I. Use computer search to identify homologous genes or peptide motifs whose function is known. A wide variety of functional motifs is known. Examples include LRR's and Zinc finger proteins. This approach provide clues to function of the protein, but not all motifs and homologues do the same thing. Use chemical or UV Mutagenesis to induce deletion mutants, then PCR to detect deletion mutants in particular known sequences with unknown function.
Homologous recombination exchanges the native mouse gene for the mutant gene.
Several offspring that were chromosomally female developed male sex organs. Both methods use linkage mapping to identify the genomic region containing loci that influence a trait of interest. However, QTL mapping seeks the loci underlying a quantitative, i.e. continuously varying trait, where as positional cloning is often targetting discrete phenotypes. Both may use successive rounds of mapping to narrow the region of interest. It is generally the case that several to many loci control the quantitative trait, whereas one or a few loci control the discrete trait, though this is not always true.