D1.3 Mutation & Gene Editing

Question 1

Why are knockout organisms useful to scientists studying the function of specific genes?

Answer 1

To study how a specific gene may cause/contribute to human disease

Question 2

causes of mutation within a species

Answer 2

Meiosis, mutation and random fertilisation

Question 3

What happens during huntingtons disease

Answer 3

• trinucleotide repeat expansion
• many copies of CAG are added to HTT gene
• in chormosome 4

Question 4

Sickle Cell Anemia

Answer 4

*due to single base substitution of A to T
* 6th triplet changes from GAG (GLU) to GTG (VAL)
* mRNA codon CUG to CAG
* alters AA sequence in haemoglobin
* blood cells are in sickle shape instead of biconcave disk
* takes up less O2

FYI: causes heart stroke/attack, bone malformation, pneumonia
1. long fibres poke into cell membrane = distorts shape
2. ability to carry oxygen decreases
3. block blood vessels
4. puts strain on liver as it removes cells
5. bone marrow has to continuously produce more

• prim & second structure of Beta subunit is altered
• quaternary structure of haemoglobin changes
• fibres are deformed

Question 5

mutation

Answer 5

change in the genetic composition of a cell

Question 6

single nucleotide polymorphism

Answer 6

Replacement of a single nucleotide with another, producing variation within a species.
* synonymous
* non synonymous

Question 6

Synonymous mutation

Answer 6

change in the DNA sequence resulting in the production of the same amino acid

silent mutation

Question 6

non synonymous

Answer 6

change in the DNA sequence resulting in the production of a different amino acid

Question 7

Frameshift mutation

Answer 7

Mutations altering the reading frame of a DNA sequeneces triplets

• insertion
• deletion

Question 8

Types of base substituation methods

Answer 8

• nonsense= stop codon
• missense= wrong AA
• same sense= same AA

Question 9

Causes of mutations

Answer 9

• errors in DNA replication
• mutagens

Question 9

Mutagen

Answer 9

Chemical/physical agents which have the ability to alter genetic sequences

Question 10

Mutagen examples

Answer 10

chemical
* mustard gas
* nitrous acid
* ethyl urethane
* formaldehyde

physical
* UV
* X Ray

Question 11

Randomness of Mutation

Answer 11

• cytosine is most likely= spontaneous: deamination
  => loses amine group = turns to uracil

Question 12

Somatic cells

Answer 12

all body cells except germ cells

Question 13

Effects of mutations to proteins

Answer 13

• same P produced
• different but functioning P produced
• non functioning P produced
• no protein produced
• improvement

=> genetic variation

Question 14

Pros & Cons of gene mutation

Answer 14

Pros
* better survival rate
* better adaption
ex: sickle cell = malaria resistance

Cons
* out of control cell multiplication
* mutation opf gamete = death of foetus
ex: Cystic Fibrosis, Haemophilia, Red-green color blindness, huntingtons disease

Question 14

Effects of mutations to cells

Answer 14

Somatic = disease (not passed to offspring)

germ= inhertited mutations

Question 15

Gene Mutation Diseases

Answer 15

Cystic Fibrosis, Haemophilia, Red green color blindness, Huntingtons disease

Question 16

gene knockout

Answer 16

technique in which a specific gene is intentionally removed or changed so that the expression of it is permanently prevented

Question 17

Knockout orgnaism example

Answer 17

Obese knockout mice
* leptin= hormone involved in regulating energy intake vs expernditure
* removed coding segment for leptin
=> Mice rapidly gained weight

Question 18

P53 - Knockout gene

Answer 18

• when P53 is inactive = higher prevelance of cancerous growth
• inhibts tumor development

Question 19

CRISPR- Cas9

Answer 19

Clustered Regularly Interspaced Palindromic Repeats
Cas9= endonuclease enzyme which cuts specific target sites

Question 20

CRISPR Mechanism

Answer 20

1. foreign DNA that matched CRISPR spacer = corresponding crRNA molecule identifies & binds to iral sequence
2. guides Cas9 to target DNA
3. Cas9 makes precise cuts
4. double strand break = can be repaired by cells DNA machienery

Question 21

Use of CRISPR in gene editing

Answer 21

* RNA targets & binds to particular DNA sequnece * adapted in genetic engeneering * scientists can add, delete or modify DNA at that point

Question 21

Ethical Implication of CRISPR

Answer 21

* gene therapy = treating by correction * agriculture= enhance traits * disease modelling= insight & forecast * genetic engeneering= pharma & enhance production

Question 22

conserved dna

Answer 22

sequneces that remian indentical accross a species or group of species => very little genetic mutation

Question 23

conservation hypothesis

Answer 23

1. Functional constraints; selective pressures that prevent the accumulation of mutations that disrupt the function of a gene or its products => unhelpful mutations wont persist 2. Slower rates of mutation ; natural selection pushes mutation rates down to a lower limit set by the power of random genetic drift rather than by intrinsic physiological limitations. => reduced levels of replication, transcription, translation.