Mutations in disease and cancer: Revision session topics

Question 1

What is the current definition of a gene?

Answer 1

A segment of a chromosome that produces a functional product

Some genes make RNA that is not translated but is functionally active

Question 2

List the old definitions of a gene

Answer 2

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

Question 3

Mutations occurring in the germ cells are?

Answer 3

Heritable meaning they may lead to a genetic disease in the offspring

Question 4

Define Somatic mutations

Answer 4

They occur in some random cell in your body

Mutations occurring in the somatic or body cells are not inherited

Question 5

What types of mutations can lead to tumour formation?

Answer 5

Mutations which interfere with normal cell differentiation and/or proliferation can lead to tumour formation

Question 6

Define Gross mutations

Answer 6

Gain or loss of whole proteins

Question 7

List different Gross mutations

Answer 7

Trisomy 18 (47 XY +18): Edwards syndrome

45X: Turners syndrome

Trisomy 13 (47 XY +13) Patau’s syndrome

Translocation: Balanced and unbalanced

Question 8

How do you write a Karyotype?

Answer 8

47: Number of chromosomes

XY type

+13 Extra chromosome

Question 9

Define Translocation

Answer 9

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

Question 10

What can base insertion or deletion result in?

Answer 10

Single base frameshift mutation

Question 11

What can frameshift lead too?

Answer 11

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

Question 12

Frameshift results in?

Answer 12

Part of protein is translocated -> c-terminal to the site of the terminal is changed extensively

Question 13

Define Nonsense mutation

Answer 13

Single base change

Replaces a codon specifying an amino acid with a stop codon ( “x” )

e.g TAC -> TAA

Question 14

What are the stop codons?

Answer 14

TAA, TAG and TGA

Question 15

What does truncating mutation cause?

Answer 15

Shortening of the amino acid chain

Question 16

Nonsense-mediated decay often prevents?

Answer 16

The formation of truncated proteins by degrading Nonsense mRNA, preventing the build-up of crappy proteins

Question 17

What is the job of Cystic fibrosis Transmembrane Conductance regulator?

Answer 17

Main chloride channel in epithelia of various tissues

Question 18

Epithelia perform diverse functions such as?

Answer 18

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

Question 19

Define the Heterogeneity of DNA mutations

Answer 19

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

Question 20

Give an example of a genotype-phenotype correlation

Answer 20

Different mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) protein

Question 21

What makes up a Eukaryotic gene?

Answer 21

Promoters
Exons
Introns
Enhancers: enhances transcription factor binding

Question 22

What happens if a mutation occurs in the promoter region?

Answer 22

Transcription factors less well
RNA polymerase recruitment decrease
Making less mRNA, down express the resulting protein
some mutations can do the opposite

Question 23

What causes Li-Fraumeni syndrome?

Answer 23

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

Question 24

Explain Knudons two light hypothesis

Answer 24

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.

Question 25

What are Retinoblastoma and Li Fraumeni syndrome?

Answer 25

Autosomal dominant cancer symptom found on autosome gene

Question 26

What causes Retinoblastoma and Li Fraumeni syndrome

Answer 26

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

Question 27

Define a small scale and single base point mutation?

Answer 27

• A point mutation changes a single DNA base

* Base substitutions

Question 28

What are the types of small scale and single base (point) mutations?

Answer 28

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