Positional cloning

A genetic screen or mutagenesis screen is an experimental technique used to identify and select for individuals who possess a phenotype of interest in a mutagenized population. Hence a genetic screen is a type of phenotypic screen. Genetic screens can provide important information on gene function as well as the molecular events that underlie a biological process or pathway. While genome projects have identified an extensive inventory of genes in many different organisms, genetic screens can provide valuable insight as to how those genes function.

Forward genetics (or a forward genetic screen) is an approach used to identify genes (or set of genes) responsible for a particular phenotype of an organism. Reverse genetics (or a reverse genetic screen), on the other hand, analyzes the phenotype of an organism following the disruption of a known gene. In short, forward genetics starts with a phenotype and moves towards identifying the gene(s) responsible, where as reverse genetics starts with a known gene and assays the effect of its disruption by analyzing the resultant phenotypes. Both forward and reverse genetic screens aim to determine gene function.

Successful forward genetic screens often have two key components. The first is a defined genetic background of the organism being used and the second is a simple yet constant experimental procedure to identify mutants of interest. Defined genetic backgrounds allow researchers to identify and locate affected genes in mutant individuals with greater efficiency. A simplified screening method is beneficial because it allows for a larger number of individuals to be screened, thereby increasing the probability of generating and identifying mutants of interest.

Since natural allelic mutations are rare, prior to screening geneticists often mutagenize a population of individuals by exposing them to a known mutagen, such as a chemical or radiation, thereby generating a much higher frequency of chromosomal mutations. In some organisms mutagens can be useful for performing saturation screens. Saturation screens are used to uncover all genes involved in a particular phenotype of an organism or species. The screen is carried out by mapping mutants of a biological process until no new genes/gene mutations can be found. Christiane Nüsslein-Volhard and Eric Wieschaus were the first individuals to perform this type of screening procedure.

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