Genetic risk calculations

Question 1

Cystic fibrosis

Answer 1

commonest autosomal recessive disease affecting caucasians
incidence 1/2500
250 babies/ year
carrier frequency is 1/25
mutation of the CFTR
main defects in the lungs and pancreas caused by thickened mucus

Question 2

sickle cell disease

Answer 2

incidence 1/1900
abnormal haemoglobin causing sickling of RBCs
haemolytic anemia, abnormal cells block small vessels, shortened life span

Question 3

pedigree symbol for deceased

Answer 3

diagonal line through shape

Question 4

pedigree symbol for divorced/ separated

Answer 4

double small lines across marriage line

Question 5

pedigree symbol for when partners are blood relatives

Answer 5

double line between 2 people

Question 6

what is it called when partners are blood relatives

Answer 6

consanguineous

Question 7

pedigree symbol for twins

Answer 7

2 diagonal lines

Question 8

pedigree symbol for unknown sex children

Answer 8

diamond with number inside

Question 9

pedigree symbol for miscarriage

Answer 9

triangle/ small square or circle

Question 10

how to calculate risk to unborn child of autosomal recessive disease ?

Answer 10

mother carrier risk x father carrier risk x 1/4

Question 11

working out carrier risk

Answer 11

probability of being a carrier halves for each degree of relationship away from the known carrier in a family

Question 12

what is a first degree relative?

Answer 12

a parent, sibling or child

Question 13

what is a second degree relative ?

Answer 13

uncle, aunt, nephew, niece, grandparent, grandchild or half-sibling

Question 14

carrier risk of an autosomal condition if there is no family history

Answer 14

population risk of being a carrier
different populations = different risk
Difficult to count carriers in a population as they are unaffected.
Can be calculated using hardy weinberg equation of the incidence is known

Question 15

what are the hardy weinberg equations?

Answer 15

p+q = 1

p2 + 2pq + q2 = 1

Question 16

what does p and p2 represent in hardy weinberg equations?

Answer 16

normal allele

p2 = homozygous normal frequency, unaffected, not a carrier

Question 17

what does q and q2 represent in hardy weinberg equations?

Answer 17

mutant allele

homozygous mutant frequency - affected

Question 18

what does 2pq represent in hardy weinberg equations?

Answer 18

heterozygous frequency - carriers

Question 19

using additional information to modify risk

Answer 19

sometimes carrier risk from a pedigree can be reduced further in additional information is available, such as genetic test results, number of unaffected/affected offspring or a biochemical test.
Involves a calculation which modifies the initial probability of a person being a carrier by incorporating additional information

Question 20

Reducing CF carrier risk using a genetic test

Answer 20

simple test - CFTR-OLA can test for 90% of CFTR mutations in the Northern European population
reduced CF carrier risk from 1/25 to 1/241

Question 21

what can pedigrees show?

Answer 21

genotype or phenotype as genotype are not always available

Question 22

what is a Punnet square used for?

Answer 22

used to predict the genotype of a couple’s offspring
if someone is clinically unaffected this can be ruled out of the options so there are 3 possible remaining genotypes so the result will be out of 3