Genetic Risk Assessment

Question 1

Estimation of recurrence risk usually takes into account what 3 things?

Answer 1

1. The diagnosis and is mode of inheritance
2. Analysis of the family pedigree
3. Results of tests that can include linkage studies using DNA markers, but also include clinical data from standard investigation

Question 2

What is meant by the probability of an outcome?

Answer 2

The proportion of times it occurs in a large series of events.

Question 3

What is the law addition?

Answer 3

If events are mutually exclusive, then the probability that either one or the other will occur equals the sum of their individual probabilities.

Example: The probability a pregnant woman will have a boy or a girl is equal to 1/2 + 1/2

Question 4

What is the law of mulitplication

Answer 4

If two or more events or outcomes are independent, then the probability that both the first and the second will occur equals the product of their individual probabilities

Example: The probability a woman pregnant with twins has both a boy and a girl is 1/2 * 1/2

Question 5

What is the difference between reduced penetrance and non-penetrance?

Answer 5

Reduced penetrance refers to the way a disease affects a population. non-penetrance refers to the way a disease affects an individual

Question 6

How do you calculate risk for an autosomal dominant disease?

Answer 6

The risk will be 1/2 * the proportion of heterozygotes who are affected (reduced penetrance)

Example: If a disease has a penetrance of P=0.8, the risk for a child will be 1/2 * 0.8 = 0.4

Question 7

True or False: If a child has an autosomal recessive disease it is assumed both of the affected child’s parents are carriers.

Answer 7

True

Question 8

What is the reisk that a child of parents who are carriers of an autosomal recessive disease will be affected?

Answer 8

1 in 4

Question 9

What is the risk that a healthy child of parents who carriers will be a carrier, too?

Answer 9

2 in 3

Question 10

In sex linked recessive inheritance, what is the probability that an affected father and an unaffected mother will have an affected son?

Answer 10

0. Father’s do not pass their X chromosomes to sons

Question 11

In sex linked recessive inheritance what is the probability that a carrier mother has a carrier daughter? What about an affected son?

Answer 11

There is a 1/2 chance the daughter of a carrier mother will be a carrier and a 1/2 chance the son of a carrier mother will be affected

Question 12

In sex linked recessive disorders, what are the 3 possibilities for why a woman with only one affected son and no positive family history may happen?

Answer 12

1. The woman is a carrier of the mutant allele, and there is now a 1/2 chance that any future son will be affected.
2. The disorder arose in the son because of a new mutation that occured during meiosis in the gamete that led to his conception. The recurrence risk in this situation is negligible
3. The woman is gonadal mosaic, and the recurrence risk will be equal to the proportion of the ova that carry the mutant allele (between 0%-50%)