D1.3 Mutation & Gene Editing Flashcards
Why are knockout organisms useful to scientists studying the function of specific genes?
To study how a specific gene may cuase/contribute to human disease
causes of mutation within a species
Meiosis, mutation and random fertilisation
What happens during huntingtons disease
- trinucleotide repeat expansion
- many copies of CAG are added to HTT gene
- in chormosome 4
Sickle Cell Anemia
- blood cells are in sickle shape instead of biconcave disk
- causes heart stroke/attack, bone malformation, pneumonia
- due to single base substitution of A to T
- 6th triplet changes from GAG (GLU) to GTG (VAL)
- prim & second structure of Beta subunit is altered
- quaternary structure of haemoglobin changes
- fibres are deformed
- long fibres poke into cell membrane = distorts shape
- ability to carry oxygen decreases
- block blood vessels
- puts strain on liver as it removes cells
- bone marrow has to continuously produce more
mutation
change in the genetic composition of a cell
single nucleotide polymorphism
Replacement of a single nucleotide with another, producing variation within a species.
* synonymous
* non synonymous
Synonymous mutation
change in the DNA sequence resulting in the production of the same amino acid
silent mutation
non synonymous
change in the DNA sequence resulting in the production of a different amino acid
Frameshift mutation
Mutations altering the reading frame of a DNA sequeneces triplets
- insertion
- deletion
Types of base substituation methods
- nonsense= stop codon
- missense= wrong AA
- same sense= same AA
Causes of mutations
- errors in DNA replication
- mutagens
Mutagen
Chemical/physical agents which have the ability to alter genetic sequences
Mutagen examples
chemical
* mustard gas
* nitrous acid
* ethyl urethane
* formaldehyde
physical
* UV
* X Ray
Randomness of Mutation
- cytosine is most likely= spontaneous: deamination)
0> loses amine group = turns to uracil
Somatic cells
all body cells except germ cells
Effects of mutations to proteins
- same P produced
- different but functioning P produced
- non functioning P produced
- no protein produced
- improvement
=> genetic variation
Pros & Cons of gene mutation
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
Effects of mutations to cells
Somatic = disease (not passed to offspring)
germ= inhertited mutations
Gene Mutation Diseases
Cystic Fibrosis, Haemophilia, Red green color blindness, Huntingtons disease
gene knockout
technique in which a specific gene is intentionally removed or changed so that the expression of it is permanently prevented
Knockout orgnaism example
Obese knockout mice
* leptin= hormone involved in regulating energy intake vs expernditure
* removed coding segment for leptin
=> Mice rapidly gained weight
P53 - Knockout gene
- when P53 is inactive = higher prevelance of cancerous growth
- inhibts tumor development
CRISPR- Cas9
Clustered Regularly Interspaced Palindromic Repeats
Cas9= endonuclease enzyme which cuts specific target sites
CRISPR Mechanism
- foreign DNA that matched CRISPR spacer = corresponding crRNA molecule identifies & binds to iral sequence
- guides Cas9 to target DNA
- Cas9 makes precise cuts
- double strand break = can be repaired by cells DNA machienery
Use of CRISPR in gene editing
- RNA targets & binds to particular DNA sequnece
- adapted in genetic engeneering
- scientists can add, delete or modify DNA at that point
Ethical Implication of CRISPR
- gene therapy = treating by correction
- agriculture= enhance traits
- disease modelling= insight & forecast
- genetic engeneering= pharma & enhance production
conserved dna
sequneces that remian indentical accross a species or group of species
=> very little genetic mutation
conservation hypothesis
- Functional constraints; selective pressures that prevent the accumulation of mutations that disrupt the function of a gene or its products
=> unhelpful mutations wont persist - 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.
