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Model organisms in genomic research

30 important questions on Model organisms in genomic research

Why are humans not suitable as model organisms?

It is unethical to use them as model organism
They have a long generation time
They are difficult to genetically manipulate
It would be expensive

How can you use model organisms to investigate whether a phenotypical difference (for example, body weight) between siblings is causal or a coincedence?

- You can look for a mutation that the one has and the other does not have,
- and then you can recreate it in a model organism.

What is the difference between forward and reverse genetics?

- Forward: you create random mutations and go from phenotype to genotype
- Reverse: you create a specific mutation and go from genotype to phenotype

What is a requirement for forward genetics?

You need to be able to breed in high numbers

What is the number of protein-coding genes and the number of chromosomes of yeast?

- Protein-coding genes: around 6,000
- Number of chromosomes: 16

What is the number of protein-coding genes and the number of chromosomes of fruit flies?

- Protein-coding genes: around 14,000
- Number of chromosomes: 4

What is the number of protein-coding genes and the number of chromosomes of mice?

- Protein-coding genes: around 22,000
- Number of chromosomes: 20

What is the number of protein-coding genes and the number of chromosomes of humans?

- Protein-coding genes: around 19,000
- Number of chromosomes: 23

How is the sex of haploid yeast determined, and what are the two options?

- It depends on which MAT allele is expressed,
- and it can be either a or α

What happens with the diploid a/α yeast upon starvation?

Meiosis sporulation takes place, tetrads are formed and from those haploid a or α yeast cells are formed.

What is a gene knockout strategy in yeast (reverse genetics)?

- You use a selection marker (for example URA3),
- homologous recombination takes place at the position of your favorite gene,
- the selection marker comes in the place of your favorite gene

How can forward genetics be done in yeast?

- You let yeast grow,
- add a mutagen,
- plate them out (and you can look at differences)

What is the problem with the forward genetics method in yeast?

For a lot of genes, disabling them will affect the viability (so only certain yeast cells with less severe mutations will appear)

What is a solution for the problem with forward genetics in yeast?

- When temparature-sensitive mutations occur, they will often only give a problem at a higher temparature,
- so you let them first grow at a lower temparature,
- and then make the temparature higher,
- and see which cells have disappeared

What is an example of temparature-sensitive mutants?

Cell Division Cycle mutants (CDC mutants) (the temparature-change method is needed, because yeast cells do not survive with the CDC mutant as the cell cycle is very important)

What are important characteristics of C.elegans?

- It is a nematode
- Lives in soil, growing on microbes
- 959 cells, of which 302 neurons (which are not necessary for survival)

Why can C.elegans be very useful as a model organism?

- Small, easy, can be frozen
- Gene manipulation by feeding E.coli with DNA
- Short generation time, self-fertilizing
- Transparent body
- Easy RNAi manipulation

What happens to C.elegans when conditions are less optimal (for example starvation or draught)?

They turn into Dauer larva, which are inactive. When conditions are normal again, they can turn into active larva very fast.

When you induce mutations in C.elegans, how many generations does it take to get 100% homozygous recessive for the mutation (when you take the homozygous recessive animals for the last generation)?

3 (F1, F2, F3), F1 = heterozygous for the mutation, F2 = 25% homozygous for mutation, F3 = 100% homozygous

How many C.elegans genes have human equivalents?

Around 35%

Which well-known process is discovered in C.elegans?

Programmed cell death (C.elegans develops into more than 1,000 cells, and a few die so that it ends up with 959 cells)

How is genetic manipulation in C.elegans often done?

By an injection in syncytium, shared cytoplasm of the gonads

What is the generation time of Drosophila?

10 days

Besides the short generation time, what are advantages of the use of Drosophila as a model organism?

Easy, cheap, interesting behaviours and phenotypes, genetic approaches very well developed

Which 2 things are discovered by Thomas Hunt Morgan, using Drosophila?

1. The (recessive) white-eyed trait only occured in males -- the eye colour is linked to the sex chromosome -- genes have certain positions on chromosomes
2. Genetic linkage (in centimorgans)

Why are balancer chromosomes needed when studying recessive lethal mutations?

Because the homozygous recessive fruit flies for this trait will die, the mutation will disappear from the population.

What is a balancer chromosome?

An artificial lethal recessive chromosome, which keeps the population stable

What do balancer chromosomes contain?

- A recessive lethal marker
- A dominant selectable marker
- Inversion decrease recombination frequency between chromosomes during meiosis -- all genes are intact

Why are mice used a lot in genomic research?

- Evolutionary close to humans
- Relatively short generation time
- Genetic engineering: embryonic stem cells can be injected into the blastocyst (you need multiple generations to establish a mouse line with the mutation)
- Fertilized oocytes can be stored and frozen

What kind of genomic research are mice used for the most?

Reverse genetics (understanding a disease, medication), as forward genetics is not considered very ethical, desirable and feasible

The question on the page originate from the summary of the following study material:

Medical Genomics

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