L5 Developmental genetics

Question 1

How are genes named?

Answer 1

Genes are named after a protein product or the phenotype, whichever came first

Species names and gene names are italicised

Question 2

What are the main causes of random mutations?

Answer 2

Radiation (e.g. X-rays)
Chemical (e.g. base modifiers)

These changes can be point mutations (single base-pair), deletion, insertion, translocation

Question 3

Why are naturally occuring mutations important?

Answer 3

Naturally occurring mutations are important for evolution, but also are a major cause of disease.

Question 4

What are inherited mutations called?

Answer 4

Germline mutations

Inherited so from sperm or oocyte

Question 5

What is somatic mutation?

Answer 5

Somatic mutations are just in our body.

Question 6

How are mutation changed caused?

Answer 6

They are caused by radiation or chemicals.

Question 7

What are the two types of developmental genetics?

Answer 7

1. Forward Genetics (Mutagenesis).
2. Reverse Genetics

Question 8

What is forward genetics?

Answer 8

• Approach begins with observing a mutant phenotype
• Researchers then work to identify the gene or genes responsible for that phenotype
• Essentially, it moves from “phenotype to genotype”

Question 9

What is reverse genetics?

Answer 9

• Approach starts with a known gene or DNA sequence.
• Researchers then manipulate that gene (e.g., by mutating it) and observe the resulting phenotype.
• Therefore, it moves from “genotype to phenotype”

Question 10

What does mutagenesis mean?

Answer 10

This is the process of causing mutations

It can involve exposing organisms to mutagens, which are agents that cause mutations

Question 11

What are the major ways of targeting specific genes in reverse genetics?

Answer 11

1. CRISPR
2. Gene Knock-out

Question 12

What is gene knock-out?

Answer 12

Complete removal of gene to determine its function.

Question 13

What is the major adavantage of CRISPR?

Answer 13

It works in any organisms

Question 14

How does gene replacement work?

Answer 14

Gene replacement (knock-in) usually makes a small changes to the endogenous gene.

Question 15

What is the difference between forward and reverse genetics?

Answer 15

Forward - Phenotype to gene
Reverse - Gene - Phenotype

Question 16

What three ways of mutation that affects genes?

Answer 16

1. Changes in regulatory sequences (in the DNA that affects transcription)
2. Changes in non-coding sequences (of the transcript that may affect RNA splicing, stability or translation)
3. Changes in the coding sequence (may alter an important amino acid affecting folding of the protein or may create a premature stop codon)

Question 17

What do changes in regulatory sequences in DNA affects?

Answer 17

Transcription

Question 18

What do changes in non - coding sequences of the transcript affect?

Answer 18

They may affect RNA splicing, stability or translation.

Question 19

What do changes in coding sequence alter?

Answer 19

May alter an important amino acid affecting folding of the protein or may create a premature stop codon - truncated protein.

Missense = single amino acid substituted. Nonsense = stop codon

Question 20

What is a domain?

Answer 20

A domain is a functional unit in a protein.

Question 21

What is a dimer?

Answer 21

A dimer is when two of the same protein bind together.

Question 22

What do you mean by conformational change?

Answer 22

A conformational change is a change in protein structure

Question 23

List the processes of mutations affecting protein function.

Answer 23

1. DNA binding
2. dimerization
3. conformational change
4. Transcriptional activation

Question 24

Give an example of amorphic/non-functioning mutation.

Answer 24

An example is a missense mutation that completely inactivates the DNA binding domain.

Question 25

Give an example of hypomorphic/weakened mutation.

Answer 25

for example a missense mutation that weakens the DNA binding domain.

Question 26

Give an example of antimorphic/dominant negative mutation.

Answer 26

for example a missense mutation that destroys the dimerisation domain.

Question 27

Give an example of hypermorphic/overactive mutation.

Answer 27

for example a missense mutation that results in activation that is independent of dimerization.

Question 28

What are the 4 types of mutations? (Muller's Morphs)

Answer 28

Loss of function mutations: 1. Amorphic 2. Hypomorphic 3. Antimorphic Gain of function mutation: 4. hypermorphic

Question 29

What is Muller's morphs?

Answer 29

Types of phenotypes produced by mutations

Question 30

What is amorphic?

Answer 30

Complete loss of gene function: typically early nonsense mutations or a deletion of the entire gene

Question 31

What is hypomorphic?

Answer 31

Partial loss of gene function/ reduction of wild type function: typically missense mutations. Usually recessive

Question 32

What are missense mutations?

Answer 32

A "missense mutation" is a specific type of point mutation within DNA

Question 33

What is antimorphic?

Answer 33

Acts as competitive inhibitors, typically mutations that affect one domain of a protein. Also called dominant negative

Question 34

What is hypermorphic?

Answer 34

Over expression of the transcription unit or over activity of the gene product: for example mutation in a binding site for a repressor. Dominant

Question 35

Which type of Muller's Morphs mutations are recessive or dominant?

Answer 35

Amorphic - Recessive Hypomorphic - Recessive Antimorphic - Dominant negative Hypermorphic - Dominant

Question 36

What does mutations that result in the same phenotype despite being in different genes suggest?

Answer 36

Mutations that result is the same phenotype that are not in the same gene suggest that the genes function in the same pathway

Question 37

What are alleles?

Answer 37

Mutations that result is the same phenotype may be different mutations in the same gene. Mutations in the same gene are called alleles.

Question 38

What do reprter constructs help us to study?

Answer 38

Reporter constructs helps us to study gene and mutations in vivo.

Question 39

What is GFP?

Answer 39

Green Fluorescent Protein

Question 40

What is transfection?

Answer 40

The process of introducing foreign genetic material (like DNA) into cells

Question 41

How do you generate a GFP transgenic line?

Answer 41

1) Genomic DNA with all of the regulatory elements 2) Genitcally engineer GFP onto the end of the last exon (gene fusion) or replace the gene (reporter construct) 3) Re-introduce this into the animal

Question 42

What is a transgenic line?

Answer 42

A cell line or organism whose genome has been altered by the insertion of foreign DNA.

Question 43

What are the uses for GFP transgenic lines?

Answer 43

To follow expression of a gene or to follow the behavior of cells in vivo. To follow subcellular localisation of a protein.