Quantitative Genetics Flashcards
1
Q
What is a quantitative trait?
- What are the two characteristics of quantitative traits?
A
- A characteristic which is continuous over a range
e. g. human height, weight, colour and many human diseases - many human diseases exist on a normal distribution and are then only detected once they reach a threshold
- What are the two characteristics?
1. Many genes contribute to one trait = polygenic or multigenic inheritance
2. The trait can be affected by the environment
2
Q
How can the number of genes be determined by the multiple gene hypothesis?
A
- From the relative frequency of extreme phenotypes within the population it is possible to estimate the number of genes contributing to the trait
- Can only be done with the quantitative trait has contiguous variation that can be measured and the genes contribute to phenotype in an additive way
e. g. one gene pair affecting trait = 1:2:1 ratio
e. g. two gene pairs affecting trait = 1:4:6:4:1 - Number of different phenotypes = 2 x number of genes +1
3
Q
What is heritability?
A
- The proportion of total phenotypic variation (Vp) in a population that is due to genetic factors
- It is different in different environments
- It is NOT: how much of a trait is genetically determined
e. g. a mean broad sense heritability estimate of 0.65 for human height means that 65% of the overall variation in height can be explained by genotypic differences among individuals
4
Q
How do you calculate phenotypic variance?
A
Vp = phenotypic variance Vg = genotypic variance Ve = environmental variance Vgxe = genotype-environment interaction variance (often ignored)
Vp = Vg + Ve + Vgxe
5
Q
What is broad sense heritability?
A
- Tells us the proportion of variance in a population within a single generation that is due to genetic factors
H^2 = Vg/Vp - Gives an estimate of 0 to 1
- Low heritability: variation is mainly due to environmental effects
- High heritability: variation is mainly due to genotypic effects
- It is not useful for breeding of livestock as it considers all genotypic effects- and some of them e.g. dominant alleles are not transmissible to the next generation in predictable ways
6
Q
What is narrow sense heritability?
A
- Fully additive genetic variance means that the animals/lpants with the desired trait are all homozygotes
- This is because total genetic variance Vg = Va (additive variation) + Vd (dominant variation) + Vi (gene environment interaction variation)
- Narrow sense heritability (h^2) = Va/Vp = Va/Ve + Va + Vd + Vi
- Therefore narrow sense heritability is the proportion of total phenotypic variance due to additive genetic variation
- Used for selective breeding
7
Q
How do you estimate narrow sense heritability using family data?
A
Narrow sense heritability can be seen as a measure of how heritable a trait is
- This is estimated by looking for a correlation between the parents and the offspring
- The mean offspring data is correlated to the midparent (mother + father/2) value
8
Q
How are genes that affect a quantitative trait identified?
A
- Candidate gene (educated guess) approach:
- Most commonly used approach - Quantitative Trait Loci (QTL) mapping:
- Used for model organisms in which genomes can be controlled - GWAS:
- For human traits and disorders
- The genome is scanned for regions that are commonly associated with the disease
9
Q
What are multifactorial disorders?
A
- These disorders display familial clustering with no recognised pattern of Mendelian inheritance
- Many factors are involved in their development- genetic and environmental
- Multifactorial inheritance = polygenic inheritance + environmental factors
10
Q
What is additive genetic variance?
A
- All organisms with the desired trait are homozgyotes
- Ideal for selective breeding
11
Q
What is a polygenic trait?
A
- Phenotype is determined by many genes
- Each gene exerts a small additive (not dominant) effect
- No single gene is dominant or recessive to another (although in reality some genes will have dominant effects
- Examples of polygenic traits: blood pressure, height, intelligence, skin colour as well as disease traits
- Display a normal distribution
12
Q
What is a discontinuous multifactorial trait?
A
- A normally distributed phenotypic trait with a threshold
- Above the threshold the trait is observed
- Plotted on a distribution curve- individuals to the right of the threshold are affected
- In the general population those right of the threshold are the general population incidence
- Among relatives of a affected child the curve becomes a liability curve and is shifted to the right and the proportion beyond the threshold is the familial incidence (higher than the general incidence as they share alleles)
13
Q
What are the experimental approaches to determine genetic susceptibility (inherited predisposition to developing a disease)?
A
- Population/migration studies:
- The genotype remains the same but there can be massive changes in the environment - Twin studies:
- Comparing incidence in identical (MZ) vs non-identical (DZ) twins
- Environment is the same we are looking at different genetic contributions
- The higher the MZ/DZ concordance ratio- the stronger the genetic component - Family studies:
- Comparing recurrence risk in families (how often people within the same family develop the same condition - Adoption studies:
- Different genotype same environment - Mapping studies
14
Q
What are the risk factors for NTDs?
A
- There is a genetic component as recurrence for first degree relatives is 4-5%
- There have been so susceptibility genes identified to date
- The environmental factor: folate has been show to reduce the risk of recurrence by 70-75%
15
Q
What is an odds ratio/relative risk ratio?
A
- Ratio of the risk to relatives of affected individuals compared to the general population incidence
- Rough measure of genetic component of disease (takes into account not only genetic factors but also environmental- really a measure of familial risk rather than heritability)
e.g. Autism:
Recurrence risk of autism in siblings = 6%
Incidence of autism in general population = 0.1%
Therefore:
Relative risk ratio for siblings = 6/0.1 - 60 fold relative risk for siblings in this family
