FinalReviewElementsGeneticsFall2024UPDATED

Final Exam Overview

The final exam focuses on Module 4 material and is designed to be both comprehensive and detailed, rather than cumulative, so students should concentrate on understanding the specific topics covered in this module.

Key Topics

• Mutations: Understanding the types and consequences of mutations is essential; they are critical in the development of cancer, particularly concerning tumor suppressors and proto-oncogenes.

• Gene Networks: Delve into the complexities of gene interactions and regulatory mechanisms that influence cancer progression.

• Hardy-Weinberg Equilibrium: Grasp the principles of population genetics and apply them to solve genetics problems involving allele frequencies.

• Genetic Drift: Study how genetic drift operates, especially in small populations, and understand its implications on allele frequencies over generations.

• Cancer Genetics: Explore the genetic basis of cancer, including specific genes involved in various types of cancer and their roles in cell cycle regulation and tumorigenesis.

Mutations and Alleles

• Understanding Mutations: Mutations can be classified as point mutations, insertions, deletions, or larger chromosomal alterations. Their impact on tumor suppressors, which normally function as brakes on cell division, and proto-oncogenes, which promote cell division, must be understood in context with cancer formation.

• Tumor Suppressors: Key players include genes like p53, which halt the cell cycle and allow for DNA repair, preventing cells from becoming cancerous. Loss of function in these genes can lead to the uncontrolled proliferation characteristic of cancer.

• Proto-oncogenes: These genes promote cell division; however, mutations can convert them into oncogenes, leading to excessive growth and tumor development.

Gene Networks and the Role of p53

• p53 Gene: This gene acts as a master regulatory agent in cell response to stress and DNA damage. Its roles include:

  • Activating apoptosis in damaged cells to prevent tumor formation (e.g., via caspase 10).

  • Initiating DNA repair pathways (e.g., activating BRCA1).

  • Pausing cell cycle progression to allow for repair or apoptosis, thereby inhibiting proto-oncogenes.

Key Oncogenes

• RAS: A family of genes that, when mutated, can lead to the production of proteins that promote cell division and growth. Mutations in RAS proteins (e.g., KRAS, HRAS, NRAS) are common in various cancers and contribute to tumorigenesis by activating signaling pathways like the MAPK pathway.

• ABL: A gene that encodes a tyrosine kinase, which is involved in signaling pathways regulating cell growth and differentiation. This gene becomes oncogenic when fused with the BCR gene (BCR-ABL fusion) in chronic myeloid leukemia (CML), leading to uncontrolled cell proliferation.

• EGF Receptor (EGFR): A growth factor receptor that, when activated by its ligand, stimulates the proliferation and survival of cells. Mutations or overexpression of EGFR are found in many cancers, making it a target for specific therapeutic interventions.

• E2F: A group of genes that are important transcription factors in the regulation of the cell cycle. E2F is regulated by Retinoblastoma (Rb) protein; when Rb is phosphorylated, E2F is released and activates genes necessary for S phase entry and progression, promoting cell division.

• Retinoblastoma (Rb): A critical tumor suppressor protein that regulates the cell cycle. Rb inhibits the E2F transcription factor, preventing the cell from prematurely entering the S phase and thus controlling cell proliferation. Loss of Rb function is associated with various cancers, including retinoblastoma, a rare eye cancer in children.

Hardy-Weinberg Equilibrium

• Key Equations: Understand the mathematical framework of population genetics which includes:

  • p + q = 1: where p is the frequency of one allele and q is the frequency of the alternate allele.

  • p² = frequency of homozygous dominant, q² = frequency of homozygous recessive, and 2pq = frequency of heterozygotes.

• Example Calculations: Be prepared to apply these calculations to practical scenarios, such as determining allele frequencies for autosomal recessive disorders using observed data.

Genetic Drift and Probability of Fixation

• Genetic Drift: This phenomenon starkly affects small populations, leading to random changes in allele frequencies.

• Key Equations:

  • Probability of fixation = 1/(2n) (where n is the population size).

  • Time to fixation = 4n generations.

• Founder Effect: Provides insight into how small, isolated populations undergo unique genetic changes, often leading to high frequencies of certain alleles.

Cancer Genetics

• Definition of Cancer: At its core, cancer is characterized by the uncontrolled division of cells, initiated by one rogue cell that bypasses normal regulatory mechanisms.

• Stages of Cancer:

  • Benign Tumors: Remain localized and are often encapsulated, posing less risk to health.

  • Malignant Tumors: Invade surrounding tissues and can metastasize to other parts of the body, therefore increasing severity.

  • Metastatic Cancer: Involves cancer cells breaking away from primary tumors and establishing secondary tumors at distant sites.

• Familial vs. Sporadic Cancers: Familial cancers arise from inherited genetic mutations and often manifest at a younger age, while sporadic cancers develop later and typically lack a family history.

Specific Genes and Conditions

• Tumor Suppressor Genes: Such as BRCA1, APC, and p53, when lost or mutated, have been linked to specific cancer types.

• Proto-oncogenes: Like ABL and RAS, can transition into oncogenes through various mutations, driving cancer progression.

• BRCA1: A tumor suppressor gene involved in DNA repair mechanisms. Mutations in BRCA1 are strongly associated with breast and ovarian cancer due to its role in maintaining genomic stability.

• APC: The adenomatous polyposis coli gene, another tumor suppressor that regulates cell growth and adhesion. Mutations in APC lead to familial adenomatous polyposis (FAP), a condition characterized by the development of multiple colorectal polyps that have a high risk of malignant transformation.

• Caspase-10: A member of the cysteine-aspartic protease (caspase) family involved in the apoptosis pathway. Its activation leads to apoptosis in response to various signals, contributing to the regulation of cell death in cancer prevention.

• Epigenetic Factors: Influences such as DNA methylation can silence critical genes in tumor suppression, impacting overall gene expression patterns involved in cancer.

Treatment Strategies

• CRISPR Technology: Emerging as a powerful tool for genome editing, it holds promise for targeting and eliminating cancer cells specifically. However, challenges such as differentiating normal from cancer cells remain a significant hurdle.

• Marker-Specific Targeting: Advances in identifying unique markers on cancer cells (e.g., NY ESO) have shown potential for improving treatment outcomes and reducing side effects.

Problem-Solving Strategies for the Exam

• Resources: Utilize provided PowerPoints and any embedded questions within study materials to guide your preparation.

• Keyword Focus: Pay attention to keywords in exam questions that indicate specific types of mutations, genetic principles, or cellular processes.

• Genomic Loci: Familiarity with key genomic loci and their functions is crucial in addressing application-based questions effectively.

Closing Remarks

• Final Preparations: Thoroughly review original PowerPoints and class materials. Engage with peers or instructors to clarify any uncertainties regarding the material covered before the exam.