Mutation is the change in the DNA base pair sequence. It can happen due to environmental factors or mistakes in DNA replications. Loss of function and gain of function mutation are two different types of mutations.
The key difference between gain of function and loss of function mutation is their effect. When a gain of function mutation is expressed, it produces a more active gene product, while when a loss of function mutation is expressed, it produces a gene product having less or no functions.
CONTENTS
1. Overview and Key Difference
2. What is Gain of Function Mutation
3. What is Loss of Function Mutation
4. Similarities – Gain of Function and Loss of Function Mutation
5. Gain of Function vs Loss of Function Mutation in Tabular Form
6. Summary – Gain of Function vs Loss of Function Mutation
7. FAQ – Gain of Function and Loss of Function Mutation
What is Gain of Function Mutation?
Gain of function mutation is a type of mutation in a gene that produces a more active gene product (protein). This type of mutation causes the appearance of a new trait or function in inappropriate tissues or at inappropriate times. For example, a mutation in a gene that encodes for a receptor might cause the mutated receptor to stimulate the growth all the time, even in the absence of the growth factor.
Gain of function mutations are frequently dominant in their expression. One good example is Huntington’s disease. Here, a gain-of-function mutation in the HTT gene leads to the production of an abnormal huntingtin protein, which accumulates and causes damage to neurons. Another example is proto-oncogenes, which are activated through gain-of-function mutations.
What is Loss of Function Mutation?
Loss of function mutation is also known as inactivating mutations. Loss of function mutation results in gene product (protein) having less or no functions. Therefore, the gene product will be partially or wholly inactivated by such kind of mutation.
Loss of function mutation is a type of mutation that alters the structure of the protein. Due to the structural change, the resulting protein will no longer work correctly. Moreover, loss of function mutation can also occur in the regulatory region of the protein, affecting transcription, translation, and splicing of the protein. Furthermore, loss of function mutations are frequently recessive. One good example is tumor suppressors, which are inactivated by loss-of-function mutations. In addition, mutations that cause cystic fibrosis disease also cause loss of function mutations, which results in the production of non-functional cystic fibrosis transmembrane regulatory protein. This protein normally regulates the movement of chloride ions into and out of the cell.
Similarities Between Gain of Function and Loss of Function Mutation
- Loss of function and gain of function mutation are two different types of mutations.
- Both affect the expression of the protein.
- They lead to a change in the structure of the gene product (protein).
- Both cause different diseases.
Difference Between Gain of Function and Loss of Function Mutation
Definition
- A gain of function mutation is a mutation that results in a more active protein or acquisition of a different function.
- A loss of function mutation is a mutation that results in an inactive or less active protein.
Prominence
- Gain of function mutations are less prominent mutations.
- Loss of function mutations are more prominent mutations.
Type
- Gain of function mutations are frequently dominant in their expression.
- Loss of function mutations are frequently recessive in their expression.
Examples
- A gain-of-function mutation in the HTT gene causes Huntington’s disease. Another example is the activation of proto-oncogenes through gain-of-function mutations, which can result in uncontrolled cell division.
- Loss-of-function mutations in tumor suppressor genes, such as the TP53 gene, can impair the gene’s ability to regulate cell growth and division, thereby increasing the risk of cancer. In cystic fibrosis, loss-of-function mutations in the CFTR gene lead to the production of a non-functional cystic fibrosis transmembrane conductance regulator protein.
The following table summarizes the difference between gain of function and loss of function mutation.
Summary – Gain of Function vs Loss of Function Mutation
Mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Loss of function and gain of function mutation are two different types of mutations. Gain of function mutation results in a more active protein or acquisition of a different function. Loss of function mutation produces an inactive or less active protein while. Furthermore, loss of function mutations are frequently recessive in their expression, whereas gain of function mutations are frequently dominant in their expression. This is the summary of the difference between gain of function and loss of function mutation.
FAQ: Gain of Function and Loss of Function Mutation
1. What is an example of a loss-of-function mutation disease?
- Spinal muscular atrophy type I (SMA 1) is one of the most frequent genetic diseases. It is caused by mutations in the SMN. It can be considered a loss-of-function mutation disease since it results in a reduction of functional SMN protein.
2. Why are loss-of-function mutations more common?
- Loss-of-function mutations more common because redundant genes within larger gene families are more likely to gain loss of function mutations due to the presence of paralogs that buffer their functional effects.
3. What is a gain-of-function mutation allele?
- Any heterozygote containing the new allele along with the original wild type allele will express the new allele in the gain of function mutation and this allele is known as the gain-of-function mutation allele. Genetically, this will define the mutation as dominant.
4. What is an example of gain of function mutation in humans?
- Most gene mutations identified in patients with hematological malignancies are gain of function mutations. For example, in IDH1/2 mutation, it gains a new function to convert α-KG to 2-HG, leading to the inhibition of TET2 as well as some histone demethylase. This increases the risk of myelodysplastic syndromes (MDS).
Reference:
1. Mair, Barbara, et al. “Gain- and Loss-of-Function Mutations in the Breast Cancer Gene GATA3 Result in Differential Drug Sensitivity.” PLOS Genetics, Public Library of Science.
2. “Gain-of-Function Mutation.” ScienceDirect.
Image Courtesy:
1. “Oncogene and tumour suppressor gene” By Philippe Hupé – Emmanuel Barillot, Laurence Calzone, Philippe Hupé, Jean-Philippe Vert, Andrei Zinovyev, Computational Systems Biology of Cancer Chapman & Hall/CRC Mathematical & Computational Biology (CC BY-SA 3.0) via Commons Wikimedia
2. “Inheritance of a germline loss-of-function mutation in a TSG dramatically increases the risk of cancer” By WassermanLab – Own work (CC BY-SA 4.0) via Commons Wikimedia
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