Lecture 18: WHAT ARE RECESSIVE AND DOMINANT MUTATIONS? Flashcards
When is a mutation a germline mutation?
If a mutation occurs in a cell that go on to make gametes (eggs or sperm), the mutation can be passed on to the next generation (in born errors of metabolism)
Where do somatic mutations occur?
In other cells and cannot be passed on
How many cells is the human body made up of?
Approximately 37 trillion
What does a human cell normally do?
Grow and divide to form new cells as the body needs them (balance and homeostasis)
What happens when cells grow old or become damaged?
They die and new cells take their place
What is cancer?
A collection of related diseases and can start almost anywhere in the body
What are cancer cells?
Cells within a tissue that no longer respond to many of the signals that control cellular growth and death
What happens to cancer cells over time?
They become increasingly resistant to the controls that maintain normal tissue - and as a result they divide more rapidly
What do cancer cells evade?
Programmed cell death despite their multiple abnormalities
What happens in the late stages of cancer?
Cells break through normal tissue boundaries and metastasise (spread) to new sites in the body
What is cancer a result of?
An accumulation of mutations
What are most cancer mutations associated with?
DNA replication
What happens the more times a cell divides?
The more likely it is to gain a mutation - this is why the incidence of cancer is greatly increased with age
How many genes encode proteins that normally regulate cell growth and division?
Hundreds
What can lead to cancer?
Mutations that alter the genes regulating cell growth and division in somatic cells
What may mutations be?
Spontaneous (occur by chance) or the result of exposure to a mutagen (carcinogen) such as smoking or UV radiation
What are the types of genes that cause cancer when mutated?
Tumor suppressor genes and oncogenes
What do tumor suppressor genes encode?
Proteins that normally prevent uncontrolled cell growth
What are examples of tumor suppressor genes?
proteins that inhibit cell division and prevent other mutations (DNA repair enzymes)
What can lack of tumor suppressor genes do?
Stimulate cell growth
What type of mutations occur in tumor suppressor genes?
Recessive
What do oncogenes encode?
Proteins that promote cell growth
What are examples of oncogenes?
Proteins that stimulate cell division. Cancer mutations increase the activity of these genes
What type of mutations occur in oncogenes?
Dominant
What happens to the cell normally?
It is prevented from undergoing cell division, due to E2F transcription factor being bound to RB protein in the cytoplasm
What happens when the signal for cell division is detected by a receptor?
A kinase is activated which adds a phosphate to RB protein. This initiates a conformational change, releasing E2F transcription factor into the nucleus so cell division genes can then be expressed
What does a loss of function get in both copies of the RB gene do?
Cause activation of the E2F transcription factor
What does a loss of function mutation in the p16 gene cause?
Activation of the E2F transcription factor
What is a proto-oncogene?
A normal gene that when mutate can promote uncontrolled cell growth
What do mutations that increase transcription in the promoter region cause?
An excess production of normal growth stimulating protein causing increased cell growth
What do mutations that increase protein activity in the coding region cause?
A protein to always be active or not be degraded causing increased cell growth
What chromosomal changes can cause increased cell growth?
Gene duplications and translocation
What can gene duplications cause?
Increased protein production and cell growth
What is translocation?
When a piece of one chromosome fuses with a piece of another chromosome and can increase cell growth
What is chronic myeloid leukaemia an example of?
How oncogene and tumor suppressor mutations lead to cancer
What happens in chronic myeloid leukaemia?
A break in chromosome 9 fuses with a break in chromosome 22 to form a Philadelphia chromosome where BCR gene infused to ABL gene
What is the ABL gene under control in the Philadelphia chromosome?
The BCR promoter region so it isn’t regulated how it should normally be
What is the oncogene in chronic myeloid leukaemia?
BCR-ABL gene
The new BCR-ABL gene is …
always active
What does the norma BCR-ABL gene need?
A cellular signal to activate it so it can promote cell division
What can the BCR-ABL gene do?
Promote cell division without a signal
What is needed to cause uncontrolled cell division and cancer?
A functional tumor suppressor gene will prevent cancer so mutations in both copies of RB tummy suppressor genes and the oncogene are needed
What do inherited mutations do?
Increase chance of cancer because it is one less mutation which needs to occur
What are the types of cancer treatment?
Surgery, radiation therapy, chemotherapy and target therapy
What happens in surgery?
Cancer cells are removed
What happens in radiation therapy?
Targeted radiation treatment to kill cancer cells
What happens in chemotherapy?
Uses drugs that target dividing cells as cancer cells grow and divide rapidly but it also affects normal cells
What is an example of chemotherapy?
Mercaptopurine
What is Mercaptopurine?
A DNA base analog that inhibits with enzymes that make dATP and dGTP nucleotides needed for cell division
What is used in target therapy?
Drugs that target changes in caner cells that allow them to grow and divide
What is an example of target therapy?
Gleevac
What does Gleevac do?
Inhibits kinase activity of BCR-ABL protein
