Exploiting quantitative trait loci in gene discovery

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Abstract
Developmental biologists prefer to study single gene mu- tations that produce large obvious changes, changes that may be accompanied by lethality or sterility. Such phe- notypes are easy to find in genetic screens and reveal that the gene is required for early, fundamental processes, and thus is important for the organism. Natural variation, however, does not work that way; mutations that lead to sterility or embryonic lethality are quickly weeded out. The alleles selected by nature contribute to survival of the organism, not its detriment. In addition, the varia- tion between two different, naturally occurring popula- tions is not likely to be due to a single gene, but multiple allelic differences. A similar contrast exists when we consider breeding for agricultural purposes versus ge- netic studies in the laboratory. Breeders select for a con- sistent phenotype, and often the traits they select for are subtle, assayed quantitatively in large segregating popu- lations. The traits are usually the result of many gene differences, not single Mendelian mutations. How do we find the genes that distinguish one popu- lation from another, or that distinguish a wild from do- mesticated species? Plants are particularly useful for such studies, as crossing barriers are often geographic, and thus, the experimenter can create F2 progeny that will segregate for the components of the two parental phenotypes. When the F2 individuals do not fall into discrete classes due to segregation at one or two genes, the trait is considered to be quantitatively inherited, and the loci that contribute to the differences between the parents are referred to as quantitative trait loci (QTL).