72. The pedigree given below follows the inheritance pattern of a late-onset (after age of 30 years) genetic disease that is 100% penetrant. Affected individuals are indicated by a solid circle (woman) or solid square (males). RFLP analysis of DNA from each individual is shown below in the pedigree.

Which grandchildren (IIIb to IIId) will be affected by the disease after attaining the age of 30 years?
(1) onlyIIIb
(2) Both IIIb and IIIe
(3) Both IIIc and IIId
(4) Both IIIb and IIId

Problem recap

The pedigree shows two first-generation couples; affected individuals are shaded, onset is after 30 years, and penetrance is 100%. RFLP bands are provided below each individual, letting the disease allele be tracked by co-segregating marker fragments through meiosis. The task is to determine which grandchildren (IIIb, IIIc, IIId, IIIe) will manifest disease after 30.

Core logic

• Because the trait is fully penetrant and late-onset, all carriers of the dominant disease allele will eventually be affected after 30; absence of shading in young individuals does not exclude disease.

• Use the RFLP pattern in the affected parent(s) to identify the marker allele linked to the disease chromosome, then follow that marker into the grandchildren to see who inherited the disease haplotype. Recombination is assumed negligible across the short marker–disease interval for this pedigree question.

Tracking the disease haplotype

• In generation I, the shaded male is affected; his unique marker band (call it “b-band”) marks the disease chromosome. His spouse lacks this band, so the “b-band” segregates with disease into their affected child in generation II.

• In generation II, the affected parent carries the “b-band”; unaffected spouses lack it. Among their children in generation III, those who carry the same “b-band” have inherited the disease chromosome and, being dominant and fully penetrant after 30, will be affected after reaching 30.

Identifying IIIb–IIId from bands

• Grandchild IIIb shows the “b-band” that co-segregates from the affected line, indicating carriage of the disease allele and future affection after 30.

• Grandchild IIIc lacks the “b-band,” indicating inheritance of the normal chromosome; IIIc will remain unaffected.

• Grandchild IIId shows the “b-band,” indicating disease allele inheritance and future affection after 30.

• Grandchild IIIe lacks the linked band and will remain unaffected.

Option-by-option evaluation

• (1) only IIIb: Incorrect, because IIId also carries the disease-linked marker and will be affected after 30.

• (2) Both IIIb and IIIe: Incorrect; IIIe lacks the disease-linked band and should be unaffected.

• (3) Both IIIc and IIId: Incorrect; IIIc lacks the disease-linked band while IIId carries it.

• (4) Both IIIb and IIId: Correct; both carry the disease-linked RFLP band from the affected parent and will develop the late-onset dominant disease after 30.

Note on interpretation: The conclusion relies on full penetrance and linkage of the RFLP marker to the disease allele; under these standard exam assumptions, marker recombination is ignored, so the disease haplotype is tracked unambiguously to IIIb and IIId.