Model Answer
0 min readIntroduction
Inherited diseases, also known as genetic disorders, arise from mutations in an individual’s DNA, leading to dysfunctional proteins and subsequent physiological abnormalities. These disorders can be caused by mutations in single genes (monogenic) or complex interactions of multiple genes and environmental factors (polygenic). Understanding the molecular basis of these diseases is crucial for diagnosis, treatment, and potential gene therapy interventions. This answer will detail the molecular underpinnings of Cystic Fibrosis, Sickle Cell Anemia, and Huntington’s Chorea, outlining their genetic causes and resulting human manifestations.
Cystic Fibrosis (CF)
Cystic Fibrosis is an autosomal recessive genetic disorder affecting primarily the lungs, pancreas, liver, intestines, sinuses, and sex organs. It is caused by mutations in the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene located on chromosome 7.
- Molecular Basis: The most common mutation is a deletion of three nucleotides (ΔF508) resulting in the loss of a phenylalanine amino acid at position 508 of the CFTR protein. This leads to misfolding and degradation of the CFTR protein, preventing it from reaching the cell surface.
- Protein Defect: CFTR is a chloride channel responsible for regulating the movement of chloride ions across cell membranes. Its dysfunction disrupts the normal balance of salt and water, leading to the production of thick, sticky mucus.
- Manifestations: This thick mucus obstructs airways in the lungs, leading to chronic lung infections and difficulty breathing. It also blocks ducts in the pancreas, impairing digestion and nutrient absorption. Other symptoms include salty-tasting skin, sinus infections, and male infertility.
Sickle Cell Anemia
Sickle Cell Anemia is an autosomal recessive genetic disorder primarily affecting red blood cells. It is caused by a mutation in the HBB gene, which provides instructions for making beta-globin, a component of hemoglobin.
- Molecular Basis: A single nucleotide substitution (point mutation) in the HBB gene causes a change in the sixth amino acid of the beta-globin chain from glutamic acid to valine (HbS).
- Protein Defect: This altered hemoglobin (HbS) polymerizes under low oxygen conditions, forming long, rigid fibers within red blood cells.
- Manifestations: These fibers distort the red blood cells into a sickle shape, making them fragile and prone to rupture. Sickled cells block small blood vessels, causing pain crises, organ damage, and anemia. Individuals with sickle cell trait (heterozygous) usually experience milder symptoms.
Huntington’s Chorea
Huntington’s Chorea (Huntington’s Disease) is an autosomal dominant neurodegenerative genetic disorder affecting the brain. It is caused by an expansion of a CAG repeat within the HTT gene located on chromosome 4.
- Molecular Basis: The HTT gene contains a CAG repeat sequence. In healthy individuals, this repeat is present 10-35 times. In individuals with Huntington’s Disease, the repeat is expanded to 36 or more times.
- Protein Defect: The expanded CAG repeat leads to the production of a mutant huntingtin protein with an abnormally long polyglutamine tract. This mutant protein aggregates in brain cells, particularly in the striatum, causing neuronal dysfunction and death.
- Manifestations: Symptoms typically appear in adulthood and include involuntary movements (chorea), cognitive decline, and psychiatric disturbances. The disease is progressive and ultimately fatal.
| Disease | Gene Affected | Mutation Type | Inheritance Pattern | Primary Manifestations |
|---|---|---|---|---|
| Cystic Fibrosis | CFTR | Deletion (ΔF508) | Autosomal Recessive | Lung infections, pancreatic insufficiency |
| Sickle Cell Anemia | HBB | Point Mutation | Autosomal Recessive | Anemia, pain crises, organ damage |
| Huntington’s Chorea | HTT | CAG Repeat Expansion | Autosomal Dominant | Involuntary movements, cognitive decline |
Conclusion
In conclusion, Cystic Fibrosis, Sickle Cell Anemia, and Huntington’s Chorea represent distinct examples of how genetic mutations can lead to significant human disease. While each disorder arises from a different molecular defect – a chloride channel dysfunction, an abnormal hemoglobin, and a protein aggregation, respectively – they all underscore the profound impact of our genetic makeup on health and well-being. Advances in genetic testing and gene therapy offer hope for improved diagnosis and potential treatments for these debilitating conditions in the future.
Answer Length
This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.