Estimating risk of inherited genetic disease

Question 1

Fitness of alleles

Answer 1

• Means the relative ability of organisms to survive and pass on genes

Question 2

3 alleles fitness types

Answer 2

• Neutral allele: most common, not effect
• Deleterious allele: less common, sometimes decrease
• Advantageous allele: rarely increased

Question 3

Population genetics definition

Answer 3

• Frequency of alleles in the whole population affects health of the population

Question 4

Generation genotype frequency

Answer 4

AA:Aa:aa = p^2: 2pq: q^2

Question 5

Generation allele frequency

Answer 5

A:a = p : q

Question 6

Hardy-Weinberg Equilibrium

Answer 6

• Allele frequencies remain constant generation to generation
• p+q = 1
• p+q+r=1

Question 7

Assumptions for an ideal population

Answer 7

• Mutation can be ignored
• Migration is negligible (no gene flow)
• Mating is random
• No selective pressure
• Population size is large
• Allele frequencies are equal in the sexes

Question 8

Gene flow

Answer 8

• Mutations increase the proportion of new alleles

- Introduction of new alleles as a result of migration leads to new gene frequency in hybrid population

Question 9

Non-random mating

Answer 9

• Leads to increase mutant alleles which leads to an increased proportion of homozygotes
• Assortative mating (partners with shared characteristics)
• Consanguinity (marriage between close blood relatives)

Question 10

Natural selection

Answer 10

• Gradual process by which biological traits become more or less common in a population
• Negative selection
• Positive selection

Question 11

Negative selection

Answer 11

• Reduces reproductive fitness
• Decreases the prevalence of traits
• Leads to a gradual reduction of mutant allele

Question 12

Positive selection

Answer 12

• Increases reproductive fitness
• Increases prevalance of adaptive traits
• Heterozygote advantage
• Actively maintained in gene pool at frequencies longer than expected from genetic drift alone

Question 13

Genetic drift

Answer 13

• Random fluctuation of one allele transmitted to high proportion of offspring by change
• Happens due to random events, not natural selection

Question 14

Founder effect

Answer 14

• Reduction in genetic variation when a small subset establishes a new colony
• If a new colony is started by a small group with reduced genetic diversity then there will be limited genetic variation
• e.g. Amish -> Ellis-van Creveld syndrome has assortative mating so they have natal teeth and extra finger

Question 15

Clinical application of HWE

Answer 15

• Calculating risk in genetic counselling

- Planning population based carrier screening programmes