Forward genetics encompasses several means of identifying the genotype that is responsible for a phenotype. Initially, this was done by generating random mutations in an organism, often with radiation or insertional mutagenesis (e.g. through the Sleeping Beauty system), and after subsequent breeding, isolating individuals with an aberrant phenotype. Today there are many means of altering the genotype to observe the phenotype, several of which are useful in the study of functional genomics. Forward genetics can be thought of as a counter to reverse genetics, which seeks to alter genes in order to illuminate their multiple phenotypes. Traditionally, forward genetics involves the use of mutagens (e.g. EMS) and the underlying phenotype would be observed by genetic mapping. Reverse genetics however, due to the advent of advances in sequencing is employed to seek out what sequences underlies the phenotype.
Classical forward genetics
By the classical genetics approach, a researcher would then locate (map) the gene on its chromosome by crossbreeding with individuals that carry other unusual traits and collecting statistics on how frequently the two traits are inherited together. Classical geneticists would have used phenotypic traits to map the new mutant alleles. Eventually the hope is that such screens would reach a large enough scale that most or all newly generated mutations would represent a second hit of a locus, essentially saturating the genome with mutations. This type of saturation mutagenesis within classical experiments was used to define sets of genes that were a bare minimum for the appearance of specific phenotypes. However, such initial screens were either incomplete as they were missing redundant loci and epigenetic effects, and such screens were difficult to undertake for certain phenotypes that lack directly measurable phenotypes. Additionally a classical genetics approach takes significantly longer.
- Greg Gibson and Spencer V. Muse. 2009. A Primer of Genome Science, Third Edition. Sinauer Press.
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