A genetics counselor, Nashaly Montez, notices an odd pattern in Devin’s pedigree, a propensity for cancer development in his family at a higher incidence in males compared to females. This suggests to Nashaly an X-linked recessive disorder that is not manifesting in females as frequently compared to males who only have one X chromosome. She brings this to the attention of Devin’s primary health care provider who has his client checked for common cancer-causing mutations. A mutant LOF Fox3 regulatory allele is found that has an early NONSENSE codon that prevents protein expression. This is unfortunate, since in its wildtype form the protein is normally tumor-suppressing. 1) Eukaryotic cells will often use polyubiquitination to target mutant proteins to the 26S proteasome for degradation. Would this help address Devin’s LOF problem with his mutant Fox3 allele? a YES! It would keep the mutant protein from being expressed. b YES! It will keep the expressed mutant protein from being able to interact with tumors. c NO! It will keep the expressed protein from being able to interact with tumors. d The mutant Fox3 is a LOF mutation so it is not being expressed. There is nothing for the ubiquitin tags to bind to in this instance. 2)

Human Heredity: Principles and Issues (MindTap Course List)

11th Edition

ISBN:9781305251052

Author:Michael Cummings

Publisher:Michael Cummings

Chapter12: Genes And Cancer

Section: Chapter Questions

Problem 3CS: Mike was referred for genetic counseling because he was concerned about his extensive family history...

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A genetics counselor, Nashaly Montez, notices an odd pattern in Devin’s pedigree, a propensity for cancer development in his family at a higher incidence in males compared to females. This suggests to Nashaly an X-linked recessive disorder that is not manifesting in females as frequently compared to males who only have one X chromosome. She brings this to the attention of Devin’s primary health care provider who has his client checked for common cancer-causing mutations. A mutant LOF Fox3 regulatory allele is found that has an early NONSENSE codon that prevents protein expression. This is unfortunate, since in its wildtype form the protein is normally tumor-suppressing.

Eukaryotic cells will often use polyubiquitination to target mutant proteins to the 26S proteasome for degradation. Would this help address Devin’s LOF problem with his mutant Fox3 allele?

YES! It would keep the mutant protein from being expressed.

YES! It will keep the expressed mutant protein from being able to interact with tumors.

NO! It will keep the expressed protein from being able to interact with tumors.

The mutant Fox3 is a LOF mutation so it is not being expressed. There is nothing for the ubiquitin tags to bind to in this instance.

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