International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany

Plenary Presentations * Oral Presentations *
Poster Presentations: Behavioural Genetics and Genomics * Development and Stem Cells * Functional Genome Analysis * Mouse Models of Human Disease * Mouse System Biology Bioinformatics * Multigenic and Multifactorial Trait Analysis * Nutrition and Metabolic Disease * Phenotyping Methods Imaging * The Genetics and Genomics of Infectious Disease *
Verne Chapman Memorial Lecture * Table of Contents * Sponsor/Exhibitor List * Awards * Photographs

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POSTER 59 - DIRECTED MUTAGENESIS OF THE BROWN LOCUS ON CHROMOSOME 4 AND A HIGH THROUGHPUT SEQUENCE BASED SCREEN TO IDENTIFY MUTATIONS

Smyth I
MRC Human Genetics Unit, Edinburgh

Co-Authors: 2) Holdsworth A, 1) Edgar R, 1) White S, 1) Taylor M, 1) Gautier P, 2) Justice M, 1) Jackson I
Institutions: 1) MRC Human Genetics Unit, Edinburgh, 2) Baylor College of Medicine, Houston TX

The brown (Tyrp1) locus on mouse chromosome 4 is one of the best studied regions of the mouse genome. Over the last 50 years a panel of 27 independent deletions, generated from a variety of mutagenic protocols, have been characterised within this region. We have utilised this resource and finished sequence from a BAC contig across this 22Mb interval to define deletion breakpoints and to identify candidate genes for several mouse phenotypes known to map to this region. In particular we present analysis of candidate genes for two mutants; depilated (dep), a spontaneous mutation affecting the coat and brown associated fitness (baf), a semi-viable mutant. Using the deletions as the basis for an ENU mutagenesis screen we have identified 24 recessive mutant mouse lines whose phenotypes range from lethality to defects of behaviour and development. In collaboration with the Wellcome Trust Sanger Institute we intend to utilise a high throughput approach to identify the mutations underlying these phenotypes. The genomic region encompassed by the brown deletions is relatively gene poor and this, in combination with the large panel of mutants and finished and annotated genomic sequence, means that it will be economically feasible to sequence all of the exons in all of the mutant animals.