Bob arrives in your office for genetic counseling. Bob's bro

[Hijeck]

Bob arrives in your office for genetic counseling. Bob's brother Tom died at a young age from Tay-Sachs disease. Both he and his sister Sarah are unaffected. Bob's son Adam and Sarah's daughter Jennifer have recently married and are expecting their first child. What is the chance that the child would have Tay-Sachs disease?
(A) 1/4
(B) 1/9
(C) 1/12
(D) 1/36
(E) 1/44

[Hijeck]

Answer is D


In Ashkenazi Jews in North America, the gene for Tay-Sachs disease is very common. Tay-Sachs disease is a neurologic degenerative disorder that typically develops at approximately 6 months of age. Affected children become progressively blind and regress mentally as well as physically. The disease is usually fatal in early childhood. The cause of the disease results in the mutation of a specific lysosomal enzyme, hexosaminidase A (hex A). In classic Mendelian genetics the unaffected siblings, Bob and Sarah, each have a 2/3 chance of being a carrier for the Tay-Sachs disease and hence a 50% chance of passing on the carrier state. Therefore, both Adam and Jennifer have a 1/3 chance of being a carrier. If both Adam and Jennifer are carriers, there is a 1/4 chance that a child would be affected with the Tay-Sachs disease. Therefore, the cumulative probability is 1/3 x 1/3 x 1/4, which equals 1/36.