Chromosomal Genetics II Flashcards
Why are most cancers described as Clonal?
All the cancer cells contain the same genetic changes co can be traced back to the single mutated cell.
How can a Deletion cause cancer?
Deletion of Tumour Suppressor genes
How can Duplication cause cancer?
Duplication of Proto- Oncogenes
What are Proto-Oncogenes?
A family signalling molecules responsible for cell division activation and acceleration.
How can Translocations cause cancer?
Position Effect Variegation- cancer is initiated because gene controlling cell division is translocated and inactivated is caused.
Give an example of how Translocation can cause cancer
Burkitt’s Lymphoma- proto-oncogene C-MYC on C8 is moved to C14 next to gene controlling expression of antibodies in B-cells. C-MYC is more heavily expressed as it’s now in a highly transcribed region. Leads to uncontrolled mitosis of B-cells.
What is meant by Aneuploidy?
Individuals with chromosome numbers different from that of the normal number of their species.
What is the main cause of Aneuploidy?
Non-disjunction: a failure in the separation of homologous chromosomes at cell division.
Give an example of an Aneuploidy.
Down’s Syndrome- Trisomy 21 (3 C21). 88% cases caused by nondisjunction of maternal C21.
What is Klinefelter Syndrome an example of?
Aneuploidy- wrong numbers of sex chromosomes (usually extra). Usually compensated by Lyonization.
What is Turner’s Syndrome an example of?
Aneuploidy- only one X chromosome. Person is still female but sterile .
Define Polyploidization
Changes in the number of chromosome sets. Lethal in humans important in agriculture.
What is the difference between an Autopolyploid and an Allopolyploid
Auto- multiplication of number of sets WITHIN a species
Allo- hybridisation of species and mixing of chromosome sets.
What is the importance of Colchicine in Agriculture?
Increases the frequency of polyploidization. Odd number ploids can be made to be sterile (seedless grapes)
What is meant by the term Linkage
The principle that particular loci tend to accompany each other down the generations- the extent to which they do so varies on genes involved.
Outline the Experiments of Bateson and Punnet
- Dihybrid Crosses purple dominant peas and long dominant grains
- PP LL x pp ll
- F1 = Pp Ll purple long
- F2 = Recombinant deficiency (pp LL, PP ll) Excess in parental types (PP LL, pp ll)
Outline the main problems using the Mendel design of cross in linkage analysis.
- Phenotypically identical classes can be disguised as genetically the same
- Statistically Inefficient to study recombinants
Explain the principles of Morgan’s Back Cross.
WT female crossed with mutant male to make F1. Het females of F1 crossed with mutant male to make F2.
What is the expected ratios of the Dihybrid Back Cross for the four genotypes?
1 : 1 : 1 : 1
What was Morgan’s Hypothesis?
The deviation from Mendel’s 2nd is due to physical association (proximity) of loci in either parent - loci on the same pair of homologous chromosomes are linked.
Why is linkage incomplete?
Due to crossing over during meiosis, loci on same chromosome may be separated and recombination may still occur.
Name 5 stages involved in Chiasma Formation during Prophase I
Leptotene, Zygotene, Pachytene, Diplotene and Diakinesis.
Outline the events that occur in Leptotene, Zygotene and Pachytene.
Leptotene - chromosomes become visible.
Zygotene - Homologous chromosome pair up and zip up, synapsis
Pachytene - the pairs get short and fat forming tetrads
What occurs during Diplotene?
The tetrads open out and exchange material forming chiasmata. Occurs between any non-sister chromatids.
What occurs during Diakinesis?
The contraction of chromosomes and movement toward the metaphase plate.
Why can the frequency of recombination never rise above 50%?
For unlinked loci, the ration 1: 1: 1: 1 will hold in the Back Cross, hence 2 out of 4 classes will be recombinants.
What does a recombination frequency of less than 50% suggest?
Linkage- the two genes are likely to be on the same chromosome.
What was the suggestion of Sturtevant?
Variation of recombinant frequency was dependent on the distance apart of the loci in a frequency
What is the equation for Recombination Frequency?
Recombinants/ Total
What will increase the chance of loci being split by chiasma formation?
A larger distance between loci.
Name 3 analytical techniques used in chromosome mapping.
GIEMSA, FISH and Somatic Cell Hybridisation.
How can Giemsa staining be used to map chromosomes?
Giemsa preferentially stains A-T heterochromatic regions (tend to be non coding). The coding G-C rich regions are less condensed and less stained
What does FISH stand for?
Fluorescent In Situ Hybridisation
What is FISH used to localize?
Used to localize the presence or absence of specific DNA sequences on chromosomes
How does FISH work?
- Complementary sequence to target is constructed (probe)
- Probe is attached to biotin-avidin and a fluorophore. If sequence is present, probe will bind and light up.
Outline the principles of Somatic Cell Hybridisation.
- Human cells are fused with mouse cells.
- Human chromosomes are spat out of hybrid cells
- Missing characteristics are associated with genes on missing chromosomes
How are Mouse and Human cells made to fuse?
Sendai Virus- an RNA virus can bind to both human and mice cells simultaneously. As it inserts RNA into both cells they are brought together and forced to fuse.
How is the Sendai virus able to bind to both human and mice cells simultaneously?
The Sendai virus has several points of attachment.
