Lecture 19: Model Organisms For Analysis If Development And Disease Flashcards
What is traditional genetics and what is its pathway?
Forward gohenotype driven: random mutation > phenotype > gene identification > interpretation of gene function
What is transgenesis and what is its pathway?
Reverse gene driven strategy that begins with clones gene of interest: gene identification > targeted mutation > phenotype > interpretation of gene function
Why is random insertion so mutagenesis and what’s its pathway?
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
What is Pax6?
Transcription factor in eyes that has conserved amino acid sequences across different species
What is forward genetics used for?
To uncover the genetic basis of a phenotype
How is forward genetics carried out?
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
What is reverse genetics used for?
Discovery of gene function through targeted disruption/inhibition of genes and the analysis of resulting phenotypes
What characteristics does a balancer chromosome have?
- engineered to contain nested chromosomes inversions
- cannot undergo crossing over
- contains markers
- contains lethal recessive allele
What 3 mutations are found in zebra fish screens?
One eyes pinhead (oep): severe cyclopia
Weissherbst (weh): hyperchromic blood, decreasing blood cell counts
Hagoramo (hag): disrupted stripe pattern
Synteny between humans and mice?
- limited to subchromosomal regions
- almost complete on the X chromosome
How is patch mutation formed in mice?
Affects neural crest cells from which melanocytes derive, hence loss of pigmentation
How does the node mutation affect mice?
No hair, no thymus, no mature T cells
What is ENU?
N-ethyl N-nitrosourea is a supermutagen
How does ENU work?
- 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
What is missense mutation?
Amino acid substitution
What is nonsense mutation?
Premature termination of the encoded protein
What is hypomorph mutation?
A mutant allele that retains some of the gene function and is less severe than loss of function
What is antimorph mutation?
A mutant allele that antagonises normal gene function
What is neomorph mutation?
A mutant allele that acquires new function
Why are outbred mouse strains useful?
- approximates human populations
- easy to maintain due to heterozygous vigour
- maintain mutants so don’t weaken and die
Why are inbred mouse strains useful?
- 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
What is linkage?
When two different alleles are transmitted to offspring more frequently in parental combinations than in non-parental combinations
How is recombination frequency determined and how does allele position effect it?
Number of recombinant progeny/total progeny
= increases with increasing distance between two different alleles on the same chromosome
What does the term backcrossing mean?
Hybrid is crossed with one of its parents or an organism with the same genetic characteristics as one of the parents
Why is backcrossing used?
To introduce trait locus into a defined genetic background to create a congenic strain
How do 3 generation breeding schemes work for isolating recessive ENU mutation?
- 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
