Discovery Genetics: The History and Future of Spontaneous Mutation Research

Muriel T. Davisson1, David E. Bergstrom1, Laura G. Reinholdt1, Leah Rae Donahue1

1 The Jackson Laboratory, Bar Harbor, Maine
Publication Name:  Current Protocols in Mouse Biology
Unit Number:   
DOI:  10.1002/9780470942390.mo110200
Online Posting Date:  June, 2012
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Historically, spontaneous mutations in mice have served as valuable models of heritable human diseases, contributing substantially to our understanding of both disease mechanisms and basic biological pathways. While advances in molecular technologies have improved our ability to create mouse models of human disease through targeted mutagenesis and transgenesis, spontaneous mutations continue to provide valuable research tools for discovery of novel genes and functions. In addition, the genetic defects caused by spontaneous mutations are molecularly similar to mutations in the human genome and, therefore, often produce phenotypes that more closely resemble those characteristic of human disease than do genetically engineered mutations. Due to the rarity with which spontaneous mutations arise and the animal‐intensive nature of their genetic analysis, large‐scale spontaneous mutation analysis has traditionally been limited to large mammalian genetics institutes. More recently, ENU mutagenesis and new screening methods have increased the rate of mutant strain discovery, and high‐throughput DNA sequencing has enabled rapid identification of the underlying genes and their causative mutations. Here we discuss the continued value of spontaneous mutations for biomedical research. Curr. Protoc. Mouse Biol. 2:103‐118 © 2012 by John Wiley & Sons, Inc.

Keywords: spontaneous mutations; mouse models; forward genetics; biomedical research

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Table of Contents

  • Introduction
  • Advantages of Spontaneous Mutation Analysis
  • Challenges of Spontaneous Mutation Analysis
  • History of Spontaneous Mutation Discovery and Development
  • Protocols for Genetic Analysis: Then and Now
  • Summary and Conclusions
  • Acknowledgments
  • Literature Cited
  • Tables
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