Genetic Risk Calculation

• The importance of genetic pedigrees

  • patterns of inheritance can be more easily visualised in a pedigree
  • related symptoms among family members may refine the diagnosis
  • calculate risk in other family members and future pregnancies
  • helps to inform testing, surveillance, management and treatment in other family members
  • provides a record which can be updated with new information
• Punnet squares

  • used to predict the genotype of a couple's offspring
  • normal allele = A (dominant)
  • mutant allele = a (recessive)
  • unaffective individual = AA
  • Carrier individual = Aa
  • Affected individual = aa
• Calculating risk to unborn children in autosomal recessive disease

  • risk to child = mother carrier risk x father carrier risk x 1/4
• Carrier risk of an autosomal recessive condition if there is no family history

  • at population risk of being a carrier
  • different populations = different risk
  • in genetic counselling we sometimes need to know the actual number - can change risk of unborn child being affected
  • difficult to count carriers in a population as unaffected however Hardy Weinberg equation can be used to calculate carrier frequency if incidence is known
• Hardy Weinberg

  • p + q = 1
  • p^2 + 2pq + q^2 = 1
  • p = normal allele, q = mutant allele
  • p^2 = homozygous normal frequency
  • q^2 = homozygous mutant frequency
  • 2pq = heterozygous frequency
• • sometimes carrier risk from a pedigree can be reduced further if additional information is available
  • genetic test results
  • number of unaffected/affected offspring
  • biochemical test
  • involves a calculation which modifies the initial probability of a person being a carrier by incorporating additional information
• • A simple test (CFTR-OLA) is available that can test for 90% of CFTR mutations in the Northern European population
  • 31 CFTR mutations tested for
  • test reduces CF carrier risk from 1 in 25 (population risk) to 1 in 241