Hi, in this video, we're going to be talking about genetic screens. Genetic screens are a significant technique that scientists use to evaluate the functions of thousands of genes at once. We have mainly been focusing on identifying the function of one gene, which is beneficial if you already have an idea of which genes to target. For example, you knock out one gene that you think is involved in cell growth, and you discover that it is indeed involved. That's great, but if you have the entire genome sequence and you have no idea about any of the genes within it, then targeting one specific gene or one gene at a time becomes impossible because there are way too many genes. Genetic screens are important because you don't need to have prior knowledge of the genome's layout, the gene locations, or their probable functions. It allows you to say, "We have no idea, so let's test all the genes," or at least most of them. Genetic screens are incredibly powerful, but they require you to take in the entire genome at once and then narrow down, step by step, to genes with a specific function. Typically, in a genetic screen, you consider what function you want to examine. For instance, if you're interested in cell growth, you would conduct a genetic screen looking for organisms that have impairments in cell growth.
The process involves exposing the entire organism to a mutagen, which is known to cause mutations, thus producing random gene alterations across the genome. Some of these mutations might lead to the death of organisms, but most will result in odd effects. These mutations could alter attributes like shape, size, growth, metabolism, or color—any phenotype. However, since your interest is in one specific phenotype, such as cell growth, you expose the organism to the mutagen, inducing numerous mutations and a variety of phenotypes, then select the organisms that exhibit defects in cell growth or size. Once you have identified a group of organisms exhibiting the phenotype of interest, additional testing can refine and identify the specific gene responsible for that phenotype.
Genetic screens are typically effective for non-lethal mutations, as they allow further testing. However, if you wish to study a gene so essential that mutation could be fatal, a special approach called a conditional mutant is used. Conditional mutants express mutations only under specific conditions, such as temperature changes, enabling the study of potentially lethal genetic alterations while keeping the organism alive long enough for study.
An example of a genetic screen might involve bacteria, which could undergo mutation by a mutagen affecting all their DNA and resulting in varied phenotypes. You would then select mutants that show changes in cell size for further analysis. To further identify and understand the gene's function, you could employ tests such as a complementation test or an epistasis analysis. In a complementation test, you determine whether mutations causing similar phenotypes lie within the same gene, while epistasis analysis helps elucidate the ordering within a signaling pathway affected by mutations. These methods are crucial in combining observations from genetic screens with detailed genetic analysis to ascertain a gene’s function.
