4.4 Review

The dawn of active genetics

Journal

BIOESSAYS
Volume 38, Issue 1, Pages 50-63

Publisher

WILEY
DOI: 10.1002/bies.201500102

Keywords

active genetics; copy cat element; Drosophila; ERACR; gene drive; MCR; mutagenic chain reaction

Funding

  1. NIAID NIH HHS [R56 AI070654] Funding Source: Medline
  2. NINDS NIH HHS [R56 NS029870] Funding Source: Medline
  3. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R56AI070654] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R56NS029870] Funding Source: NIH RePORTER

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On December 18, 2014, a yellow female fly quietly emerged from her pupal case. What made her unique was that she had only one parent carrying a mutant allele of this classic recessive locus. Then, one generation later, after mating with a wild-type male, all her offspring displayed the same recessive yellow phenotype. Further analysis of other such yellow females revealed that the construct causing the mutation was converting the opposing chromosome with 95% efficiency. These simple results, seen also in mosquitoes and yeast, open the door to a new era of genetics wherein the laws of traditional Mendelian inheritance can be bypassed for a broad variety of purposes. Here, we consider the implications of this fundamentally new form of active genetics, its applications for gene drives, reversal and amplification strategies, its potential for contributing to cell and gene therapy strategies, and ethical/biosafety considerations associated with such active genetic elements.

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