QTL analysis and genomewide mutagenesis in mice: Complementary genetic approaches to the dissection of complex traits - Commentary

Quantitative genetics and quantitative trait locus (QTL) mapping have under gone a revolution in the last decade. Progress in the next decade promises to be at least as rapid, and strategies for fine-mapping QTLs and identifyi ng underlying genes will be radically revised. In this Commentary we addres s several key issues: first, we revisit a perennial challenge-how to identi fy individual genes and allelic variants underlying QTLs. We compare curren t practice and procedures in QTL analysis with novel methods and resources that are just now being introduced. We argue that there is no one standard of proof for showing QTL = gene; rather, evidence from several. sources mus t be carefully assembled until there is only one reasonable conclusion. Sec ond, we compare QTL analysis with whole-genome mutagenesis in Mice and poin t out some of the strengths and weakness of both of these phenotype-driven methods. Finally, we explore the advantages and disadvantages of naturally occurring vs mutagen-induced polymorphisms. We argue that these two complem entary-genetic methods have much to offer in efforts to highlight genes and pathways most likely to influence the susceptibility and progression of co mmon diseases in human populations.