Estimating Risk of Inherited Genetic Disease Flashcards
Define fitness
The relative ability of organisms to survive and pass on genes
How can alleles affect fitness
In most cases not at all (natural allele) Sometimes decrease (deleterious allele) Rarely increase (advantageous allele)
What is population genetics
The frequency of alleles in the whole population affects the health of the population
How many alleles does a gene have
2
If 800 people have the genotype AA, 190 Aa and 10 aa out of the population of 1000. Calculate the genotype frequency of each
AA - 800/1000 = 0.8
Aa - 190/1000 = 0.19
aa - 10/1000 = 0.01
Calculate the allele frequency of 800 people with the genotype AA, 190 Aa and 10 aa out of the population of 1000
Alleles: 1600 A + (190 A + 190 a) + 20 a = 2000
Frequency of A (p) = (1600 + 190)/2000 = 0.9
frequency of a (q) = (190 + 20)/2000 = 0.1
p+q = 1.0
Overall how can genotype frequencies be calculated
AA:Aa:aa = p^2:2pq:q^2
Overall how can allele frequencies be calculated
A:a
= 2p^2+2pq:2pq+2q^2
= p(p+q) : q(p+q)
= p:q
What happens to allele frequencies from generation to generation
Remain constant
What happens to the relative proportion of genotype frequencies from generation to generation
Remain constant
How was the consistency of allele and genotype frequencies determined
Hardy-Weinberg equilibrium (HWE)
What would be required for the Hardy-Weinberg equilibrium (HWE) to occur
There must be an ideal population where: Mutation can be ignored Migration is negligible (no gene flow) Mating is random There is no selective pressure Population size is large Allele frequencies are equal in the sexes
What increases the proportion of new alleles
Mutations
How can new alleles be introduced
As a result of migration
Intermarriage which leads to a new gene frequency in a hybrid population
What does non-random mating lead to
An increase in mutant alleles therefore increasing the proportion of affected homozygotes
What is assortative mating
Choosing partners due to shared characteristics
What is consangunity
Marriage between close blood relatives
What is natural selection
A gradual process where biological traits become either increase or decrease in a population
What will negative selection do
Reduce reproductive fitness
Decrease the prevalence of traits
Leads to the gradual reduction of mutant alleles
What will positive selection do
Increase reproductive fitness
Increase the prevalence of adaptive traits
Provide heterozygote advantage
Who does sickle cell anaemia mainly affect and what does it provide resistance to
Tropical Africa
Malaria
Who does thalassaemia mainly affect and what does it provide resistance to
SE Asia/Mediterranean
Malaria
Who does glucose-6-phosphate dehydrogenase deficiency (G6PD) mainly affect and what does it provide resistance to
Mediterranean
Malaria
Who does cystic fibrosis mainly affect and what does it provide resistance to
Western Europe
Cholera/Typhoid
Who does congenital adrenal hyperplasisa (CAH) mainly affect and what does it provide resistance to
Yupik Eskimos
Influenza B
Who does GM2 gangliosidosis (Tay-sachs) mainly affect and what does it provide resistance to
E. European Jews
TB
What is the benefit of a large population
It can balance out fluctuations
What can a small population size exhibit
Genetic drift
Founder effect
What is genetic drift
A random fluctuation of one allele transmitted to a high proportion of offspring by chance
What is the founder effect
The reduction in genetic variation which results when a small subset of a large population is used to establish a new colony
How can genetic drift occur
There is a statistical drift of gene frequencies due to chance or random events rather than natural selection in the formation of successive generations
How can the founder effect occur
Genetic drift will occur in the original population to produce a bottleneck effect that reduces genetic diversity
As repopulation begins to occur, a new colony will be started by a few members of the original population (founder effect) to produce limited genetic variation
When is the HWE useful
When calculating risk in genetic counselling
For planning population based carrier screening programmes
What is fitness
The relative ability of organisms to survive (long enough) to pass on their genes
What type of alleles are there
Natural
Deleterious
Advantagous
Which alleles can affect fitness
Deleterious - Sometimes decrease
Advantageous - Rarely increase
What can change the importance of different alleles
Selective pressures
This is known as population genetics
How can mutations in dominant and X-linked conditions occur
Inheritance
De novo
What is a de novo mutation
An alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell (egg or sperm) of one of the parents or in the fertilized egg itself
