Ssp

A researcher has already isolated cDNA for runtase and has sequenced it, but the location of the runtase gene in the Drosophila genome is unknown.

In attempting to devise a strategy for turning off the production of SSP and producing giant flies by using standard recombinant DNA techniques, you discover that deleting, inactivating, or otherwise mutating this DNA sequence in Drosophila turns out to be extremely difficult. Therefore you must restrict your genetic engineering to gene augmentation (adding new genes to cells). Describe the methods that you will use to turn off SSP and produce giant flies by using recombinant DNA technology.

42. A rare form of polydactyly (extra fingers and toes) in humans is due to an X-linked recessive gene, whose chromosomal location is unknown. Suppose a geneticist studies the family whose pedigree is shown here. She isolates DNA from each member of this family, cuts the DNA with a restriction enzyme, separates the resulting fragments by gel electrophoresis, and transfers the DNA to nitrocellulose by Southern blotting. She then hybridizes the nitrocellulose with a cloned DNA sequence that comes from the X chromosome. The pattern of bands that appear on the autoradiograph is shown below each person in the pedigree.

(a) For each person in the pedigree, give his or her genotype for RFLPs revealed by the probe. (Remember that males are hemizygous for X-linked genes, and females can be homozygous or heterozygous.)

(b) Is there evidence for close linkage between the probe sequence and the X-linked gene for polydactyly? Explain your reasoning.

(c) How many of the daughters in the pedigree are likely to be carriers of X-linked polydactyly? Explain your reasoning.

SUGGESTED READINGS)_

Andrews, L. B., J. E. Fullarton, N. A. Holtzman, and A.G. Molulsky. 1994. Assessing Genetic Risks: Implications for Health and Social Policy. Washington, DC: National Academy Press. Discusses some of the legal, ethical, and social issues surrounding gene testing. Berg, P., D. Baltimore, H. W. Boyer, S. N. Cohen, R. W. Davis, D. S. Hogness, D. Nathans, R. Roblin, J. D. Watson, S. Weissman, and N. D. Zinder. 1974. Potential biohazards of recombinant DNA molecules. Science 185:303. Well-known letter calling for a moratorium on certain types of recombinant DNA experiments.

Cohen, J. S., and M. E. Hogan. 1994. The new genetic medicine. Scientific American 271(6):76-82. A good review of oligonucleotide drugs. Cohen, S., A. Chang, H. Boyer, and R. Helling. 1973. Construction of biologically functional bacterial plasmids in vitro. Proceedings of the National Academy of Sciences of the United States of America 70:3240 - 3244. Description of the first gene-cloning experiments. Enriquez, J. 1998. Genomics and the world's economy. Science 281:925-926.

Discussion of the growing importance of gene sequencing and biotechnology in the world economy.

Friedmann, T. 1997. Overcoming the obstacles to gene therapy. Scientific American 276(6):96-101. Review of some of the current problems in gene therapy. Gasser, C. S., and R. T. Fraley. 1992. Transgenic crops. Scientific American 266(6):62-69.

An excellent and readable account of how genes are put into plants and some of the applications. Isner, J. M. 2002. Myocardial gene therapy. Nature 415:234-239. Discusses recent research on the use of gene therapy to treat coronary artery disease and heart failure.

Mullis, K. B. 1990. The unusual origin of the polymerase chain reaction. Scientific American 262(4):56-65. Mullis describes his inspiration for the polymerase chain reaction.

Nowak, R. 1994. Forensic DNA goes to court with O. J. Science 265:1352 -1354.

A report on the use of DNA fingerprinting in the famed O. J. Simpson trial.

Roberts, L. 1992. Science in court: a culture clash. Science 257:732-736.

A report on some of the controversy surrounding DNA fingerprinting.

Salo, W. L., A. C. Aufderheide, J. Buikstra, and T. A. Holcomb. 1994. Identification of Mycobacterium tuberculosis DNA in a pre-Columbian Peruvian mummy.

Proceedings of the National Academy of Sciences of the United States of America 91:2091 - 2094.

Report of tuberculosis-causing bacteria in a 1000-year-old Peruvian mummy.

Stein, C. A., and Y. C. Cheng. 1993. Antisense oligonucleotides as therapeutic agents: is the bullet really magical? Science 261:1004 -1011.

A review of the development of oligonucleotide drugs.

Verma, I. M., and J. Somia. 1997. Gene therapy: promises, problems, and prospects. Nature 389:239 -242. A good review of the state of gene therapy.

Wofenbarger, L. L., and P. R. Phifer. 2000. The ecological risks and benefits of genetically engineered plants. Science 290:2088-2093.

A review of scientific evidence of benefits and risks associated with the use of genetically engineered organisms in agriculture.

Yan, H., K. W. Kinzler, and B. Vogelstein. 2000. Genetic testing: present and future. Science 289:1890-1892. A review of some of the problems associated with genetic testing and current techniques being developed to overcome them.

Zanjani, E. D., and W. F. Anderson. 1999. Prospects for in utero human therapy. Science 285:2084-2088. A review of the potential use of gene therapy in utero on unborn fetuses to correct human genetic defects.

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