1: Mapping genes affecting phenotypes

Question 1

Describe how to do a genotype a mapping cross

Answer 1

• Molecular markers, spaced through genome → distinguish 2 parental types
• Diagnostic: Perform stat test at each marker to work out whether any marker is associated with the phenotype of interest

Question 1

Describe how to make a mapping cross

4 steps

Answer 1

1. Cross 2 parental types (Closely related species OR Inbred lines of same species
2. Cross hybrid offspring (F1 gen) with each other
3. Recombination takes place during meiosis, shuffling the parental genomes around
4. The progeny of the F1 cross (F2 gen), inherit recombined parental genomes
   - The F2 are different from each other.
   - Several hundred F2 individuals required for mapping

Question 2

What is a QTL?

Answer 2

Quantitative trait locus
- a specific genomic region associated with the inheritance of quantitative traits (e.g height, weight)

Question 3

What is an Extended phenotype?

Answer 3

How an organism interacts with its environment e.g spidersweb, birds nest, termites mound
→ genetically innate to organism but not physically attached to them

Question 4

Describe Manhattan plots

Answer 4

Each dot represents a SNP marker
Y axis - p value, converted to a -log10 scale
‘Skyscrapers’ regions with genes that explain variation
Horizontal line is the genome wide significance threshold → generally 10-log10

Question 5

Describe the study into the genetics of burrowing in Mice

Answer 5

• Oldfield mice build long tunnels with an escape tunnel (adaption to avoid predators).
• Crossed with Deer mice (short tunnel and no escape tunnels) = intermediate
• Backcross between F1 and hybrid
  = Linkage mapping found evidence for QTL

Question 6

What does study into the genetics of human height suggest?

Answer 6

• Human height heritable but even the biggest studies cannot find most of the genes - the missing heritability problem
• Wood et al. (2022) conducted probably the biggest GWAS ever
  = Suggests that the classical view of quantitative traits - determined by many genes of tiny effect is correct

Question 7

Compare the mapping population in linkage mapping vs GWAS

Answer 7

Linkage:
cross between divergent lines/ species
OR
a family/pedigree of a few gens

GWAS:
- Random sample from a population
- No cross/pedigree required

Question 8

What does GWAS stand for?

Answer 8

Genome wide association study

Question 9

Compare the role of recombination in Linkage mapping vs GWAS

Answer 9

Linkage:
- test relies on recombination that occurs between markers and QTL within the generations under study

GWAS:
- test relies on ancestral recombination between markers and QTL

Question 10

Compare the number of markers in linkage mapping vs GWAS

Answer 10

linkage:
- 100s - a few thousand

GWAS:
- 5,000 - 1.5 million or more

Question 11

Comapre the resolution of linkage mapping vs GWAS

Answer 11

Linkage:
- rough
- QTL can only be mapped to an approximate part of the chromosome

GWAS:
- Much finer
- QTL can be mapped to within individual genes

Question 12

Compare the risks of Linkage mapping vs GWAS

Answer 12

Both:
- Many tests performed
- Need to control for false positives