Lecture 13 Flashcards
Continuous traits are a result of multifacorial inheritance. What does this mean?
- Many genes/loci are involved
- Variance is introduced by the environment
- Variance introduced by the genetic backgrounds (epistasis)
Epistasis:
The interaction of genes that are non alleles, such as the suppression of one gene by another
- Genetic and environmental interactions
Quantitative genetics as opposed to traditional mendelian genetics:
- Explain the genetic basis of continuous complex/multifactorial/quantitative traits
- Make no assumptions
- Focus on a populations
- Statistical and mathematical
Genetic architechture:
- How much variation is genetically based
- How many genes are involved
- Where are the genes found in the genome
- What are the genes underlying the QTLs?
How much variation is explained by genetic factors?
- Observe a phenotype to infer genetic causes (forward genetics)
- Focuses primarily on the genes inducing variation on those fundamental to a function
Reverse genetics:
- Create genetic perturbation (mutations, insertions, transpositions) and observes the effects of these changes
- Decompose into linear effects
- Decomposing data into additive (alpha) and dominance (delta) effects
- The effects are linear and therefore independent from each other
- Variation calculation:
- alpha of the AA genotype and the + alpha of the BB genotype and compute a residual/environmental variance sigma squared based e of what is left unexplained
Heritability:
H squared = sigma squared to the base G/ sigma squared to the base P
The fundamental components of measuring how much variation is explained genetically
- The population size and properties
- Accurate measure of the mean/means for the different genetic classes
- A good estimation of the variance for its different componenets
How many loci are involved?
- Observe the covariance between parents and offspring
- Interactive QTL mapping is a straightforward frame work
- Use the change of variance between parents and offspring
- Assume that all the effects are of equal size and all the effects from one parent go in the same direction
- Mean of the parents minus the mean of the other parent
- The rate of convergence to the parents value is proportional to the number of QTL affecting the trait (if many genes are involved the segregating offspring it will take more time to return to the parent)
- Using molecular markers, a step-wise inclusion of WTL to the model:
- Describes the iterative procedure of the WTL mapping strategy
- Find the first significant alpha and include the sum of G
QTL are classified into major, minor QTL and infinitesimal/polygenic effects (infinite number of very small effects)
- We will never have the ability to measure these tiny tiny infinite effects
The power to detect QTL depends on:
- sample size (to gain precise estimate of the variance components)
- the size of the effect/penetrance of the genetic effect
Where are they located in the genome?
- Molecular marker evolution is so useful
- F2 derived from pure inbred lines:
- Use two contrasting parents for the trait of interest
- Cross the 2 parents to generate recombinations
- With only one generation, little recombination so resolution is quite low
- Advancing the resolution of QTL mapping near isogenic lines
- Testing a specific allele in a fixed and homogenous background
- One one allele combination is tested
- Development time is long
- Advancing the resolution of QTL mapping near recombinant inbred lines (RILs)
- More recombinations increase the resolution of the mapping
- All heterozygosity will be wiped out
Advancing the resolution of WTL mapping with advanced intercross RILs (AI-RILs)
- Denser patterns
- Adding some generations to generate cross populations
Advancing the resolution of QTL mapping with Heterozygous inbred families (HIFs)
- Use the residual heterozygosity to learn about the QTL effect (additive vs. dominance)
Advancing the resolution of QTL mapping with multi-parent advanced intercross lines
- Testing multiple alleles in multiple genetic backgrounds
- Cross many lines, inter-mate for many generations, end up with all founder genomes in equal proportions
- Multiple alleles supposes to increase population size to observe a given allele multiple times
- Multiple background implies increasing the noise of co-varying/co segregating loci
- Association mapping:
- ## Trying to map genotype with gene sequence through phenotype measure, gene sequencing and genome-wide markers
High resolution in QTL mapping is achieved by:
- Maximising the number of recombinations present in the populations
- Define small testable intervals
- Homogenise/reshuffle the genetic background to avoiding confounding
Identifying the genes within the QTL:
- Positional cloning
Positional cloning:
- BAC-based physical anchoring
- Used to develop physical maps (as opposed to genetic maps)
- Take the two flanking markers and find the detail within the clones (Marker, BAC clones, Canditate genes on physical map, find some markers with phenotype
Physical maps are used to:
Anchor genetic markers and increase fine-mapping resolution by deriving new markers within WTL interval of interest
Positional cloning using microsynteny-based comparative mapping
- Take the genetic map and blast against a well characterised genome
- Find three regions for marker projection
- New markers can be identified on the blast genome
- Project back onto the other chromosome
Synteny:
- The physical co-localisation of genetic loci on the same chromosome within an individual or species
- It describes the conservation of the order of loci across taxa
