Activity 1-2 - Human Genetic Inheritance and Diseases
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- Jun 19, 2025
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- Define a gene mutation and distinguish it from deletions and duplications.
- Identify a human monogenic disease caused by a point or repeat mutation.
- Use OMIM and NCBI to locate a gene, identify the associated mutation, and determine its effects on protein function.
- Describe how a gene mutation translates into phenotypic symptoms and impacts life expectancy.
- Determine the inheritance pattern (autosomal dominant/recessive or X-linked) of a genetic disease.
- Navigate DNA, mRNA, and protein sequences using NCBI Gene and NCBI Protein databases.
- Analyze how genetic mutations disrupt protein function, contributing to disease.
- Mutation: A change in the DNA sequence (e.g., substitution, insertion, or expansion).
- Monogenic Disorder: A disease caused by mutation in a single gene.
- Point Mutation: A single base substitution in DNA that can change a protein’s function.
- Repeat Expansion: A mutation where a short DNA sequence is repeated more times than normal.
- Genotype: An individual's combination of alleles for a gene.
- Phenotype: Observable traits or symptoms that result from genotype.
- Inheritance Pattern: The way a trait or disease is passed down (dominant, recessive, X-linked).
- NCBI Gene: A database used to find genes, sequences, and genomic context.
- OMIM: Online Mendelian Inheritance in Man—a database of human genetic disorders.
- NP Accession Number: A unique identifier for a specific protein sequence in NCBI.
- Genes are blueprints for proteins.
- Mutations (like point substitutions or repeat expansions) can disrupt protein structure/function.
- Diseases like Cystic Fibrosis, Sickle Cell Anemia, and Huntington's Disease are monogenic but differ in mutation type and inheritance.
- Not all genetic diseases are caused by big chromosomal changes—this activity focuses on point mutations and repeat expansions only.
- Review how DNA → RNA → Protein works (Central Dogma).
- Familiarize yourself with basic gene structure: exons, introns, coding vs. non-coding regions.
- Visit OMIM and NCBI Gene and explore example genes like CFTR, HBB, or HTT.
- Think about the relationship between genetic mutation and disease phenotype.
- Bring your laptop and a willingness to explore!
Activity 1-2A: Researching Human Genetic Diseases
Background
Genetic diseases are caused by changes—or mutations—in an organism’s DNA sequence. These mutations can occur in a single gene or across multiple genes, and their effects range from mild to severe. In this activity, you will investigate a monogenic (single-gene) disorder caused by a specific mutation, not a deletion or duplication. You'll explore where in the genome the gene is located, what goes wrong in the gene, how it affects people, and how it's inherited. A mutation is a change in the DNA sequence of a gene. This might be as small as a single-letter substitution (called a point mutation), or as big as inserting or removing segments. For this activity, focus on mutation-based diseases, like:
- Cystic Fibrosis (CFTR gene, Chromosome 7) – Caused by a point mutation (most commonly ∆F508) that results in thick, sticky mucus buildup.
- Sickle Cell Disease (HBB gene, Chromosome 11) – A single base substitution leads to the production of abnormal hemoglobin, affecting red blood cells.
- Huntington’s Disease (HTT gene, Chromosome 4) – Caused by a repeat expansion mutation leading to progressive brain degeneration.
Do not choose disorders that are due to large deletions or duplications of genes or entire chromosome segments (e.g., Down syndrome caused by trisomy 21 is not allowed).
Your DNA is packaged into 23 pairs of chromosomes, each carrying hundreds to thousands of genes. Every gene has a specific “address” on a chromosome. For example, the CFTR gene is found on chromosome 7. In this activity, you’ll pick one chromosome, find a mutated gene located there, and research the genetic disease it causes. Each gene has two copies (alleles), one from each parent. Depending on the mutation and the gene, diseases can follow different modes of inheritance:
- Autosomal Dominant (AD): Only one mutated copy is needed to cause the disease (e.g., Huntington’s).
- Autosomal Recessive (AR): Both gene copies must be mutated for the disease to appear (e.g., Cystic fibrosis).
- X-linked: The mutated gene is on the X chromosome. Since males have one X and one Y, they are more affected by X-linked recessive diseases (e.g., Duchenne muscular dystrophy).
This investigation helps you link genotype (DNA mutation) to phenotype (observable traits)—a key theme in genetics. You’ll use OMIM and NCBI to find:
- The gene responsible for the disease.
- The DNA sequence (in base pairs).
- How the mutation alters gene function.
- What phenotypic traits (symptoms) appear.
- Inheritance pattern, and how long individuals with the disease typically live.
