lab 4/21/26Study Notes on Genetic Mutations and Colorectal Cancer

Genetic Conditions and Cancer Risk

• Recessive Conditions
    - Require both recessive alleles to express the condition.

• Dominant Conditions
    - Only require one mutated copy of the allele to increase risk of disease.
    - Example: A mutation can increase the risk of colorectal cancer by 80%.
    - Note: If diagnosed with colorectal cancer at age 20 or 70, it is likely not due to this mutation.
    - Most diagnoses occur around ages 40-45.

Colorectal Cancer Statistics

• Normal Population Risk:
    - Approximately 5% risk of developing colorectal cancer.

• Impact of Mutation:
    - Mutated gene significantly increases risk beyond the normal percentage.

• Testing Recommendations:
    - Individuals with a family history of mutations should consider genetic testing.
    - Those with a mutation should undergo colonoscopy screenings every 1-2 years rather than the standard every 5-7 years starting from age 45.

Understanding Mutations and Genetic Testing

• Electrophoresis:
    - Process used to analyze DNA.
    - Utilizes restrictive enzymes:
      - If the enzyme detects a mutation, it splits the DNA into two fragments.
      - If no mutation is detected, the DNA remains as a whole fragment.

• DNA Characteristics:
    - DNA is slightly negatively charged.
    - During electrophoresis, DNA will move from the negative to the positive side due to this charge.
    - Smaller DNA fragments travel faster than larger ones through the gel.

• Relevance in Cancer Studies:
    - Understanding mutations helps identify risk factors for cancers such as colorectal cancer.

Review of Genetic Concepts

• Proto-oncogenes and Oncogenes:
    - Proto-oncogenes initiate the cell cycle.
    - Mutated proto-oncogenes can become oncogenes, leading to uncontrolled cell growth.

• Tumor Suppressor Genes:
    - Prevent tumor formation by promoting apoptosis (regulated cell death).

• Dominant Condition Clarification:
    - Despite the 80% risk associated with mutations, not everyone with the mutation will necessarily develop cancer due to the presence of a second allele that may be non-mutated.

DNA Fragment Analysis

• Example of DNA Analysis:
    - In forensic investigations, DNA can be split into fragments to match samples.
    - Visualization is like a matching game where samples can be compared with suspects.

• Illustration of Fragmentation:
    - DNA strand from parents has two alleles.
    - If the restrictive enzyme detects a mutation, it splits the DNA into two fragments.

Practical Application in the Lab

• Experimental Setup:
    - Lab includes analyzing DNA samples from individuals related to a family tree for mutations.

• Pedigree Analysis:
    - Affected individuals are indicated by shaded shapes in the family tree.
    - Squares represent males and circles represent females.
    - Lines through shapes indicate deceased individuals.

Family Analysis Example

• Understanding Risks:
    - Example individuals: Stan, Susan, Marshall (mutated), Sarah (normal), Bob (mutation), Warren (older, unlikely to have mutation), Jane (lower risk).
    - Bob's risk estimated at 50% due to family history, while Jane appears to have a slight risk.

Laboratory Procedure for DNA Analysis

• Sample Preparation:
    - Use of gels for DNA separation.
    - Loading DNA samples into wells carefully to avoid damaging the gel.

• Loading Technique:
    - Use a pipette to fill wells, ensuring to not pierce through or place too high.
    - Each group responsible for specific lanes on the gel.

• Electrophoresis Run:
    - Fill gel with buffer solution to allow current flow.
    - Run machine at correct settings for about 35 minutes to separate DNA fragments.

• Post-Electrophoresis:
    - Results observed under blue light, with the option to use screen illustrations if results are not clear.

• Worksheet Submission:
    - Complete and submit worksheets with observations from the experiment.
    - Recommended to use laptops for better accuracy in responses.