Mind the phenotype gap

Abstract

This meeting brought together over 100 scientists with a common interest in using genetic approaches in mice to study human biology. One of the strengths of the meeting was the diversity of subject areas covered. Presentations were given on mouse models of both simple and complex human disorders including developmental abnormalities, inflammatory diseases, cancer, and CNS diseases. Mixed in were a number of talks describing the latest techniques currently used to study gene function in the mouse, such as N-ethyl-Nnitrosourea (ENU) mutagenesis screens, DNA microarrays, and gene targeting. It was also readily apparent that Celera’s recent completion of the mouse genome sequence, as well as new programs to analyze this information, have made a significant impact on the speed with which investigators can localize and identify candidate genes that contribute to a particular phenotype. The first two days featured a variety of talks given on models of human disorders and genome analysis technology. The final session was largely focused on ENU mutagenesis screens. Martin Hrabe de Angelis (GSF Research Center for Environment and Health, Munich, Germany) began the session by describing his strategies for solving the ‘phenotype gap’. This term refers to a major problem in mouse genetics, basically that mutations have only been described for only a small number of genes. In his talk, he outlined the Munich-ENU screen, designed to identify both dominant and recessive mutations affecting a variety of organ systems. Over 300 mutant lines have now been generated from this work. A description of the genetically confirmed mutants from this ongoing project is available at http://www.gsf.de/ieg. Shigeharu Wakana (RIKEN Genomics Sciences Center, Yokohama, Japan) gave an overview of the RIKEN mutagenesis project. This effort is focused on identifying late-onset phenotypes such as tumorigenesis, diabetes, hypertension, and neurodegeneration. He also discussed Mind the phenotype gap