Genome Mapping Reading Assignment and Study Questions
Not to be handed in!!
5. Mapping Genomes
Learning outcomes
When you have read Chapter 5, you should be able to:
· Explain why a map is an important aid to genome sequencing
· Distinguish between the terms 'genetic map' and 'physical map'
· Describe the different types of marker used to construct genetic maps, and state how each type of marker is scored
· Summarize the principles of inheritance as discovered by Mendel, and show how subsequent genetic research led to the development of linkage analysis
· Explain how linkage analysis is used to construct genetic maps, giving details of how the analysis is carried out in various types of organism, including humans and bacteria
· State the limitations of genetic mapping
Sections 5.2.3 & 5.2.4 Fig 5.1, 5.2, 5.3, 5.12-17, 5.19, 5.21 & 22 Box 5.2
· Self study questions
1. Explain why a map is a useful aid to genome sequencing.
2. Distinguish between 'genetic mapping' and 'physical mapping'. What are the strengths and weaknesses of the two techniques?
3. Why are genes not ideal markers for construction of a genetic map?
4. Describe the various types of DNA marker that are used in genetic mapping. How is each type of marker scored?
5. Refer to Figure 5.5A . Draw the appearance of the autoradiograph if the probe hybridized to a region of DNA entirely between restriction sites R1 and R2. Would detection of the RFLP still be unambiguous?
6. Explain how Mendel's work led eventually to a method for genetic mapping.
7. Draw diagrams of the key events occurring during (a) mitosis, and (b) meiosis. Annotate your diagrams to highlight the important differences between the two processes.
8. Define the term 'partial linkage' and show how partial linkage is the basis of genetic mapping.
9. Describe how linkage analysis is carried out with (a) mice, (b) humans, and (c) bacteria.
10. What factors are responsible for the inaccuracies that sometimes occur in a genetic map?
Learning Outcomes
· Evaluate the strengths and weaknesses of the various methods used to construct physical maps of genomes
· Describe how restriction mapping is carried out
· Describe how fluorescent in situ hybridization (FISH) is used to construct a physical map, including the modifications used to increase the sensitivity of this technique
· Explain the basis of sequence tagged site (STS) mapping, and list the various DNA sequences that can be used as STSs
· Describe how radiation hybrids and clone libraries are used in STS mapping
Study Questions
11. Explain how a restriction map is obtained. What special procedures can be used to increase the size of DNA molecule for which a restriction map can be obtained?
12. What is FISH and how is it used to construct a physical map?
13. Describe the various types of DNA sequence that can be used in STS mapping.
14. Draw a diagram showing how a double-stranded cDNA is synthesized.
15. Define the term 'mapping reagent' and explain how a panel of radiation hybrids is used as a mapping reagent.
16. Explain how a clone library is used as a mapping reagent.
17. Draw a diagram to show how a sample of a single human chromosome can be obtained by flow cytometry.