Lecture 13

Question 1

Continuous traits are a result of multifacorial inheritance. What does this mean?

Answer 1

• Many genes/loci are involved
• Variance is introduced by the environment
• Variance introduced by the genetic backgrounds (epistasis)

Question 2

Epistasis:

Answer 2

The interaction of genes that are non alleles, such as the suppression of one gene by another
- Genetic and environmental interactions

Question 3

Quantitative genetics as opposed to traditional mendelian genetics:

Answer 3

• Explain the genetic basis of continuous complex/multifactorial/quantitative traits
• Make no assumptions
• Focus on a populations
• Statistical and mathematical

Question 4

Genetic architechture:

Answer 4

• 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?

Question 5

How much variation is explained by genetic factors?

Answer 5

• Observe a phenotype to infer genetic causes (forward genetics)
• Focuses primarily on the genes inducing variation on those fundamental to a function

Question 6

Reverse genetics:

Answer 6

• Create genetic perturbation (mutations, insertions, transpositions) and observes the effects of these changes

Question 7

1. Decompose into linear effects

Answer 7

• Decomposing data into additive (alpha) and dominance (delta) effects
• The effects are linear and therefore independent from each other

Question 8

2. Variation calculation:

Answer 8

• • 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

Question 9

Heritability:

Answer 9

H squared = sigma squared to the base G/ sigma squared to the base P

Question 10

The fundamental components of measuring how much variation is explained genetically

Answer 10

• 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

Question 11

How many loci are involved?

Answer 11

• Observe the covariance between parents and offspring

- Interactive QTL mapping is a straightforward frame work

Question 12

1. Use the change of variance between parents and offspring

Answer 12

• 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)

Question 13

2. Using molecular markers, a step-wise inclusion of WTL to the model:

Answer 13

• Describes the iterative procedure of the WTL mapping strategy
• Find the first significant alpha and include the sum of G

Question 14

QTL are classified into major, minor QTL and infinitesimal/polygenic effects (infinite number of very small effects)

Answer 14

• We will never have the ability to measure these tiny tiny infinite effects

Question 15

The power to detect QTL depends on:

Answer 15

• sample size (to gain precise estimate of the variance components)
• the size of the effect/penetrance of the genetic effect

Question 16

Where are they located in the genome?

Answer 16

• Molecular marker evolution is so useful

Question 17

1. F2 derived from pure inbred lines:

Answer 17

• 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

Question 18

2. Advancing the resolution of QTL mapping near isogenic lines

Answer 18

• Testing a specific allele in a fixed and homogenous background
• One one allele combination is tested
• Development time is long

Question 19

2. Advancing the resolution of QTL mapping near recombinant inbred lines (RILs)

Answer 19

• More recombinations increase the resolution of the mapping

- All heterozygosity will be wiped out

Question 20

Advancing the resolution of WTL mapping with advanced intercross RILs (AI-RILs)

Answer 20

• Denser patterns

- Adding some generations to generate cross populations

Question 21

Advancing the resolution of QTL mapping with Heterozygous inbred families (HIFs)

Answer 21

• Use the residual heterozygosity to learn about the QTL effect (additive vs. dominance)

Question 22

Advancing the resolution of QTL mapping with multi-parent advanced intercross lines

Answer 22

• 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

Question 23

3. Association mapping:

Answer 23

• ## Trying to map genotype with gene sequence through phenotype measure, gene sequencing and genome-wide markers

Question 24

High resolution in QTL mapping is achieved by:

Answer 24

• Maximising the number of recombinations present in the populations
• Define small testable intervals
• Homogenise/reshuffle the genetic background to avoiding confounding

Question 25

Identifying the genes within the QTL:

Answer 25

- Positional cloning

Question 26

Positional cloning:

Answer 26

- 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

Question 27

Physical maps are used to:

Answer 27

Anchor genetic markers and increase fine-mapping resolution by deriving new markers within WTL interval of interest

Question 28

Positional cloning using microsynteny-based comparative mapping

Answer 28

- 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

Question 29

Synteny:

Answer 29

- 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