Question

Annette's maternal grandfather died of Huntington's disease when he was 53 and Annette was 8. Huntington's is a rare autosomal dominant degenerative neural disorder that usually hits people in their late forties, early fifties. Annette loved her grandfather very much and was deeply affected by the painful progression of his disease. She wants to get pregnant but does not want to risk giving birth to a child that will suffer as much as her grandfather. If she tested positive for Huntington's, what is the probability of her first child to develop Huntington's? Of her second child? Of her mother? (Note that since Huntington’s is so rare, you can assume that neither grandmother, nor father or partner have the Huntington’s mutation).

Answer 1

Answer and Explanation:

Huntington disease is caused by a mutation in the gene that codifies for the Huntingtin protein (Htt). The mutation produces an altered form of the protein leading to the neuron´s death in certain areas of the brain.

Huntington disease characterizes for being,

• Hereditary, passing from generation to generation. To express the disease, a person must have been born with an altered gene.

• Autosomal, affecting men and women equally, because the mutated gene is located on an autosomal chromosome.

• Dominant, which means that by getting only one copy of the altered gene coming from any of the parents, the receiving person will express the disease. The mutation in the gene dominates over the normal gene copy.

• Expressed by heterozygosis. Most people affected by the disease are heterozygous, with a normal copy and a mutated copy.

An affected heterozygous person has 50% of chances to give a normal recessive allele or an altered dominant allele. When one of the progenitors is a carrier and the other one is a healthy person, the progeny have 50% of probabilities of inheriting a dominant allele expressing the HD from the affected parent.

In the exposed example, Annette probably is heterozygous, Hh, and she marries a healthy man, hh.

Parental) Hh x hh

Gametes) H, h h, h

F1) 1/2 Hh, 1/2 hh

The probability of the first child to develop HD is 50%, or 1/2

The probability of the second child to develop HD is also 50%

The probability of both children to develop HD is 1/2 x 1/2 = 1/4, or 0.25

Now, Annette´s grandpa had the disease, Hh

Annette´s grandma did not, hh

The probability of her mother to develop HD is 50% because she could just inherit the dominant allele from her father.