Cycle 9 - Development and Cancer Flashcards
What are silent mutations?
Mutations where the codon changes but the amino acid produced is the same (redundancy), so there is no obvious effect
What are missense mutations?
Missense mutation occur when a codon changes into another codon that makes another amino acid
- Difficult to predict consequences
What are nonsense mutations?
Nonsense mutations occur when a codon changes into a stop condon, ending translation early
- If it is early in the sequence, it likely will destroy the protein
- If it is at the end, maybe it will have no effect, just some end piece is lost
What are frameshift mutations?
Frameshift mutations are insertion/deletions of a base paur, which changes all the amino acids after it
- Likely to be the most severe
- The protein could be too short; a stop codon could be created due to shifting
- THe protein could be too long; the original stop codon could be lost due to shifting
- However, the splicing of introns/exons would not be affected unless the mutation is inserted directly into the splce signal
State the characteristics that make Drosophila an attractive model system
- Genetic control of pattern formation is well documented in Drosophila and apply to many other species as well as humans
- Development is quick
- A complex multicellular organism
- Cheap to raise
- Similar genome as humans
Describe the main stages of Drosophila embryonic development
- Begins at fertilized egg
- Cell doesn’t divide, the nucleus does (unusual)
- Cellularization (movement to the sides, formation of separate pole cells)
- Gastrulation: segmentation
- Hatches into larvae, then eventually it forms a pupae, and the becomes a fly
Describe the role of maternal effect genes in Drosophila development
Explain Bicoid and Gurken
-
Maternal effect gene: is transcribed in mother but translated in offspring (pack eggs with mRNA and proteins)
- mRNA is stopped from translating via masking proteins which come off when the offspring is ready
- Bicoid (anterior posterior) is an important gene
- Mothers pack one end with bicoid mRNA: lots of bicoid = head region
- Gurken (dorsal ventral) is an important gene
- These genes help orient the nuclei to tell them what genes to express
What are segmentation genes?
Segmentation genes are turned on by bicoid, and divide the embryo into segmeents/stripes
What are homeotic genes?
Homeotic genes are turned on by segmentation genes, and create the proper structure in a sigen segment (ex., legs, wings)
Describe the structure/function of the “homeobox” in homeotic genes
- A homeobox is a 180 bp sequence within the homeotic genes coding for a DNA-binding domain (i.e., it is a transcription factor)
- Transcription factors are proteins that help turn specific genes “on” or “off” by binding to nearby DNA.
- Ex., a homeotic gene in the leg segment is a transcription factor that stimulates expression for leg-specific genes
Describe the significance of evolutionary conservation of Hox genes
- Hox genes are a subset of homeobox genes
- Many organisms have all of their hox genes together in the genome in the same order of which they are expressed
- This shows that it is a very ancient genetic system
Describe the function of caspases
Caspases are proteases; they chop up essential proteins and assist in program cell death
- Describe the path of programmed cell death cascade (C. elegans)
- C. elegans cells are transparent so it is useful to study
- As it develops, 1 cell becomes 959 cells, but 131 cells die as part of normal development using CED genes
- CED genes (cell death genes) are found in every cell and are part of a protein cascade
- The death signal is received by the death signal receptor
- CED-9 is inhibited from blocking CED-4
- CED-4 can activate CED-3
- CED-3 kills the cell by activating proteases and nucleases
- Note that these signals can also be internal (ex., DNA damage of infection can trigger apoptosis)
Describe the role of programmed cell death in Drosophila development
- In drosophila, one genome code for a larva first, and then a fly
- It does this through imaginal discs that sit in the larvae, which expand to create legs and wings when it receives a blast of hormone
- All the unneeded larvae tissue gets destroyed through apoptosis
- Unique Drosophila gene called the reaper, works with the grim protein to trigger cell death
- In the promoter of reaper, there are multiply types of control (pictured)
- p53: when DNA repair is suppresed, the reaper is gene expressed
State the most common cancers in Canada
Why might cancer mortality rates vary across geographical areas in Canada?
- Breast cancer, prostate cancer, colon cancer, lung cancer are most common
- Variation of geographcial mortality due to
- Access to healthcare
- Different genetic populations, age difference, lifestyle difference
- Different environment
Describe cell fate and how a driver mutation can occur
- Firstly, cancer cells are de-differentiated (resemble undifferentiated embryonic cells)
- Cell fate is represented by a landscape
- High topography = instability = cell type will easily change into something different
- Normally development follows the blue line which is barred from changing state by the purple hills (genes that regulate growth)
- The red line is an abnormal trajectory caused by getting over the barrier; “cancer is just another cell fate”
