Test2: Lect 12 Tamara Phillips

Question 1

Standard Inbred Strains: - Define: - Traits: - Jackson Laboratory tools:

Answer 1

• Define: made by generations of inbreeding, these are BALB/c or DBA or C57 - Traits: 1: Homozygous to others of their strain 2: Traits which are heritable stay stable over time (DBA from 30 years ago very similar genetically to a DBA now) 3: Sequenced on jackson laboratory, can see differences between strains 4: careful genetic records have been maintained - Jackson Laboratory tools: Have genomes Have chart identifying which strains are most different from each other.

Question 2

Checking if there is a genetic basis to a trait utilizing inbred strains:

Answer 2

1: Measure phenotypes of mice from different strains for 1 trait (say alcoholism) and another trait (say meth addiction). 2: Check to see if mice easily addicted to meth are easily addicted to alcohol 3: See if the means of the phenotypes correlate between the two strains.

Question 3

Describe Recombinant Mouse Generation

Answer 3

Mice crossed.

F1 inbred 20 generations.

Makes mixtures of the chromosomes, which can be labelled to see were the strains differ from each other.

Question 4

Quantitative Trait Locus (QTL) Mapping:

• What type of strains is it done with?
• What does it do for you?
• Explain how it is done:

Answer 4

• What type of strains is it done with?

Recombinant strains

• What does it do for you?

Allows you to look for where a specific gene may lie utilizing recombinant strains. Note there may be variation.

• Explain how it is done:

We are looking for a gene that affects alcohol consumption, low or high. The black sections correspond to mice where high is the base, white is normally low. A is a better match than B and C is the worst. THe C-56 black strain originally had this trait.

Question 5

If I run tests in my recombinant mouse lines and do QTL mapping, then have a program check for correlation with specific genes and there is a gene of interest, have I found the gene causing it?

Answer 5

Maybe, it might just be a linked gene to the gene of interest.

Question 6

Selected Lines:

• Define:
• Considerations:

Answer 6

• Define:

Select for high and low phenotype in newly recombinant mice

• Considerations:

How many mice strains should I mix?

Avoid inbreeding (selects for one background)

How many generations should I measure it out?

Replicate lines (see if they get the same result)

Control group (no selection should lead to a middle phenotype

Short term (less selection pressure) vs long term (more inbreeding, some artificial selection)

Question 7

Selected Lines:

• How do you avoid inbreeding while performing selection?
• Uses:

Answer 7

• How do you avoid inbreeding while performing selection?

Use large populations.

• Uses:
  1: Combine QTL mapping, see if you get a specific genotype for your trait
  2: Establish genetic influence (check to see if there is additive inheritence), measure realized heritability.
  3: establish heritavility of pleiotropic traits (genetic correlation)

Expression network analysis

Study a mechanism

Question 8

Selected Lines:

• Starting conditions:

Answer 8

• Starting conditions:
  1: Well defined phenotype (try to use one easy measure, rather than an index of several measures)
  2: Needs additive variance to work, won’t work on dominant variance (alleles not interactions are inherited)
  3: Should use genetically defined replicable starting population (like inbred mouse strain)

Question 9

What would the data look like for a genetic correlation study using selected strains of mice?

Answer 9

Question 10

Congenital strains:

• Purpose:
• Define/explain how to make one:

Answer 10

• Purpose:

Narrow down where the gene might be even more so than was possible with selected strains.

• Define:

Have a small area of chromosome from the other strain. You make it like this:

Question 11

How can you narrow down where the gene of interest may be after using a congenic strain?

Answer 11

Using multiple different congenic strains. Technique called: interval specific congenic strains

Question 12

Heterogenous stocks:
- Generated how?

Answer 12

• Generated how?

8 different strains interbred in all possible combinations into an F1. F1 interbred in all possible combinations, with recombination occuring to make F2. F2 is outbred and made into a very diverse stock.

Question 13

Heterogenous stocks:
- How can they be used?

Answer 13

• How can they be used?
  1: The F2 generation, and others can be used becuase the have an even finer difference in homology than the congenital strains have. Further narrows it down.
  2: Can correlate whether those in the “diversity outbred mouse” group have a correlation between your believed gene, and the trait the of interest.

2-1 Note: Avoid correlating only low and max phenotype groups. Use the whole population available.