| The Virtues of Knockouts |
Gene prediction programs have been valuable in the preliminary identification of genes; however, they have limitations. Unless the gene of interest is homologous to a gene of known function, the function is generally still not known. A biological approach to determining the function of a gene is to create a mutation and then observe the effect of the mutation on the organism. This is called a knockout study. While it is not ethical to create knockout mutants in humans, many such mutants are already known, especially those that cause disease. One advantage of having a genome sequence is that it greatly facilitates the identification of genes in which mutations lead to a particular disease.
The mouse, where one can make and characterize knockout mutants, is an excellent model system for studying genetic diseases of humans; its genome is remarkably similar to a human's. Nearly all human genes have homologs in mice, and large regions of the chromosomes are very well conserved between the two species. In fact, human chromosomes can be (figuratively) cut into about 150 pieces, mixed and matched, and then reassembled into the 21 chromosomes of a mouse. Thus, it is possible to create mutants in mice to determine the probable function of the same genes in humans. Genetic stocks of mutant mice have been developed and maintained since the 1940s.
One goal of the mouse genome project is to make and characterize mutations in order to determine the function of every mouse gene. After a particular gene mutation has been linked to a particular disorder, the normal function of the gene may be determined. An example of this approach is the mutated gene that resulted in cleft palates in mice. The researchers found that the gene's normal function is to close the embryo's palate. An understanding of the genetics behind cleft palate in mice may one day be used to help prevent this common birth defect in humans.