Recessive Lethal Mutations in Diploids Can Be Identified by Inbreeding and Maintained in Heterozygotes

In diploid organisms, phenotypes resulting from recessive mutations can be observed only in individuals homozygous for the mutant alleles. Since mutagenesis in a diploid organism typically changes only one allele of a gene, yielding heterozygous mutants, genetic screens must include inbreeding steps to generate progeny that are homozygous for the mutant alleles. The geneticist H. Muller developed a general and efficient procedure for carrying out such inbreeding experiments in the fruit fly Drosophila. Recessive lethal mutations in Drosophila and other diploid organisms can be maintained in heterozygous individuals and their phenotypic consequences analyzed in homozygotes.

The Muller approach was used to great effect by C. Nusslein-Volhard and E. Wieschaus, who systematically screened for recessive lethal mutations affecting embryogenesis in Drosophila. Dead homozygous embryos carrying recessive lethal mutations identified by this screen were examined under the microscope for specific morphological defects in the embryos. Current understanding of the molecular mechanisms underlying development of multicellular organisms is based, in large part, on the detailed picture of embryonic development revealed by characterization of these Drosophila mutants. We will discuss some of the fundamental discoveries based on these genetic studies in Chapter 15.

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