Estimating Risk of Inherited Genetic Disease Flashcards
Define Fitness
The relative ability of organisms to survive (long enough) to pass on their genes.
If an allele reduces reproductive fitness, what is this known as ?
Deleterious allele
If an allele increases reproductive fitness, what is this known as ?
Advantageous allele.
If an allele doesn’t impact reproductive fitness, what is this known as ?
Neutral allele
Name two diseases that are recessive.
Sickle cell disease
Thalassaemia
Where are de novo mutations common?
In dominant disorders especially where disease reduces reproductive fitness
What kind of mutation is responsible for learning difficulty syndromes?
De novo
People : 800 AA + 190 Aa + 10 aa = 1000 total
Work out the genotype frequency for the following-
AA
Aa
aa
AA= 0.8 (800/1000)
Aa= 0.19 (190/1000)
aa=0.01 (10/1000)
People : 800 AA + 190 Aa + 10 aa = 1000 total
Alleles : 1600 A + (190 A + 190 a) + 20 a = 2000
Work out the allele frequency for the following-
A(p)
1600 + 190 = 0.9
————–
2000
People : 800 AA + 190 Aa + 10 aa = 1000 total
Alleles : 1600 A + (190 A + 190 a) + 20 a = 2000
Work out the allele frequency for the following-
A(q)
2000
p=q=>?
1
State the equation for the Hardy Weinburg.
p^2 + 2pq + q^2 = 1
^=squared
P^2=?
p^2 = dominant homozygous frequency (AA)
2pq = ?
2pq = heterozygous frequency (Aa)
q^2 =?
q^2 = recessive homozygous frequency (aa)
Discuss the frequency of allele frequencies
Allele frequencies remain constant generation to generation.
Discuss the relative proportion of genotype frequencies
Relative proportion of genotype frequencies remain constant generation to generation.
What are some of the assumptions made when using the HW equation?
- 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
What increases the proportion of new alleles?
Mutation
What does the introduction of new alleles through migration/intermarriage lead to?
New gene frequency in hybrid population.
What does non-random mating lead to?
An increase mutant alleles, thereby increasing proportion of affected homozygotes
Define Assortative mating
Choosing of partners due to shared characteristics
Deafness & sign language
Define Consanguinity
- Marriage between close blood relatives.
Name two founder effects
->(the reduction in genomic variability that occurs when a small group of individuals becomes separated from a larger population)
Physical or cultural isolation
Describe natural selection.
A gradual process by which biological traits become either more or less common in a population.
Discuss Negative selection
- Reduces reproductive fitness.
- decreases the prevalence of traits.
- leads to gradual reduction of mutant allele.
Discuss positive selection
- Increases reproductive fitness.
- Increases the prevalence of adaptive traits.
- Heterozygote advantage.
What three recessive conditions mean that you are resistant to malaria?
Thalassaemia
Sickle cell anaemia
Glucose-6-phosphate dehydrogenase deficiency (G6PD)
If you have cystic fibrosis, what will you be resistant to?
Cholera/Typhoid
If you have Congenital Adrenal Hyperplasia (CAH) what will you be resistant to?
Influenza B
If you have GM2 gangliosidosis (aka Tay-Sachs) what will you be resistant to?
TB
What can smaller populations have?
Genetic Drift
Founder effect
Define genetic drift.
Random fluctuation of one allele transmitted to high proportion of offspring by chance.
Define founder effect
The reduction in genetic variation that results when a small subset of a large population is used to establish a new colony.
Discuss genetic drift.
Mutations (alleles) are widespread and neutral.
Statistical drift of gene frequencies due to chance or random events rather than natural selection in the formation of successive generations
What does the bottleneck effect do?
Reduces genetic diversity
What is the HW equation useful for?
Useful for calculating risk in genetic counselling
Useful for planning population based carrier screening programmes
