BCA lecture 3

Question 1

Important characteristics of genetic model organisms?

Answer 1

simplicity
genetic toolbox available
genetic conservation
versatile

Question 2

type of Mutation based on their impact in gene’s function

Answer 2

loss of function: inactivating the function/expression of a protein
gain of function: activating more than normal function/expresssion

Question 3

explain 3 ways to disturb a gene expression

Answer 3

DNA level: gene knockout (mutating the DNA so the gene cannot be expressed)
RNA level: gene knockdown (interfering with RNA to reduce the level of gene expression)
Protein level: protein degradation (degrade the protein that are expressed by the genes, for example auxin-inducible degron)

Question 3

explain reverse and forward genetics

Answer 3

Reverse genetics refers to the process of identifying the gene responsible for a particular phenotype (observable characteristic or trait) by manipulating the expression of gene(s) and observing the effect on the phenotype

forward genetics refers to the approach od random mutagenesis and then screen for phenotype of interest and look for the genes responsible

Question 4

explain Wnt signalling

Answer 4

in the absence of Wnt signalling, B-catenin is targeted for degradation by protein complex that consists of axin, APC, and kinases which phosphorylate B-catenins and degrade them

when Wnt signalling is received by frizzled receptor and LRP6, the protein complex releases APC and binds towards the receptor complex resulting in the inhibition of B-catenin degradation. afterwards, B-catenin translocate into nucleus and interacts with TCF/Lef1 to co activate target gene

Question 5

how to create transgenic worms

Answer 5

1. prepare plasmid with genes that want to be inserted
2. microinjection into the gonad of the worms, causing the worms to have the phenotype from the gene but still not integrated (exogenous chromosome)
3. in order to fully integrate the gene, the worms needed to be irradiated with UV or gamma radiation and let to be reproduce for several generations until stable

Question 6

give 4 examples of commonly used animal models other than C. elegans and explain why they are beneficial

Answer 6

fission yeast (Saccharomyces pombe)
fast growth rate, easy to manipulate genetically, similarity to higher eukaryotes, transparent/easy to observe

fruit fly (Drosophila sp.)
short generation time, large number of offspring, easy too culture, well-studied genome, simple but complex (neuron system is complex enough)

zebrafish (Danio rerio)
vertebrae, cardiocirculatory system, able to regenerate, possible for both rv and fw genetics

mouse (Mus musculus)
strong homology with human genome, short life span, possible to manipulate the genome

Question 7

how to knock out a gene in mice

Answer 7

blastocyst injection
a mouse embryonic stem cell with KO gene is inserted into the blastocyst of a donor mouse and the offspring will contain the KO gene

Question 8

homolog and ortholog

Answer 8

Homologs are genes related by descent from a common ancestral gene.

ortholog are genes in different species that evolved from a common ancestral gene by speciation. They usually retain the same function across species.

all orthologs are homologs, but not all homologs are orthologs.