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The mutagenic chain reaction: A method for converting heterozygous to homozygous mutations

Science  24 Apr 2015:
Vol. 348, Issue 6233, pp. 442-444
DOI: 10.1126/science.aaa5945

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Generating homozygous mutations

Loss-of-function mutations may only produce a mutant phenotype when both copies of the gene are mutated. Gantz and Bier developed a method they call mutagenic chain reaction (MCR) that autocatalytically produces homozygous mutations. MCR uses the initial mutated allele to cause a mutation in the allele on the opposing chromosome and thus the homozygosity of the trait. MCR technology could have broad applications in diverse organisms.

Science, this issue p. 442

Abstract

An organism with a single recessive loss-of-function allele will typically have a wild-type phenotype, whereas individuals homozygous for two copies of the allele will display a mutant phenotype. We have developed a method called the mutagenic chain reaction (MCR), which is based on the CRISPR/Cas9 genome-editing system for generating autocatalytic mutations, to produce homozygous loss-of-function mutations. In Drosophila, we found that MCR mutations efficiently spread from their chromosome of origin to the homologous chromosome, thereby converting heterozygous mutations to homozygosity in the vast majority of somatic and germline cells. MCR technology should have broad applications in diverse organisms.

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