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Related Concept Videos

Mismatch Repair01:20

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 Repair01:36

Mismatch Repair

Overview
Mismatch Repair01:36

Mismatch Repair

Overview
Mutations01:39

Mutations

Overview
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Spontaneous and Induced Mutations01:30

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).

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Related Experiment Video

Updated: Jun 1, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

An American founder mutation in MLH1.

Jerneja Tomsic1, Sandya Liyanarachchi, Heather Hampel

  • 1Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.

International Journal of Cancer
|June 15, 2011
PubMed
Summary
This summary is machine-generated.

A specific MLH1 gene mutation causes Lynch syndrome (LS), a hereditary cancer risk. This mutation, found in US and Italian Lynch syndrome cases, highlights the need for targeted genetic screening in cancer diagnostics.

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Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
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Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells

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Last Updated: Jun 1, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells
11:06

Identifying DNA Mutations in Purified Hematopoietic Stem/Progenitor Cells

Published on: February 24, 2014

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Lynch syndrome (LS) is an inherited disorder linked to mismatch repair gene mutations, significantly increasing cancer risk.
  • A specific splice site mutation in the MLH1 gene (c.589-2A>G) was identified in unrelated American families with LS.
  • The prevalence and geographic distribution of this MLH1 mutation require further investigation.

Purpose of the Study:

  • To determine the frequency of the MLH1 c.589-2A>G splice site mutation in Lynch syndrome patient cohorts from the Mayo Clinic, Germany, and Italy.
  • To investigate the haplotype associations of this mutation in different populations.
  • To estimate the origin and prevalence of the MLH1 V716M variant.

Main Methods:

  • Analysis of LS cases from diagnostic laboratories and consortia (Mayo Clinic, German HNPCC, Italy).
  • Haplotype analysis to identify shared genetic backgrounds for the MLH1 mutation and V716M variant.
  • Phylogenetic analysis to estimate the age of the V716M variant.

Main Results:

  • The MLH1 c.589-2A>G mutation was found in 1.0% (10/995) of LS mutation carriers at the Mayo Clinic.
  • The mutation was absent in the German HNPCC cohort (0/1,803) but present in 8 individuals from Italy.
  • In the US, the mutation is linked to a large haplotype also carrying the V716M variant; in Italy, it's on a different, shorter haplotype.
  • The V716M variant, found independently, arose approximately 5,600 years ago.
  • The US splice site mutation is estimated to have arisen ~450 years ago and accounts for 1.0% of US LS cases.

Conclusions:

  • The MLH1 c.589-2A>G splice site mutation is a recurrent cause of Lynch syndrome in specific populations, particularly in the United States.
  • Haplotype analysis reveals distinct origins and introductions of this mutation in the US and Italy.
  • The findings support the utility of screening for this specific MLH1 mutation for improved Lynch syndrome diagnosis and risk assessment.