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Ch. 15 - Gene Mutation, DNA Repair, and Transposition
Chapter 15, Problem 24

Presented here are hypothetical findings from studies of heterokaryons formed from seven human xeroderma pigmentosum cell strains: XP1 XP2 XP3 XP4 XP5 XP6 XP7 XP1 - XP2 - - XP3 - - - XP4 + + + - XP5 + + + + - XP6 + + + + - - XP7 + + + + - - - Note: + = complementation; - = no complementation These data are measurements of the occurrence or nonoccurrence of unscheduled DNA synthesis in the fused heterokaryon. None of the strains alone shows any unscheduled DNA synthesis. Which strains fall into the same complementation groups? How many different groups are revealed based on these data? What can we conclude about the genetic basis of XP from these data?

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Complementation Testing

Complementation testing is a genetic technique used to determine whether two mutations that produce a similar phenotype are in the same gene or in different genes. In this context, if two strains complement each other (indicated by a '+'), they are likely in different complementation groups, meaning they have mutations in different genes. Conversely, if they do not complement (indicated by a '-'), they are in the same group, suggesting that the mutations affect the same gene.
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Complementation

Heterokaryons

Heterokaryons are cells that contain two or more genetically distinct nuclei within a common cytoplasm, often formed by the fusion of different cell types. In the study of xeroderma pigmentosum (XP), analyzing heterokaryons allows researchers to observe how different genetic mutations interact, particularly in terms of DNA repair mechanisms. The presence or absence of unscheduled DNA synthesis in these cells provides insights into the functionality of the genes involved.

Xeroderma Pigmentosum (XP)

Xeroderma pigmentosum (XP) is a genetic disorder characterized by extreme sensitivity to ultraviolet (UV) light, leading to a high risk of skin cancer. It is caused by mutations in genes responsible for nucleotide excision repair, a critical DNA repair pathway. Understanding the complementation groups in XP strains helps identify which specific genes are defective and how they contribute to the disease's phenotype, thereby elucidating the genetic basis of the disorder.
Related Practice
Textbook Question
In a bacterial culture in which all cells are unable to synthesize leucine (leu⁻), a potent mutagen is added, and the cells are allowed to undergo one round of replication. At that point, samples are taken, a series of dilutions are made, and the cells are plated on either minimal medium or minimal medium containing leucine. The first culture condition (minimal medium) allows the growth of only leu⁺ cells, while the second culture condition (minimal medium with leucine added) allows growth of all cells. The results of the experiment are as follows: Culture Condition Dilution Colonies Minimal medium 10⁻¹ 18 Minimal medium + leucine 10⁻⁷ 9 What is the rate of mutation at the locus associated with leucine biosynthesis?
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Textbook Question

In 2010, a U.S. District Judge ruled to invalidate Myriad Genetics' patents on the BRCA1 and BRCA2 genes. Judge Sweet noted that since the genes are part of the natural world, they are not patentable. Myriad Genetics also holds patents on the development of a direct-to-consumer test for the BRCA1 and BRCA2 genes.

Would you agree with the ruling to invalidate the patenting of the BRCA1 and BRCA2 genes? If you were asked to judge the patenting of the direct-to-consumer test for the BRCA1 and BRCA2 genes, how would you rule?

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Textbook Question

In 2010, a U.S. District Judge ruled to invalidate Myriad Genetics' patents on the BRCA1 and BRCA2 genes. Judge Sweet noted that since the genes are part of the natural world, they are not patentable. Myriad Genetics also holds patents on the development of a direct-to-consumer test for the BRCA1 and BRCA2 genes.

J. Craig Venter has filed a patent application for his 'first-ever human-made life form.' This patent is designed to cover the genome of M. genitalium. Would your ruling for Venter's 'organism' be different from the judge's ruling on patenting of the BRCA1 and BRCA2 genes?

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Textbook Question
Imagine yourself as one of the team of geneticists who launches a study of the genetic effects of high-energy radiation on the surviving Japanese population immediately following the atom bomb attacks at Hiroshima and Nagasaki in 1945. Demonstrate your insights into both chromosomal and gene mutation by outlining a short-term and long-term study that addresses these radiation effects. Be sure to include strategies for considering the effects on both somatic and germ-line tissues.
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Textbook Question
With the knowledge that radiation causes mutations, many assume that human-made forms of radiation are the major contributors to the mutational load in humans. What evidence suggests otherwise?
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Textbook Question
Among Betazoids in the world of Star Trek®, the ability to read minds is under the control of a gene called mindreader (abbreviated mr). Most Betazoids can read minds, but rare recessive mutations in the mr gene result in two alternative phenotypes: delayed-receivers and insensitives. Delayed-receivers have some mind-reading ability but perform the task much more slowly than normal Betazoids. Insensitives cannot read minds at all. Betazoid genes do not have introns, so the gene only contains coding DNA. It is 3332 nucleotides in length, and Betazoids use a four-letter genetic code. The following table shows some data from five unrelated mr mutations. Mutation Description of Mutation Phenotype _ mr-1 Nonsense mutation in codon 829 Delayed-receiver mr-2 Missense mutation in codon 52 Delayed-receiver mr-3 Deletion of nucleotides 83–150 Delayed-receiver mr-4 Missense mutation in codon 192 Insensitive mr-5 Deletion of nucleotides 83–93 Insensitive For each mutation, provide a plausible explanation for why it gives rise to its associated phenotype and not to the other phenotype. For example, hypothesize why the mr-1 nonsense mutation in codon 829 gives rise to the milder delayed-receiver phenotype rather than the more severe insensitive phenotype. Then repeat this type of analysis for the other mutations. (More than one explanation is possible, so be creative within plausible bounds!)
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