Lecture 30 Flashcards
What is a genetic screen? How do we do and use this? Why is this necessary?
A genetic screen is making and analysing lots of mutants. By studying organisms which are mutant for a particular gene we can work out what the gene might do, we produce these mutants by treating organisms with radiation and chemicals and the genetic screens are designed to find mutations that affect a process or structure we are interested in.
Genetic screens are necessary because naturally occuring mutants are rare. The use of the genetic screen accelerates this mutation rate.
What are some model organisms for genetic screens?
Drosophila melanogater (fruit fly), mus musculus (mouse), caebirhabditis elegans (an eel), Danio rerio (a fish) and arabidopsis thaliana (a plant). These are all ideal due to their rapid life cycles and small size(makes them cheap and easy to store).
Why are mutations useful for understanding development?
Development of the embryo directs cells to become different types, sizes and shapes to form structures in the body. Because this is a genetically controlled process mutated genes can affect it.
What was the heidelberg screen? What process was used to create mutants? What was it primarily looking for?
The heidelberg screen aimed to determine genes which affected embryonic development of the fruit fly. It worked on the principle that essentially any mutation which led to the offspring not surviving (particularly homozygous) must code for traits necessary for development.
The embryos were produced by feeding male flies chemical mutagens, these flies now with mutated gametes were then imbred with their mother and then the siblings were bred to ensure homozygous traits and then tested to see if the homozygous enbryos die.
Primarily the Heidelberg screen was looking for changes in the embryonic pattern of the fruit fly development, the dead embryos had their cuticle patterns checked. Ones with defective cuticles had a mutation which affects segmentation. As such every mutant represents a single gene involved in segmentation. This was repeated until all genes involved in segmentation were found.
What is positional cloning?
Positional cloning is a process which is used to clone the mutant gene of an affected phenotype, this can then be used to identify similar genes in other species (e.g us).
Summarise genetic screening.
Decide what process or structure you are interested in, perform a genetic screen, pick mutants with defects in the thing you want to study, use these mutants to discover what the mutant genes would do normally.
Using this technique the function of the gene is known before the sequence.
What are the advantages and disadvantages of using mice as a model organism?
Advantages: mammalian (share many biological functions with humans), human and mouse genoms are the same size and many genes are in synteny, 9% of mouse genes have human homologues, a similar immune system, small and easy to maintain with fast breeding, inbred lab strains which reduce variation and good infrastructure and resources due to the large amount of labs using mice.
Disadvantages: mouse physiology can differ from humans, more expensive than other models and ethics concerns.
What is trangenesis? How is it typically done in mice?
Trangenesis is the putting of a foreign gene in an animal.
In mice: take fertilised egg and insert DNA into the male pronucleus using a very small needle, place this egg into a foster mother.
What is knockout mice and what is it used for?
This refers to removing or replacing the gene (‘knocking out’ a gene) we are interested in by genetically modifying the mice, through examining this GMO we can work out what the gene normally does. This can be done for any gene as long as you know the sequence first and is as such used to work out the function when you only know the sequence.
Why are animal models not always perfect for humans? What can still be tested for on these animals?
Many reasons, the disease may not act in the same way on the model animal. Gene therapy (repair or replacement of the damaged protein/gene) or drug therapy (treating the chronic symptoms) can still be tested on these.
