Module D: Risk Calculation & Genetic Services

Question 1

For recessive conditions, how does the carrier risk decrease for each generation separating the consultand from a known carrier?

Answer 1

carrier risk decreases by 1/2 for each generation separating the consultand from a known carrier

Question 2

For recessive conditions, how is combined carrier risk calculated?

Answer 2

carrier risk of two parents are multiplied

Question 3

How can the carrier risk of two parents be used to determine the risk of having an affected child?

Answer 3

carrier risks of two parents are multiplied, and then risk of having affected child is 1/4 of combined carrier risk

Question 4

How can the carrier rate for autosomal recessive disorders be calculated using the Hardy-Weinberg equilibrium?

Answer 4

carrier rate = twice the square root of disease frequency (q²)

Question 5

For X-linked conditions, what is the risk for a mother of being a carrier?

Answer 5

2/3 risk of being a carrier (i.e. a heterozygote), if she has an affected male son and no other male family history of the disease

Question 6

In X-linked conditions, mothers of affected males have a 2/3 risk of being a carrier assuming no other family history of the disease. What accounts for the other 1/3 of risk?

Answer 6

other 1/3 is due to new mutations in the affected son’s X-chromosome

Question 7

For X-linked conditions, how does the carrier risk decrease for each generation separating the consultand from a known carrier?

Answer 7

each generation of women separating a known heterozygote/carrier from the consultand reduces the carrier risk by 1/2

Question 8

How is disease frequency for autosomal dominant disorders obtained for the Hardy-Weinberg equilibrium?

Answer 8

disease frequency is frequency of heterozygotes

Question 9

How is gene frequency for autosomal dominant disorders obtained for the Hardy-Weinberg equilibrium?

Answer 9

gene frequency = 1/2 the frequency of affected individuals

Question 10

For X-linked disorders, how is the gene frequency obtained?

Answer 10

gene frequency = frequency of affected males

Question 11

For X-linked disorders, how is the carrier frequency obtained?

Answer 11

carrier frequency = twice the disease frequency

Question 12

What is the 5% rule? (2)

Answer 12

if disease frequency (q) is less than 5%, then use 1 for the frequency of the normal gene

if population carrier rate is less than 5%, ignore contribution of possible carriers from outside the family (unless affected individual is removed from consultand by >4 generations)

Question 13

What are teratogens?

Answer 13

agents or conditions that can give rise to birth defects

Question 14

What is chorionic villus sampling?

Answer 14

prenatal testing method that retrieves fetal cells from placenta at 10-12 weeks gestation

Question 15

What is amniocentesis?

Answer 15

retrieves fetal cells from amniotic fluid at 14-20 weeks gestation

Question 16

How is fetal DNA retrieved?

Answer 16

from maternal blood

Question 17

How is fetal imaging performed?

Answer 17

by ultrasound or MRI

Question 18

Describe the steps of preimplantation genetic diagnosis.

Answer 18

embryo from in-vitro fertilizaiton allowed to grow to 8-16 cell stage

single cell removed and tested for genetic disorder

only embryos without the disorder are implanted

Question 19

What is dysmorphology?

Answer 19

genetic subspecialty area concerned with syndrome identification for individuals w/ congenital abnormalities

Question 20

A dysmorphology evaluation includes (4)

Answer 20

family hx

pregnancy hx

physical exam

labs/imaging

Question 21

What are the seven most common treatment methods for genetic disorders?

Answer 21

remove toxic substance

enzyme replacement therapy

dietary restriction

supply missing small molecule

transplant

block synthesis of toxic substance

gene therapy

[mnemonic: RED-STBG — think of BA 77W G-STBG]

Question 22

Define empiric risk.

Answer 22

risk estimate based on observation