International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 224 - MUTAGENESIS OF CENTRAL MOUSE CHROMOSOME 4: FUNCTIONAL ANALYSIS OF THE TYRP1 (BROWN) DELETION COMPLEX

Dr Anita Holdsworth
Baylor College of Medicine
Dept of Molecular & Human Genetics
One Baylor Plaza
Houston
77030
USA

Co-Authors: Brown E, Justice MJ
Institutions: Dept. of Molecular & Human Genetics, Baylor College of Medicine

High resolution molecular and functional analysis of the tyrosine related protein 1 (Tyrp1) or brown locus on mouse Chr 4 is possible because of overlapping deletions spanning a 20 Mb interval.  Several functional units have already been identified within this deletion complex, including depilated (dep), brown associated fitness (baf), and three lethal complementation groups.   Moreover, genes implicated in developmental and/or neurological processes, and others involved in inflammation, wound healing, or immune responses, have been mapped to this region. In collaboration with the MRC-Harwell Mouse Genetics Unit, and MRC-Edinburgh Human Genetics Unit, we are building a sequence-ready physical contig of the entire deletion region (see abstract Smyth et al.).

To carry out functional analysis of the interval, ENU mutagenesis is being used to isolate mutations that represent single gene functional units.  Pilot experiments have indicated a new mutation in approximately every 25 gametes screened, reflecting the relative gene rich content of the brown deletion region.  Our goal is to saturate the region with mutations to generate multiple allelic series, and then correlate the mutations with candidate genes.  Information on functional redundancy will be ascertained from genes that do not mutate to a discernable phenotype.  This approach should generate new models of human diseases encoded by the conserved region on human Chr 9.


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