Mutations in disease and cancer: Revision session topics Flashcards
What is the current definition of a gene?
A segment of a chromosome that produces a functional product
Some genes make RNA that is not translated but is functionally active
List the old definitions of a gene
The basis of inheritable traits
Certain regions of chromosomes
A segment of a chromosome that produces one enzyme
A segment of a chromosome that produces one protein
Mutations occurring in the germ cells are?
Heritable meaning they may lead to a genetic disease in the offspring
Define Somatic mutations
They occur in some random cell in your body
Mutations occurring in the somatic or body cells are not inherited
What types of mutations can lead to tumour formation?
Mutations which interfere with normal cell differentiation and/or proliferation can lead to tumour formation
Define Gross mutations
Gain or loss of whole proteins
List different Gross mutations
Trisomy 18 (47 XY +18): Edwards syndrome
45X: Turners syndrome
Trisomy 13 (47 XY +13) Patau’s syndrome
Translocation: Balanced and unbalanced
How do you write a Karyotype?
47: Number of chromosomes
XY type
+13 Extra chromosome
Define Translocation
Bits of chromosome stick on wrong place
When divided it becomes unbalanced translocation
unbalanced translocation can lead to problems with cell proliferation and control
Can help with understanding genotypes and phenotypes of disease
What can base insertion or deletion result in?
Single base frameshift mutation
What can frameshift lead too?
Lead to either truncated protein or loss of the aberrant transcript through a surveillance process called nonsense-mediated decay.
The part of the protein c-terminal to the site of the mutation is changed extensively
Frameshift results in?
Part of protein is translocated -> c-terminal to the site of the terminal is changed extensively
Define Nonsense mutation
Single base change
Replaces a codon specifying an amino acid with a stop codon ( “x” )
e.g TAC -> TAA
What are the stop codons?
TAA, TAG and TGA
What does truncating mutation cause?
Shortening of the amino acid chain
Nonsense-mediated decay often prevents?
The formation of truncated proteins by degrading Nonsense mRNA, preventing the build-up of crappy proteins
What is the job of Cystic fibrosis Transmembrane Conductance regulator?
Main chloride channel in epithelia of various tissues
Epithelia perform diverse functions such as?
1) water or volume-absorbing (airways and intestinal tract).
2) Salt-absorbing (Sweat, duct, lung).
3) Water or volume - secretory (pancreas, lung). All process involves chloride ion transport disruption that this transport in cystic fibrosis leads to multiple effects
Define the Heterogeneity of DNA mutations
The occurrence of different mutations within the same gene gives a different phenotype
May have a very different effect on the function of the encoded protein
Often a spectrum of severity from very severe to relatively mild, giving a variation in the clinical phenotype.
May allow a genotype-phenotype correlation, to be made. Relates the type of mutation to the disease severity or prognosis
Give an example of a genotype-phenotype correlation
Different mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein
What makes up a Eukaryotic gene?
Promoters
Exons
Introns
Enhancers: enhances transcription factor binding
What happens if a mutation occurs in the promoter region?
Transcription factors less well
RNA polymerase recruitment decrease
Making less mRNA, down express the resulting protein
some mutations can do the opposite
What causes Li-Fraumeni syndrome?
Cause by germline mutations, every cell in your body has one mutated copy in p53
Age will introduce mutation in other copy
p53 can’t regulate cells
Explain Knudons two light hypothesis
Early-onset cancer: Individual with an inherited mutation in a tumour suppressor gene leading to a frequent occurrence of the second event such as gross chromosomal change.
Late-life onset: Normal individual with no mutation on the gene, eventually leads to a very rare first event mutation leading to a frequent second event.
What are Retinoblastoma and Li Fraumeni syndrome?
Autosomal dominant cancer symptom found on autosome gene
What causes Retinoblastoma and Li Fraumeni syndrome
The inheritance of a single mutation from either the p53 or RBgene
Patients develop multiple cancer early in life because the second copy of the gene inactivated by random mutation
In healthy individuals, cancer is later in life commonly associated with loss of both copies of this gene, observation support Knudson’s two-hit hypothesis of cancer development
Define a small scale and single base point mutation?
- A point mutation changes a single DNA base
* Base substitutions
What are the types of small scale and single base (point) mutations?
Transition: Purine (A or G) -> Purine
Pyrimidine (C or T) -> Pyrimidine
T-> C C->T A->G G->A
Transversion: Purine -> Pyrimidine
Pyrimidine -> Purine
T->G T->A C->G C->A A->T A->C G->T G->C
