Patrick J. Krysan 1 ,a , Jeffery C. Young 1 , 2 ,a , and Michael R. Sussman a a Biotechnology Center, University of Wisconsin, 425 Henry Mall, Madison, Wisconsin 53706 Correspondence to: Michael R. Sussman, firstname.lastname@example.org (E-mail), 608-262-6748 (fax) INTRODUCTION TOP INTRODUCTION PROPOSED NOMENCLATURE SATURATING THE GENOME WITH... SCREENING LARGE POPULATIONS OF... THE IMPORTANCE OF TESTING... CHARACTERIZATION OF PHENOTYPES CONFIRMING CORRELATIONS BETWEEN... ESTABLISHMENT OF A NATIONAL... BEYOND PCR SCREENING CONCLUSION REFERENCES Forward genetics begins with a mutant phenotype and asks the question "What is the genotype?" that is, what is the sequence of the mutant gene causing the altered phenotype? Reverse genetics begins with a mutant gene sequence and asks the question "What is the resulting change in phenotype?" These two approaches are fundamentally different, and whereas forward genetics has been in operation for more than a century, the recent avalanche of complete genome sequences has only now created the opportunity for pursuing reverse genetics in an exhaustive and complete manner. Gene knockouts, or null mutations, are important because they provide a direct route to determining the function of a gene product in situ. Most other approaches to gene function are correlative and do not necessarily prove
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