A normal couple has one daughter affected with Cystic fibrosis. They are now planning to have another child. What is the chance of siblings being affected by the disease –
## **Core Concept**
Cystic fibrosis is an autosomal recessive genetic disorder caused by mutations in the **CFTR (cystic fibrosis transmembrane conductance regulator) gene**. This disorder affects the respiratory, digestive, and reproductive systems. For a child to be affected, they must inherit two defective copies of the gene (one from each parent).
## **Why the Correct Answer is Right**
The couple in question has a daughter affected by cystic fibrosis. For their daughter to be affected, both parents must be **carriers** of the disease, meaning they each have one normal and one mutated copy of the **CFTR gene**. Carriers are usually asymptomatic but can pass the mutated gene to their offspring. The chance of each sibling being affected is calculated using a Punnett square, which shows the probability of inheriting two defective copies of the gene (one from each parent) is **25%**.
## **Why Each Wrong Option is Incorrect**
- **Option A:** This option suggests a 0% chance, which would only be true if the parents were not carriers or if the disease were dominant. Given the couple has an affected child, both parents must be carriers.
- **Option B:** This option suggests a 50% chance, which is incorrect because it represents the chance of a child inheriting one mutated copy of the gene (being a carrier like the parents), not two.
- **Option D:** This option suggests a 100% chance, which is clearly incorrect as it does not account for the genetic variability and the fact that not all offspring will inherit two defective copies of the gene.
## **Clinical Pearl / High-Yield Fact**
A key point to remember is that for autosomal recessive diseases like cystic fibrosis, **two carrier parents have a 25% chance with each pregnancy of having an affected child**, a 50% chance of having a child who is a carrier, and a 25% chance of having a child who is neither affected nor a carrier.
## **Correct Answer:** . **25%**