Forward Genetic approach

"forward genetics," is dependent on knowing something about the pathophysiology of the disorder. This is a "candidate gene" approach in which one attempts to make an educated guess about which genes might be involved in a trait or disorder and to employ molecular genetics to prove that the gene actually is responsible. An efficient "candidate gene" approach is not yet generally possible in the study of mental disorders because we are so early in our understanding of pathophysiology. Moreover, the percentage of the genes expressed in brain that have been identified is still so small that success with this is approach is still several years away. One type of candidate gene strategy (described by Malhotra and Goldman in this issue) is to try to attach phenotypes to allelic variants in genes known to encode important proteins in the brain (e.g., dopmaine or serotonin receptors). This forward genetics approach is used a great deal in mouse models where the gene of interest is actually inserted into the mouse genome (resulting in transgenic mice) or deleted from the mouse genome by homologous recombination (yielding so-called gene knockout mice). Critical to the analysis of what a gene does in mouse experiments is the use of inbred strains, which provide a uniform genetic background against- which to observe the phenotype produced by the allele of interest (including a null allele in a knockout). Because of the existence of modifier genes for literally all traits, alleles may have strikingly different effects within different mouse strains. Since humans are far from inbred, finding the effect of a given allele is difficult indeed, unless the effect of the allele is very large.

출처 : http://www.nimh.nih.gov/about/complexgenetics.cfm