Lecture 16 - Genetic changes and protein function Flashcards
What carries out translation?
RIbosomes
Where does translation occur?
the cytoplasm
What is the purpose of translation?
Making a polypeptide chain using the message encoded by mRNA
What does mRNA do?
Tells amino acids the correct order to join together in
What are ribosomes?
complex structures made of protein and rRNA
How do ribosomes work?
They work like enzymes to catalyse protein synthesis (peptide bond reaction)
What are the four unique bases in DNA?
Adenine, Cytosine, Guanine, Thymine
What are the four unique bases in RNA?
Adenine, Cytosine, Guanine, Uracil
How is the four-base code of DNA translated to the 20 different amino acids?
The DNA/RNA is read in sets of three called codons
What is the codon system known as?
Since it is common across all life it is known as the universal genetic code
What reads the codons in mRNA?
tRNA
What is the complementary sequence to the mRNA codon called in tRNA?
anti-codon
What does cytosine pair with?
Guanine
What does adenine pair with?
Thymine (in DNA) or Uracil (in RNA)
What are the key features of tRNA?
- Anticodon
- Amino acid attached
How does tRNA create a peptide chain in the correct order?
Every codon/anti-codon sequence has a particular amino acid that it pairs with. The tRNA attaches to the amino acid and only the amino acid that matches that tRNA molecules anti-codon will be able to attach
What happens during translational initiation?
The ribosome, mRNA, and first tRNA come together to form the translational initiation complex. The first tRNA always codes for Methionine
What happens during translational elongation?
The ribosome moves along the mRNA, adding amino acids to the growing peptide chain
What happens during translational termination?
A stop codon indicates the peptide chain has all the necessary amino acids and causes the translational complex to break apart. The newly formed peptide chain releases
How many possible codons are there?
64
How many amino acids are there?
20
How many codons code for ‘stop’?
3
Which amino acids have only one codon that codes for them?
Methionine, Tryptophan
What does codon redundancy do?
As most amino acids have multiple codons that code for them, this allows for some flexibility in gene sequence without changing the protein
What does genetic variation mean?
differences between the DNA sequences of members of the same species
How much does the genome vary between humans?
0.1%
What does genetic variation help with?
- determine who is who
- helps species survive
- helps organisms adapt to their environment and any changes that occur
What are different forms of a variant called?
alleles
What are genetic variants classified by?
- Number of DNA bases involved
- Style of DNA sequence involved
- Location of the change
What is a SNP?
single nucleotide polymorphism, a single base change in the DNA sequence
What is an INDEL?
insertion-deletion, the addition or removal of one or more bases
Where do regulatory variants occur?
In transcription factor binding sites in the promoter
Do genetic variants always have effects?
No depends on where it is in the genome and the type of variant
Do variants in the regulatory region change expression of a gene?
Sometimes as they may change the amount of protein that is produced
What type of variation may change the amino acid sequence?
Variants within the exon of a gene
What do the majority of gene variants do?
Neutral - no effect
What different things can SNPs that change a codon do?
- Code for the same amino acid
- Code for a different amino acid
- Code for a stop, causing a truncated protein
What may InDels that are not a multiple of 3 base pairs cause?
A frame shift, usually resulting in serious consequences for the protein
What do the consequences of a missense genetic variant depend on?
- Where in the protein the amino acid change occurs
- how chemically similar/different the two amino acids are
- Whether the amino acid breaks an essential structure
- The original function of the protein
Can every type of protein be affected by a genetic variant?
Yes
When will a variant be lethal?
When a variant causes complete loss of function to a protein essential for life
What contributes to the wide variety of differences between organisms?
The fact that every type of protein can have any type of genetic variant
What is the gene name for the two alpha-haemoglobin chains?
HBA1
How many coding variants are there for the HBA1 gene?
> 500
What is the gene name for the two beta-haemoglobin chains?
HBB
How many coding variants are there for the HBB gene?
> 1400
What is a coding variant?
Any variant found in the exons of a gene
What causes sickle cell anaemia?
Mutation in HBB E6V gene - 6th amino acid in beta-haemoglobin changed from glutamic acid to valine. Causing Hb protein to clog blood vessels
What causes Methaemoglobinaemia?
Mutation in HBB H64Y - 64th amino acid in beta-haemoglobin changed from histidine to tyrosine. Fe3+ haem unable to bind oxygen
What are the majority of recorded variants in Haemoglobin?
synonymous or benign missense changes
What examples of pathogenic missense variants of haemoglobin?
Sickle cell anaemia, Methaemoglobinaemia
What do consequences of missense genetic variants to an organism depend on?
- How important the proteins job is
- Whether another protein can compensate for the changed proteins function
- The inheritance pattern of the protein
How do tabby and solid cats vary?
- ASIP in cats creates tabby stripes
- Due to genetic variant : 2-bp deletion in exon 2 of ASIP (c.123delCA), known as the “non-agouti allele” solid cats have a non functioning ASIP
- Causes a frameshift which disrupts the proteins function
