Estimating Risk of Inherited Disease Flashcards
What is fitness?
Relative ability of organism to survive (long enough) to pass on their genes
What can affect fitness?
Alleles
What are the 3 different kinds of alleles that can affect fitness?
Neutral allele (not at all in most cases)
Deleterious allele (sometimes decreases)
Advantageous allele (rarely decreases)
What is an allele?
A variant form of a gene
What is just an important as alleles for the fitness of human beings?
A child being brought up by family members and society
What is selective pressure?
Any phenomena which alters the behaiviour and fitness of living organisms within a given environment
What happens if selective pressure changes?
Importance of different alleles may change
What are the different kinds of genes that can become mutates?
Recessive genes
Dominant and X linked genes
What are some of the few noticable disease of recessive genes?
Sickle cell disease
Thalassaemia
When do recessive genes affect carriers?
When it is associated with selective pressure, such as malaria resistance
What is a de novo mutation?
A genetic alteration that is present for the first time in one family member as a result of a mutation
What are de novo mutations common in?
Dominant disorder, especially where the disease reduces reproductive fitness
How are genotype frequencies worked out?
People: 800AA + 190Aa + 10aa
AA = 800/1000 = 0.8
Aa = 190/1000 = 0.19
aa = 10/1000 = 0.01
How is the allele frequency worked out?
People: 800AA + 190Aa + 10aa
Alleles: 1600A + (190A + 190a) + 20a = 2000 in total
Frequency of A (p) = (1600 + 190) / 2000 = 0.9
Frequency of a (q) = (190 + 20) / 2000 = 0.1
What will p + q always equal?
1
What expression describes first generation genotype and allele frequencies?
Genotype: AA:Aa:aa = p2:2pq:q2
Allele: A:a = p:q
What can you say about relavent frequencies through generations?
Remain constant
What does the Hardy-Weinberg Equilbrium (HWE) state?
Allele frequencies remain constant generation to generation and so do relative proportions of genotype frequency
What are the assumptions underlying the Hardy-Weinberg Equilbrium?
Mutations 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 do mutations increase the proportion of?
New alleles
What does introduction of new alleles as a result of migration lead to?
New gene frequency
What does non-random mating lead to?
Increase in mutant alleles, increasing the proporation of affected homozygotes
What are the 2 kinds of non-random mating?
Assortive mating (choosing new partners due to shared characteristics)
Consanguinity mating (marriage between close blood relatives)
What is assortive mating?
Choosing of partners due to shared characteristics
What is consanguinity mating?
Marriage between close blood relatives
What are homozygotes?
Individual having two identical alleles of a particular gene
What are heterozygotes?
Individual having two different alleles of a particular gene
What is the founder effect?
Loss of genetic variation that occurs when a new population is established by a very small number of individuals from a larger population
What are the different kinds of natural selection?
Positive selection
Negative selection
What does negative selection do?
Reduces reproductive fitness
Decreases prevalence
Leads to gradual reduction of mutant alleles
What does positive selection lead to?
Increase reproductive fitness
Increases prevalence of adaptive traits
Heterozygote advantage
What can a small population size lead to?
Genetic drift
Founder effect
What is natural selection?
Gradual process by which biological trates become either more or less common in a population
What are some heterozygote advantages?
Sickle celll anaemia against malaria
Thalassaemia against malaria
Tay Sachs against TB
Cystic fibrosis against cholera
What is genetic drift?
Random fluctuations in one allele transmitted to high proportion of offspring by chance
What are some examples of the founders effect?
Cystic fibrosis in the faroes
Diminant BRCA1 and BRCA2 in Poland
What are some applications of the Hardy-Weinberg Equilbrium (HWE)?
Useful for calculating genetic risk in genetic counselling
Useful for planning population based carrier screening programmes
