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1 STOCKHOLMS UNIVERSITET Institutionen för biologisk grundutbildning Re-exam in Molecular Biology and Genome Analysis, Name: Birth date: Points:1st part 2nd part Total Grade Time for the exam is kl Write your name on all pages even if the question is not answered!!!! The questions can be answered in Swedish or English. Write your answer directly in the question sheet. Also the back side can be used. Extra paper is available. No material of aid is permitted. Write clearly!!! Unreadable answers will not be considered. The exam has two parts points= 100 points. Lowest level for pass (score E) is 60/100 points. GOOD LUCK!!!
2 Part 1 Multiple choice questions: 1. The degeneracy of the genetic code refers to which of the following? a. Each codon can specify more than one amino acid b. Most amino acids have more than one codon c. There are several initiation codons d. The stop codons can also code for amino acids During which stage of the cell cycle does DNA replication occur? a. M b. G1 c. S d. G A major problem with the computational assembly of DNA sequences of complex eukaryotic genomes is the presence of: a. Multiple chromosomes b. Mitochondrial DNA c. Introns within the genome d. Repetitive sequences Which of the following is the correct definition of synteny? a. The percentage of nucleotide sequence identity between two genomes b. The percentage of amino acid sequence identity between two genomes c. The conservation of gene order within two genomes d. The conservation of gene function within two genomes Why is inactivation a useful technique to determine the function of a gene? a. Gene inactivation provides information about the expression of the gene b. Gene inactivation provides information about the cellular location of a gene product c. Gene inactivation provides an opportunity to identify phenotypic changes associated with the loss of the functional gene d. Gene inactivation provides information on the structure of the gene product 5
3 6. How can two different transcriptomes be studied with a single microarray? a. One transcriptome is hybridized and studied first and then its sequences are removed and the second transcriptome is studied on the same microarray b. Only one of the transcriptomes is labelled and it competes with the second, unlabeled transcriptome for binding to the probe sequences c. The transcriptomes are hybridized to each other prior to the microarray analysis to remove cdnas present from both cell types. d. The two transcriptomes are labelled with different fluorescent probes and hybridized simultaneously What is the centromere of a chromosome? a. It is the end of the chromosome b. It is the uncondensed region of a chromosome that contains active genes c. It is the constricted region of a chromosome where the two copies are held together d. It is the condensed, transcriptionally silent regions of chromosomes De novo methylation of DNA is defined as which of the following? a. The addition of methyl groups to DNA at new positions to change the methylation pattern of the genome b. The addition of methyl groups to newly synthesized strands of DNA to ensure that the daughter strands possess the same methylation patterns as the parent strands. c. The addition of methyl groups to gene promoters to activate gene expression. d. The addition of methyl groups to insulator regions to repress gene expression Which type of modification must be made to RNA polymerase II in order to activate the preinitiation complex? a. Acetylation b. Methylation c. Phosphorylation d. Ubiquitination 9
4 10. Nonsense-mediated RNA decay (NMD) is a system for the degradation of eukaryotic mrna molecules with what features? a. NMD degrades mrna molecules with stop codons at incorrects positions. b. NMD degrades mrna molecules that encode non-functional proteins c. NMD degrades mrna molecules that lack a start codon. d. NMD degrades mrna molecules that lack a stop codon Which of the following describes RNA interference? a. Antisense RNA molecules block the translation of mrna molecules b. Double-stranded RNA molecules are bound by proteins that block their translation c. Doube-stranded RNA molecules are cleaved by a nuclease into short interfering RNA molecules. d. Short interfering RNA molecules bind to the ribosome to prevent the translation of viral mrnas The topological problem of DNA replication refers to which of the following? a. The blockage of DNA replication sites by nucleosomes b. The difficulty of synthesizing DNA on the lagging strand c. The unwinding of the double helix and the rotation of the DNA d. The synchronization of DNA replication with cell division The differences between humans and chimpanzees are most likely due to: a. The presence of extra genes in the human genome. b. The deletion of chimpanzee genes from the human genome. c. Changes in the amino acid sequences of proteins involved in speech. d. Differences between the expression patterns of the two genomes. 13..
