicine
HHMI BioInteractive
  • Facebook
  • Instagram
  • Twitter
  • YouTube
  • Newsletter Signup
  • HHMI.org
  • Terms of Use
  • Privacy Policy
  • Accessibility