The elucidation of the functional content of the genome of a model organism, such as the mouse, involves identification of genes and evolutionarily conserved non-transcribed sequences through genome sequencing, analysis of gene expression and analysis of normal and mutant phenotypes. This grant application is being prepared at an exciting time for mammalian biology, when each one of these efforts is being undertaken on a large scale - whole genome level. In this project we propose to initiate the integration of these functional genomics data, using a 100 Mb chromosomal region of the mouse genome as a model.
Our aims are to (1) identify, characterize and clone a set of novel embryo-lethal mutations within the 30cM/60 Mb region covered by the Rw inversion (2) perform functional analysis of the cluster of GABAA receptor subunit genes by generation of Embryonic Stem (ES) cells with chromosomal deletions and phenotypic analysis of mice carrying these deletions and (3) assemble a gene index and perform comparative sequence analysis of genes shown to be involved in developmental processes (based on mutant analysis and/or available expression data). The minimal set of genes necessary for embryonic survival is a key question in developmental biology. In this proposal we use a defined chromosomal region, representing 2 percent of the mouse genome, and available genetic, genomic and bioinformatics resources to systematically search for and catalog these genes and their mutant phenotypes.
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