Genetic risk calculations Flashcards
Cystic fibrosis
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
sickle cell disease
incidence 1/1900
abnormal haemoglobin causing sickling of RBCs
haemolytic anemia, abnormal cells block small vessels, shortened life span
pedigree symbol for deceased
diagonal line through shape
pedigree symbol for divorced/ separated
double small lines across marriage line
pedigree symbol for when partners are blood relatives
double line between 2 people
what is it called when partners are blood relatives
consanguineous
pedigree symbol for twins
2 diagonal lines
pedigree symbol for unknown sex children
diamond with number inside
pedigree symbol for miscarriage
triangle/ small square or circle
how to calculate risk to unborn child of autosomal recessive disease ?
mother carrier risk x father carrier risk x 1/4
working out carrier risk
probability of being a carrier halves for each degree of relationship away from the known carrier in a family
what is a first degree relative?
a parent, sibling or child
what is a second degree relative ?
uncle, aunt, nephew, niece, grandparent, grandchild or half-sibling
carrier risk of an autosomal condition if there is no family history
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
what are the hardy weinberg equations?
p+q = 1
p2 + 2pq + q2 = 1
what does p and p2 represent in hardy weinberg equations?
normal allele
p2 = homozygous normal frequency, unaffected, not a carrier
what does q and q2 represent in hardy weinberg equations?
mutant allele
homozygous mutant frequency - affected
what does 2pq represent in hardy weinberg equations?
heterozygous frequency - carriers
using additional information to modify risk
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
Reducing CF carrier risk using a genetic test
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
what can pedigrees show?
genotype or phenotype as genotype are not always available
what is a Punnet square used for?
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
