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Mutation, Gene Flow, and Genetic Drift01:09

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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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Chromosomal Alterations Are Large-Scale Mutations
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A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
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Generation of Comprehensive Thoracic Oncology Database - Tool for Translational Research
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Pig-a gene mutation database.

Jennifer M Shemansky1, Lea Patrice McDaniel1, Christopher Klimas2

  • 1Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, Arkansas.

Environmental and Molecular Mutagenesis
|May 16, 2019
PubMed
Summary
This summary is machine-generated.

The Pig-a gene mutation assay detects genetic damage by measuring lost cell surface proteins. A new public database aids regulatory acceptance and comparative analysis of this important genotoxicity test.

Keywords:
assay regulatory acceptancedetailed review paperglycosylphosphatidylinositol (GPI)mouse and ratphosphatidylinositol glycan, class A generetrospective performance analysis

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Area of Science:

  • Toxicology
  • Genetics
  • Biochemistry

Background:

  • Mutations in the X-linked phosphatidylinositol glycan, class A (Pig-a) gene cause loss of glycosylphosphatidylinositol (GPI) anchors and associated proteins on cell surfaces.
  • This phenomenon affects erythrocytes and other mammalian cells, serving as a biomarker for genetic damage.

Purpose of the Study:

  • To establish a public database for Pig-a gene mutation assay data to support regulatory acceptance.
  • To facilitate the Retrospective Performance Analysis and Detailed Review Paper for OECD Test Guideline acceptance.
  • To enable comparative analysis of Pig-a assay data with other toxicological assays.

Main Methods:

  • The Pig-a gene mutation assay quantifies in vivo gene mutations.
  • Utilizes immunofluorescent labeling and flow cytometry to detect the loss of GPI-anchored proteins on peripheral blood erythrocytes.
  • A searchable public database was created and is hosted online.

Main Results:

  • A public database containing Pig-a gene mutation assay data from rats and mice has been established.
  • The database is searchable and available online, facilitating data access.
  • The database is intended to expand to include data from other species, including humans.

Conclusions:

  • The Pig-a gene mutation assay database is crucial for regulatory acceptance of the assay.
  • The database will serve as a valuable resource for researchers studying genotoxicity and comparative toxicology.
  • Future expansion to include human data will enhance its utility for risk assessment.