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Mismatch Repair01:20

Mismatch Repair

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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.
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In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
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A population is composed of members of the same species that simultaneously live and interact in the same area. When individuals in a population breed, they pass down their genes to their offspring. Many of these genes are polymorphic, meaning that they occur in multiple variants. Such variations of a gene are referred to as alleles. The collective set of all the alleles within a population is known as the gene pool.
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Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
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Following the Dynamics of Structural Variants in Experimentally Evolved Populations
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Implementing Mutational Epidemiology on a Global Scale: Lessons from Mutographs.

Michael R Stratton1, Laura Humphreys1, Ludmil B Alexandrov2,3,4

  • 1Cancer, Ageing and Somatic Mutation Programme, Wellcome Sanger Institute, Hinxton, United Kingdom.

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The Mutographs Cancer Grand Challenge uncovered new cancer causes using mutational epidemiology. This research identified unknown environmental exposures and revealed how carcinogens may impact tissue selection, not just DNA.

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Area of Science:

  • Cancer Research
  • Epidemiology
  • Genomics

Background:

  • Cancer's etiology remains incompletely understood.
  • Identifying novel carcinogens and exposure pathways is crucial for public health.

Purpose of the Study:

  • To uncover unknown causes of cancer using mutational epidemiology.
  • To investigate the impact of mutagenic exposures on a global scale.

Main Methods:

  • Whole-genome sequencing of thousands of cancer and normal tissues.
  • Analysis of data from over 30 countries across five continents.
  • Integration of cancer epidemiology and somatic genomics.

Main Results:

  • Discovery of unsuspected mutagenic exposures affecting millions.
  • Evidence suggesting some carcinogens alter tissue selection forces, not just mutagenesis.
  • Demonstration of altered somatic evolution in normal cells due to exposures and diseases.

Conclusions:

  • Mutational epidemiology is a powerful tool for identifying cancer causes.
  • Environmental and endogenous factors significantly influence cancer development and somatic evolution.
  • Further research into carcinogen mechanisms and tissue microenvironments is warranted.