Exam 1 - Lecture 3 Flashcards
Mutations
What is a mutation?
a structural change in genomic DNA which can be transmitted from a parental cell to its daughter cells
What is the difference between germline and somatic mutation?
Germline mutation: present in the gamete
Somatic mutation: present in the somatic cell
What are the types of mutations?
1a. Point mutations (coding)
1b. Regulatory point mutations
1c. Alternative splicing
2a. Deletions/insertions
3. Retrotransposition-related problems
4. Unstable repeat expansion
Substitution mutation
Substitutions will only affect a single codon
Their effects may not be serious unless they affect an amino acid that is essential for the structure and function of the finished protein molecule (e.g. sickle cell anaemia)
silent mutation
A silent mutation has no effect on the phenotype (many exclusions present)
What codons resist mutations more than others?
VAL (valine): GUU, GUA, GUC, GUG
What is an example of missense mutation?
Sickle cell anemia
What is an example of a nonsense mutation?
Familial Hypercholsterolemia (LDLR)
Why does LDLR not make it into the membrane?
when a Protein is too short, It can not fold properly, and Because of that, LDLRs never make it into the membrane and got degraded in ER
How is sickle cell causes?
The change in amino acid sequence causes hemoglobin molecules to crystallize when oxygen levels in the blood are low. As a result, red blood cells sickle and get stuck
in small blood vessels
What is an example of a frame shift mutation?
cystic fibrosis
How is cystic fibrosis caused?
Protein amino acid sequence is shifted, Plus it is too short due to unexpected stop-codon.
It can not fold properly. Because of that, CFTR channel never make it into the membrane and got degraded in ER
What is the function of CFTR protien?
a Cl- channel
What is nonsense medicate mRNA Decay?
Detection of the presence of a premature stop codon in the mRNA that initiates mRNA degradation
What are the 2 forms of damage control for mutated genes?
- mRNAs with pre-mature stop codons got degraded: no protein synthesized
- If truncated protein synthesized, it often degrades in ER before delivery to membrane
What is the importance of damage control?
If the truncated protein is not going to function anyway, We better save resources on its synthesis and delivery to proper location. Also, it might possess novel, cell-damaging function.
What are the types point mutations?
frameshift nonsense missense substitution silent
What does regulatory mutations affect?
Affects promoters, or other regulatory sequences of the gene
What are purposes of duffy blood group proteins?
an antigen
a receptor for chemokines
a receptor for Plasmodium vivax malaria parasites
What are some examples of regulatory mutations?
lactose intolerance
Duffy gene
What is prodynorphin locus (PDYN)?
Encodes opioid neuropeptide precursor for endogenous ligands for opiate receptor: balances “pleasure” genes
What does PDYN do?
- mediate the anticipation and experience of pain
- influence social attachment and bonding behaviour
- affect learning and memory
What does PDYN influence?
Schizophrenia
cocaine addiction
epilepsy
What is DARC
A Chemokine receptor that allows people to be resistant to infection with malaria