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Related Concept Videos

Mismatch Repair

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...

Mismatch Repair

Mismatch Repair

Mismatch Repair

Mismatch Repair

Spontaneous and Induced Mutations

Spontaneous and Induced Mutations

Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).

Single Nucleotide Polymorphisms-SNPs

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...

Point and Frameshift Mutations

Point and Frameshift Mutations

Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...

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Related Experiment Video

Updated: Apr 15, 2026

Rare Event Detection Using Error-corrected DNA and RNA Sequencing

Rare Event Detection Using Error-corrected DNA and RNA Sequencing

Published on: August 3, 2018

Microsatellite instability use in mismatch repair gene sequence variant classification.

Bryony A Thompson^1,2, Amanda B Spurdle³

¹Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Brisbane, QLD 4006, Australia. bryony.thompson@hci.utah.edu.

|April 2, 2015

Summary

Identifying the clinical significance of DNA mismatch repair (MMR) gene variants is crucial for cancer risk assessment. This review explores using microsatellite instability (MSI) in tumors to classify uncertain MMR gene variants, aiding genetic counseling and patient management.

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Last Updated: Apr 15, 2026

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Area of Science:

Genetics
Oncology
Molecular Biology

Background:

Inherited mutations in DNA mismatch repair (MMR) genes increase susceptibility to colorectal and endometrial cancers.
Microsatellite instability (MSI) is the key molecular marker of MMR deficiency.
Accurate classification of MMR gene variants is vital for patient management and genetic counseling.

Purpose of the Study:

To review the role of microsatellite instability (MSI) in classifying sequence variants of uncertain clinical significance in MMR genes.
To discuss considerations for using MSI and tumor characteristics in MMR gene variant interpretation.

Main Methods:

Review of literature on MMR gene variants and MSI.
Analysis of the utility of MSI in determining variant pathogenicity.
Exploration of tumor characteristics for variant classification.

Main Results:

Unclassified MMR gene variants pose challenges in genetic counseling.
MSI status in tumors can assist in classifying the clinical significance of MMR variants.
Careful consideration is needed when applying MSI for variant interpretation.

Conclusions:

MSI testing in tumors is a valuable tool for interpreting uncertain MMR gene variants.
Integrating MSI and other tumor data enhances the accuracy of MMR variant classification.
Improved variant classification facilitates better clinical management and genetic counseling for families at risk of hereditary cancers.