Forward genetics
Encyclopedia
Forward genetics is an approach that encompasses several means of identifying the gene or set of genes that are responsible for a particular phenotype within an organism. Initially, this entailed the generation of random mutations in an organism, often through radiation or insertional mutagenesis
(ex. Sleeping Beauty)
, and then through a series of breeding of subsequent generations, isolating individuals with an aberrant phenotype. Today there are many different means of following the general path of altering the genotype to observe the phenotype, several of which within the genomic era can be 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.
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.
Insertional mutagenesis
Insertional mutagenesis is mutagenesis of DNA by the insertion of one or more bases.Insertional mutations can occur naturally, mediated by virus or transposon, or can be artificially created for research purposes in the lab.- Signature tagged mutagenesis :...
(ex. Sleeping Beauty)
Sleeping Beauty transposon system
The Sleeping Beauty transposon system is a synthetic DNA transposon that was constructed to introduce precisely defined DNA sequences into the chromosomes of vertebrate animals for the purposes of introducing new traits and to discover new genes and their functions.-Mechanism of Action:The Sleeping...
, and then through a series of breeding of subsequent generations, isolating individuals with an aberrant phenotype. Today there are many different means of following the general path of altering the genotype to observe the phenotype, several of which within the genomic era can be useful in the study of functional genomics
Functional genomics
Functional genomics is a field of molecular biology that attempts to make use of the vast wealth of data produced by genomic projects to describe gene functions and interactions...
. Forward genetics can be thought of as a counter to reverse genetics
Reverse genetics
Reverse genetics is an approach to discovering the function of a gene by analyzing the phenotypic effects of specific gene sequences obtained by DNA sequencing. This investigative process proceeds in the opposite direction of so-called forward genetic screens of classical genetics...
, which seeks to alter genes in order to illuminate their multiple phenotypes.
Classical forward genetics
By the classical geneticsClassical genetics
Classical genetics consists of the technique and methodologies of genetics that predate the advent of molecular biology. A key discovery of classical genetics in eukaryotes was genetic linkage...
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.