5 Short answer questions 14. Yeast artifical chromosomes must have which three features of normal chromosomes to be maintained in cells? (3p) 15. What structural features of functional RNA molecules such as trna and rrna, can be searched for in a genome sequence to identify the genes encoding these RNA molecules? (2p)
6 16. How can the study of homologous genes provide information on human diseases? (2p) 17. What is the role of histone deacetylases (HDACs) in regulation of genome expression? (2p)
7 18. During initiation of transcription in eukaryotes a protein called TBP plays an important role. What is TBP and what is its function? (2p) 19. Why does RNA degradation play an important role in the regulation of genome expression? (2p)
8 20. What is the role of the small nucleolar RNA (snorna) molecules in the modification of eukaryotic pre-rrna molecules? (2p) 21. Why do eukaryotic cells need a telomerase? What types of macromolecules build up the telomerase, and which are their biological functions? (3p)
9 22. What is the difference between a conventional pseudogene and a processed pseudogene in terms of structure and mechanism of origin? (2p) 23. What are the common modifications made to transcripts of protein-coding genes in eukaryotes? (3p)
10 24. What is RNA editing? The answer should include which type of molecules that are edited, a brief description of the mechanism and what the effects can be (4p).
11 Part 2 1. Describe the structure of how DNA is packed within the eukaryotic nucleus. (3p) 2. The human papilloma virus HPV-16 is a DNA virus that lacks DNA polymerase. How does it replicate its DNA genome in the infected cell? Include which functions proteins E1 and E2 plays for this. (3p)
12 3. Deoxyribonucleotides are synthesized by direct reduction of the four ribonucleotides ATP, CTP, GTP and UTP. How is dttp synthesized? (3 p) 4. What are the main cellular targets of bioactive small molecules? (3p)
13 5. Many proteins in our cells have amazingly short half-lives. The majority of these proteins are not damaged and are functioning perfectly. Why do our cells have degradation systems that target newly made proteins? (2p) 6. Why does the transcriptome not provide a completely accurate indication of the proteome of the cell? (2p)
14 7. Give examples of crucial factors that affect the analysis of whole genome duplications (tetraploidizations)! (2p) 8. Briefly describe one advantage and one disadvantage with RNAi-based screens (3p)
15 9. What are entomopathogenic nematodes? (2p) 10. Describe how model systems can be used to assign the function of genes. (3p)
16 (A)What is metagenomics? (B) Briefly describe one study wherein metagenomic methods have been applied. (4p) 11. Describe step-by-step how you would find the mrna sequence for a protein of interest from an organism whose genome hasn't been sequenced? (4p)
17 12. During an experiment you have obtained a suspicious, coding nucleotide sequence. You suspect that it was a contamination brought in by your co-worker who is a cat-fanatic. Describe a suitable strategy to prove your case using computational tools. (4p)
18 13. What are the major similarities and differences between small interfering RNAs (sirna) and micrornas (mirna) in their properties, activities and effects they have on cellular processes? (6p)
19 14. You have isolated a gene from a eukaryotic organism. The gene has not been previously described. You wish to learn about the function of the gene. Briefly describe how you can get experimental information that will help you to formulate a hypothesis about the function of the gene. The answer should include the strategy behind your approach, the methods you would use and the information these methods can give you. (6p)
20 15. Many of the novel approaches used for genome analysis are based on pyrosequencing. (6p) (A) Describe in detail the principles behind pyro-sequencing and how it is carried out. (B) What is it that makes this method much more effective compared to the Sanger method? (C) List three applications for pyrosequencing.
21 16. During this course you have studied a subject and written a short review course. Write a brief description of your subject and summarize the major breakthroughs that have been made in the field the last years. In your mind, what is the most interesting question(s) to continue with in this field of research? (6p)
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