Lecture 19: Model Organisms For Analysis If Development And Disease

Question 1

What is traditional genetics and what is its pathway?

Answer 1

Forward gohenotype driven: random mutation > phenotype > gene identification > interpretation of gene function

Question 2

What is transgenesis and what is its pathway?

Answer 2

Reverse gene driven strategy that begins with clones gene of interest: gene identification > targeted mutation > phenotype > interpretation of gene function

Question 3

Why is random insertion so mutagenesis and what’s its pathway?

Answer 3

Gene trapping is an intermediate approach that introduces a tag so the mutated gene can be identified:
Random tag insertion > gene identification > phenotype > interpretation of gene function

Question 4

What is Pax6?

Answer 4

Transcription factor in eyes that has conserved amino acid sequences across different species

Question 5

What is forward genetics used for?

Answer 5

To uncover the genetic basis of a phenotype

Question 6

How is forward genetics carried out?

Answer 6

Mutagenesis by X-rays, chemicals, or transposons is used to generate mutant flies with aberrant phenotypes which are used as a starting point for gene discovery

Question 7

What is reverse genetics used for?

Answer 7

Discovery of gene function through targeted disruption/inhibition of genes and the analysis of resulting phenotypes

Question 8

What characteristics does a balancer chromosome have?

Answer 8

• engineered to contain nested chromosomes inversions
• cannot undergo crossing over
• contains markers
• contains lethal recessive allele

Question 9

What 3 mutations are found in zebra fish screens?

Answer 9

One eyes pinhead (oep): severe cyclopia
Weissherbst (weh): hyperchromic blood, decreasing blood cell counts
Hagoramo (hag): disrupted stripe pattern

Question 10

Synteny between humans and mice?

Answer 10

• limited to subchromosomal regions
• almost complete on the X chromosome

Question 11

How is patch mutation formed in mice?

Answer 11

Affects neural crest cells from which melanocytes derive, hence loss of pigmentation

Question 12

How does the node mutation affect mice?

Answer 12

No hair, no thymus, no mature T cells

Question 13

What is ENU?

Answer 13

N-ethyl N-nitrosourea is a supermutagen

Question 14

How does ENU work?

Answer 14

• transfers its ethyl group to oxygen and nitrogen radicals in DNA = mispairing
• indices single base pair substitutions in spermatogenial stem cells
• each F1 off spring from mutagenesis make carries up to 100 gene mutations

Question 15

What is missense mutation?

Answer 15

Amino acid substitution

Question 16

What is nonsense mutation?

Answer 16

Premature termination of the encoded protein

Question 17

What is hypomorph mutation?

Answer 17

A mutant allele that retains some of the gene function and is less severe than loss of function

Question 18

What is antimorph mutation?

Answer 18

A mutant allele that antagonises normal gene function

Question 19

What is neomorph mutation?

Answer 19

A mutant allele that acquires new function

Question 20

Why are outbred mouse strains useful?

Answer 20

• approximates human populations
• easy to maintain due to heterozygous vigour
• maintain mutants so don’t weaken and die

Question 21

Why are inbred mouse strains useful?

Answer 21

• each strain is unique
• made by brotherxsister matings for over 20 generations
• fixed genetic background, high probability of homozygosity
• limited genetic variation
• identify genes responsible for certain phenotype

Question 22

What is linkage?

Answer 22

When two different alleles are transmitted to offspring more frequently in parental combinations than in non-parental combinations

Question 23

How is recombination frequency determined and how does allele position effect it?

Answer 23

Number of recombinant progeny/total progeny
= increases with increasing distance between two different alleles on the same chromosome

Question 24

What does the term backcrossing mean?

Answer 24

Hybrid is crossed with one of its parents or an organism with the same genetic characteristics as one of the parents

Question 25

Why is backcrossing used?

Answer 25

To introduce trait locus into a defined genetic background to create a congenic strain

Question 26

How do 3 generation breeding schemes work for isolating recessive ENU mutation?

Answer 26

• G1 offspring represent gamete sample from mutated male
• pedigree is produced from G1malexWTfemale
• G2 females are mated back with G1 males to produce G3 offspring
• G3 offspring are screened for variation