Instructions:
- Choose any chromosome (1–22, or X/Y). Use the NCBI, Google, or ChatGPT to explore it.
- Scroll through the gene list and click to learn more about each one. Choose a gene that is known to cause a disease due to mutation, not deletion or duplication. You can also search for diseases in OMIM and trace them back to their gene.
- Once you’ve chosen a gene and its associated disease, fill out Table 1-2A with the following:
- Names of your group members (or individual)
- Chromosome number
- Disease name
- Gene name (must be on selected chromosome)
- Mode of inheritance (Autosomal Dominant or Autosomal Recessive)
- Number of base pairs in the gene
- Life expectancy of individuals with the disease
- Most common symptoms
- One student per group will submit the completed table before the end of class.
Table 1-2A: Genetic Disease Research Summary
| Group Members | Chromosome Number | Disease Name | Gene Name | Inheritance (AD/AR) | Gene Size (Base Pairs) | Life Expectancy | Common Symptoms |
|---|---|---|---|---|---|---|---|
Example: Table 1-2A – Genetic Disease Research Summary
| Group Members | Chromosome Number | Disease Name | Gene Name | Inheritance (AD/AR) | Gene Size (Base Pairs) | Life Expectancy | Common Symptoms |
|---|---|---|---|---|---|---|---|
| Alex, Jordan, Sam | 7 | Cystic Fibrosis | CFTR | Autosomal Recessive | ~189,000 bp | Median: ~40–50 years (with treatment) | Thick mucus in lungs, chronic lung infections, poor growth, salty sweat, infertility |
Activity 1-2B: Exploring Gene and Protein Sequences
This activity helps you visualize how genetic information flows from DNA to RNA to protein, a process known as the Central Dogma of Molecular Biology. When a mutation occurs in a gene, it can affect the structure or function of the protein that the gene codes for. This is often the root cause of many genetic diseases. For example, the BRCA1 gene (linked to breast and ovarian cancer) is located on chromosome 17. When functioning properly, the BRCA1 protein helps repair damaged DNA. A mutation in BRCA1 can lead to a malfunctioning protein, increasing cancer risk because damaged DNA isn’t properly repaired. In this activity, you will retrieve and analyze different forms of your gene’s sequence:
- Genomic DNA (NC_ or NG_): The full stretch of DNA that includes the gene, including introns (non-coding regions) and exons (coding regions).
- mRNA (NM_ or XM_): This is the “cleaned-up” transcript with introns removed—what the ribosome reads to build a protein.
- Protein (NP_ or XP_): This is the final, functional product. You’ll explore its name, function, and sequence.
Protocol
- Using either NCBI, Google, or ChatGPT to determine the name of the protein that your gene expresses.
- Visit NCBI protein (i.e., https://www.ncbi.nlm.nih.gov/protein)
- Input your protein's name in the search bar. (Make sure the proteins belongs to Homo sapeins)
- Click on the correct protein entry and scroll down the page on the website, and copy the full protein sequence
- On the same webpage, you can find and copy the NP accession number or GeneBank code
- Save the sequence of NP code for the next lab.
Data Collection Table for Activity 1-2B
| Group Members | Gene Name | Disease Name | Protein Name | Protein Sequence | NP Accession # | Notes on Protein Function |
|---|---|---|---|---|---|---|
Example Entry: BRCA1
| Group Members | Gene Name | Chromosome Number | Disease Name | Protein Name | NP Accession # | Notes on Protein Function |
|---|---|---|---|---|---|---|
| Sarah & Liam | BRCA1 | 17 | Breast cancer | Breast cancer type 1 susceptibility protein | NP_009225.1 | Helps repair DNA breaks; tumor suppressor |
- How to trace a disease back to a specific gene and mutation.
- How a single mutation can lead to major disruptions in protein function.
- That genotype (mutation) leads to phenotype (symptoms) through faulty proteins.
- How modes of inheritance impact who gets the disease and how it runs in families.
- How bioinformatics tools (OMIM, NCBI) empower researchers to investigate diseases in silico.
- Navigating genomic and protein databases (NCBI, OMIM).
- Understanding and classifying mutation types.
- Connecting gene mutations → protein dysfunction → symptoms.
- Organizing data about gene size, symptoms, life expectancy, and inheritance.
- Thinking critically about genetic research and human health.
- Were you surprised by the inheritance pattern of the disease you studied?
- How might a small mutation cause life-altering or fatal effects?
- Can bioinformatics help identify targets for therapy in genetic disorders?
- What challenges did you encounter when navigating OMIM or NCBI, and how did you overcome them?
