The following pedigree diagram shows the inheritance of a rare genetic disorder in a family (filled shapes depict affected individuals). Which one of the following is the most likely pattern of inheritance of the disorder?
Show Hint
X-linked Dominant Gold Standard Rule:
An affected father ($X^D Y$) will pass the trait to 100% of his daughters and 0% of his sons.
If you see this clean pattern repeated across generations, choose X-linked dominant immediately!
Step 1: Understanding the Question:
This question asks us to analyze a family pedigree to determine the most probable mode of inheritance for a rare genetic disorder. Step 2: Key Formula or Approach:
To determine the inheritance pattern from a pedigree chart:
1. Check if the disease skips generations (indicative of recessive) or appears in every generation (indicative of dominant).
2. Look at the ratio of affected males to females.
3. Check the specific transmission patterns from affected parents (especially affected fathers to their sons and daughters). Step 3: Detailed Explanation:
Let's analyze the pedigree step-by-step:
• Dominant vs. Recessive:
- The disease does not skip generations; it is expressed in every single generation, which strongly points to a dominant trait.
• Eliminating Y-linked:
- There are multiple affected females (filled circles) in the pedigree. Y-linked traits can only affect males. Thus, Y-linked inheritance is ruled out.
• Eliminating Mitochondrial (Maternal) inheritance:
- In mitochondrial inheritance, an affected mother passes the trait to all her children, while an affected father passes it to none of his children.
- In Generation I, we see an affected father (filled square) and an unaffected mother (empty circle) who have affected children in Generation II. This immediately rules out mitochondrial inheritance.
• Testing X-linked dominant:
- An affected male has the genotype $X^D Y$.
- He must pass his Y chromosome to all his sons (making them normal, $X^d Y$, since they get the normal $X^d$ from their unaffected mother).
- He must pass his $X^D$ chromosome to all his daughters, making 100% of his daughters affected ($X^D X^d$).
- Let's trace the offspring of affected males in the pedigree:
- The affected father in Gen I has daughters in Gen II, all of whom are affected, and his son in Gen II is unaffected.
- In Gen II, the affected male (filled square) is married to an unaffected female. Their children in Gen III consist of affected daughters (filled circles) and unaffected sons (empty squares). No sons are affected, and all daughters are affected.
- In Gen III, another affected male (filled square) married to an unaffected female also passes the trait to all his daughters and none of his sons in Gen IV.
- This perfect paternal-maternal transmission pattern is a definitive hallmark of X-linked dominant inheritance. Step 4: Final Answer:
The pedigree perfectly fits the rules of X-linked dominant inheritance, corresponding to option (A).
