Additional Practice Problems for Reading Period
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1 BS 50 Genetics and Genomics Reading Period Additional Practice Problems for Reading Period Question 1. In patients with a particular type of leukemia, their leukemic B lymphocytes display a translocation between one of the immunoglobulin genes and a gene encoding a cytoplasmic protein kinase. (a) Suggest a basis for the tumorigenic activity of this translocation. (b) In one patient some of the cells containing the translocation have lost their capacity for rapid proliferation. Suggest a type of mutation in the cytoplasmic protein kinase that might have led to this loss of proliferative ability. Question 2. Bloom syndrome is an autosomal recessive disorder that is associated with a high frequency of spontaneous chromosome breakage as a result of a gene defect in DNA replication. Why do you think there is an increased chance of cancer associated with this syndrome?
2 Question 3 (28 points). Below is a list of specific mutations in some genes contributing to regulation of cell numbers: For each of these mutations, state whether this mutation would contribute to tumor formation and briefly justify your answer. For those that would contribute to tumor formation, indicate whether they would act as dominant oncogenes or recessive mutations in tumor suppressor genes. (a) A point mutation that creates a stop codon in place of the codon for the third amino acid in the Ras protein. (b) A translocation that fuses the mrna-coding sequences of an initiator caspase gene to the enhancer element for a gene that is highly expressed in the hepatocyte cells of the liver. (c) A deletion within the protein-coding region that eliminates the extracellular ligand-binding domain of a receptor tyrosine kinase (RTK), thereby permitting the RTK to dimerize in the absence of ligand. (d) A frameshift mutation within the protein-coding sequence of the Rb protein.
3 Question 4 (30 points): Which of the following statements about embryonic pattern formation in Drosophila are true and which are false? Briefly justify each answer. (Assume all mutations are null mutations.) A) An embryo homozygous for a pair-rule mutation exhibits abnormal patterns of segment polarity gene expression. B) An embryo homozygous for a pair-rule mutation exhibits abnormal patterns of gap gene expression. C) One quarter of the embryos produced by parents heterozygous for a null bicoid mutation will exhibit abnormal patterns of gap gene expression. D) One quarter of the embryos produced by parents heterozygous for a null HB-Z mutation will exhibit abnormal patterns of pair-rule gene expression.
4 E) A female homozygous for a gap gene mutation, crossed to wild-type males, produces offspring that have abnormal patterns of segment polarity gene expression. F) A male homozygous for a mutation in the bicoid gene, crossed to wild-type females, produces abnormal patterns of gap gene expression.
5 Question 5. 5a) You have a mutation affecting anterior-posterior patterning of the Drosophila embryo in which every other segment of the developing mutant larva was missing. Is it a mutation in a gap gene, a pair-rule gene, a segment polarity gene, or a segment identity gene? 5b) You have cloned a piece of DNA that contains four genes. How could you use the spatial expression pattern of their mrnas in a wild-type embryo to identify which represents a candidate gene for the mutation described in part a. 5c) Assume you have identified the candidate gene. You now examine the wild-type spatial expression pattern of its mrna in an embryo homozygous mutant for the gap gene Krüppel. Would there be a normal expression pattern? Why or why not?
6 Question 6: You have in your possession wild-type and bicoid mutant Drosophila strains. You also have cloned cdnas for nanos and bicoid. These plasmids are as follows: plasmid 1 plasmid 2 plasmid 3 plasmid 4 plasmid 5 full length nanos cdna full length bicoid cdna bicoid 5 UT + bicoid ORF + nanos 3 UT nanos 5 UT + bicoid ORF + bicoid 3 UT nanos 5 UT + bicoid ORF + nanos 3 UT where UT = untranslated region and ORF = open reading frame (protein coding region) The plasmids are constructed so they are expressed in transgenic animals. You systematically create ten transgenic fruitfly strains by introducing each of the five plasmids into each of wild type and bicoid mutant strains. Then, you look where the bicoid protein is spatially localized in the fly embryo. Complete the following table indicating where bicoid protein is found in each transgenic strain, answering either Anterior, Posterior, Both, or Neither. You may abbreviate A, P, B, or N for your answer. Transgenic Wild Type Transgenic bicoid mutant plasmid 1 plasmid 2 plasmid 3 plasmid 4 plasmid 5
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