Application of Genetic Principles

Question 1

If both parents are carriers for an autosomal recessive disease, and they have two children, what is the probability that both children will be affected?

Answer 1

1/4 x 1/4= 1/16 (~6%)

Question 2

If a man has an autosomal dominant disease, what is the probability that his two daughters will both inherit the disease?

Answer 2

25%

Question 3

If both parents are carriers for an autosomal recessive disease, what is the probability to have a child who is either homozygous normal or a heterozygous carrier?

Answer 3

75%

Question 4

A couple have a daughter who is affected with an autosomal recessive disease. What is the chance that their second child will also be affected?

Answer 4

25%

Question 5

A couple have a daughter who is affected with an autosomal recessive disease. What is the chance that their second child will be an affected boy?

Answer 5

1/8 (12.5%)

Question 6

A couple have a daughter who is affected with an autosomal recessive disease. What is the chance that their second child will be either homozygous normal or a heterozygous carrier?

Answer 6

75%

Question 7

A couple have a daughter who is affected with an autosomal recessive disease. If they have three children, what is the chance that all three will be affected?

Answer 7

1/64

Question 8

For an autosomal dominant condition showing penetrance of 75%, the risk that the child of an affected individual will be affected equals?

Answer 8

(1/2)*(3/4)= 3/8 (37.5%)

Question 9

T or F. For an autosomal recessive disorder, both parents are considered heterozygous

Answer 9

T.

Question 10

What is the probability that a healthy sibling of an affected child with an autosomal recessive disease is a carrier?

Answer 10

2/3. 1/3 that they are normal homozygous

Question 11

Consider a family with four children, all of whom are affected with NF1. The children’s mother is similarly affected; the father has no personal or family history of NF1. Given that NF1 is an autosomal dominant disorder, what is the probability that all four children would be affected?

Answer 11

1/16 (6.25%). Each child is an independent probability: 1/2 x 1/2 x 1/2 x 1/2 = 1/16

Question 12

In the family with four NF1 children (previous question), what is the probability that a fifth child would have NF1?

Answer 12

½. For the mating described (Aa x aa), the probability is ½ for each pregnancy.

Question 13

Betty was affected with Marfan syndrome, an autosomal dominant connective tissue disorder. What is the probability that Betty’s great-grandson will inherit her mutation?

Answer 13

1/8. There are three generations (three meioses) between Betty and her great-grandson. For each generation, the risk is 1/2. 1/2 x 1/2 x 1/2 = 1/8

Question 14

Robert’s sister has sickle cell anemia (autosomal recessive). She is the only affected individual in the family. The probability that Robert is a sickle cell carrier is closest to:

Answer 14

2/3 (67%). Both Robert’s parents are obligate carriers, but he is not affected, so his risks are 2/3 to be a carrier and 1/3 to be homozygous normal.

Question 15

Mr. Green and his wife have a child with an autosomal recessive disorder. There are no other affected individuals in the family. The probability that Mr. Green’s healthy brother is a heterozygous carrier for the same disorder is closest to

Answer 15

1/2 (50%). One of Mr. Green’s parents is a carrier for the AR disorder, but since Mr. Green has no affected siblings, it is most likely that only one of his parents is a carrier. Therefore, the best estimate is that Mr. Green’s sibling has a ½ chance to inherit the mutation.

Question 16

George and Margaret are expecting their first child. George’s sister is affected with cystic fibrosis (autosomal recessive). Margaret’s sister has a child affected with cystic fibrosis. No other family members are affected. What is the probability that George and Margaret’s child will be affected with cystic fibrosis?

Answer 16

1/12 (or 0.08). Probability George is a carrier = 2/3 (because both his parents are obligate carriers).
Probability Margaret is carrier = 1/2 (because only one of her parents is an obligate carrier).
Probability of passing mutation to child is 1/2 for EACH parent.
2/3 x 1/2 x 1/2 x 1/2 = 1/12

Question 17

Tom and Mary Miller recently married. Mary has a child from a previous marriage who is affected with cystic fibrosis (autosomal recessive). Tom’s brother also has a child affected with cystic fibrosis. There are no other affected individuals in the family. The probability that a child born to Tom and Mary will be affected with cystic fibrosis is closest to:

Answer 17

1/8 (12.5%). Probability Mary is a carrier = 1
Probability Tom is a carrier = 1/2
Probability a child would inherit mutations from both parents = ½ from each parent = 1/2 x 1/2
Probability for child to be affected = 1 x 1/2 x 1/2 x 1/2 = 1/8

Question 18

Mary’s maternal grandfather was affected with Becker muscular dystrophy (X linked recessive). Mary is currently pregnant with a male fetus. The probability that her son will inherit Becker muscular dystrophy is closest to:

Answer 18

1/4 (25%). Mary’s mother is an obligate carrier.
Probability Mary is a carrier = 1/2.
Probability Mary will pass the mutation to her male fetus = 1/2.
1/2 x 1/2 = 1/4
(Note that the stem says that the fetus is male. Thus, probability of a male is 1 (100%).

Question 19

All but one of the family relationships given below have the same proportion of shared genes. Which option differs from the others?

first cousins
grandparent-grandchild
uncle-niece
half-siblings

Answer 19

First cousins. First cousins share only 1/8 of their genes, on average. For all other options, the expected proportion of shared genes is 1/4

Question 20

The incidence of Tay-Sachs disease in the Ashkenazic Jewish population is 1 in 3600. Stephen and Sarah are both of Ashkenazic Jewish descent and are about to give birth to their first child. Stephen had a brother who died at age two of Tay-Sachs disease. Based on the information given, what is the probability that Stephen and Sarah’s child will be affected with Tay-Sach’s disease?

Answer 20

1/180. Based on family history (affected brother), Stephen’s risk to be a carrier =
2/3. Since no significant family history is provided, Sarah’s risk is the population risk. Using Hardy-Weinberg, q(squared) = 1/3600. q = 1/60. Since p is close to 1, carrier freq ~2q = 1/30.
Their risk to have an affected child = 2/3 x 1/2 x 1/30 x 1/2 = 1/180.

Question 21

Factor V Leiden is a mutation in the factor V gene that predisposes heterozygous individuals to venous thrombosis. The disease phenotype exhibits low penetrance (~10%). Steve carries the factor V Leiden mutation (he is heterozygous), and he has experienced venous thrombosis. Based on the information given, what is the probability that Steve’s son has inherited the mutation AND will experience venous thrombosis?

Answer 21

1/20 (5%). Risk of the son to inherit the factor V Leiden mutation = ½. The empiric risk given for reduced penetrance = 1/10. 1/2 x 1/10 = 1/20. Venous thrombosis is a common disorder, and this is a typical scenario for a common risk allele. 1/20 is significantly higher than the general population risk of ~1/100