Insertional Mutagenesis in Zebrafish

Abstract

Classical forward genetics identifies genes based upon the phenotype that results when the gene is mutated; the gene itself can then be molecularly cloned. This is in contrast to reverse genetics, in which the consequences of the absence of gene products are determined either through the use of inhibitors of the gene products, the expression of dominant negative alleles, or, in the case of mice, the use of homologous recombination in embryonic stem (ES) cells to create a null allele of the gene. The primary distinction between the reverse genetic approaches and the forward genetic approach is that in the former, the gene products must be identified prior to the assessment of their role in a biological process, while in the latter it is their essential role in that process which identifies them. If one’s interest is to define the role of a specific protein, a specific signaling pathway, or a gene whose human homologue is implicated in a disease, then the reverse genetics approaches are ideal. However, if one’s primary interest is, for example, a developmental process, the most straight forward way to identify the genes essential or that process is to perform a forward genetic screen.