If a base-pair change occurs in DNA, this a. is a mutation. b. would be a mutation only if it falls in a protein-coding part of a gene. c. would be a mutation only if it falls in a transcribed part of the genome. d. is not a mutation, because only one base pair has been altered.
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15. Gene Expression
Mutations
Problem 6
Textbook Question
Imagine discovering a loss-of-function mutation in a eukaryotic gene. You determine the gene's nucleotide sequence from the start site for transcription to the termination point of transcription and find no differences from the wild-type sequence. Explain where you think the mutation might be and how the mutation might be acting.

1
Consider the possibility that the mutation is located in a regulatory region rather than within the coding sequence itself. Regulatory regions include promoters, enhancers, and silencers, which control the expression of the gene.
Examine the promoter region, which is upstream of the transcription start site. A mutation here could affect the binding of transcription factors or RNA polymerase, leading to reduced or abolished transcription.
Investigate the enhancer regions, which can be located far from the gene they regulate. A mutation in an enhancer could disrupt the binding of activator proteins, reducing the gene's expression levels.
Consider the possibility of a mutation in the splice sites or intronic regions. Such mutations could lead to improper splicing of the pre-mRNA, resulting in a non-functional protein product.
Explore the potential for epigenetic changes, such as DNA methylation or histone modification, which could silence the gene without altering the nucleotide sequence. These changes can affect chromatin structure and gene accessibility.

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Key Concepts
Here are the essential concepts you must grasp in order to answer the question correctly.
Gene Expression Regulation
Gene expression regulation involves controlling the timing, location, and amount of a gene's product being produced. In eukaryotes, this regulation can occur at multiple levels, including transcription, RNA processing, and translation. Mutations affecting regulatory elements, such as promoters or enhancers, can lead to loss-of-function by altering the gene's expression without changing the coding sequence.
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Non-coding Regions
Non-coding regions of DNA, such as introns, promoters, and enhancers, play crucial roles in gene regulation. Mutations in these areas can affect gene function by disrupting the normal regulatory processes, even if the coding sequence remains unchanged. These mutations can impact transcription factor binding, RNA splicing, or other regulatory mechanisms, leading to altered gene expression.
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Post-transcriptional Modifications
Post-transcriptional modifications include processes like RNA splicing, editing, and transport, which are essential for producing functional mRNA. Mutations affecting these processes can result in loss-of-function by producing defective mRNA or preventing its proper translation. Such mutations might not alter the nucleotide sequence but can disrupt the normal maturation and function of the mRNA.
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