International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

C4 Comparative Mouse Genome Sequencing for Systematic Studies of Mammalian Gene Function

Steve Brown. MRC Mammalian Genetics Unit and UK Mouse Genome Centre, Harwell, OX11 ORD, UK

A number of studies suggest that there appear to be considerable advantages to the acquisition and comparison of both human and mouse genome sequence in order to aid comprehensive gene identification and annotation, as well as the characterisation of putative regulatory elements. Work at the UK Mouse Genome Centre with colleagues at the MRC HGMP Resource Centre, UK, Ohio State, US and Jena, Germany, has focussed on the comparative sequencing of the mouse X chromosome and in particular a 500kb region containing the Bpa and Str mutations. Comparisons of mouse and human sequence across this region have allowed the identification and annotation of a number of novel genes, as well as aiding in the determination of the detailed gene structure of a number of known genes. The determination of the structure of the Nsdhl gene in this region from the ongoing sequencing efforts was one factor in the identification of this novel steroid dehydrogenase as the locus underlying the Bpa and Str mutations (Liu et al., 1999, Nature Genetics 22: 182-187). It is clear that the acquisition of the mouse genome sequence will be a vital element for future mammalian gene function studies, and in particular phenotype-driven ENU mutagenesis programmes. Comparative mouse and human genome sequence will be an important tool for exploiting the rapidly growing mouse mutant resource and moving from phenotype to gene. The acquisition of mouse genome sequence is likely to occur in two complementary ways that might be described as genome-wide and regional/functional. A working draft of the mouse genome will be delivered on a genome-wide basis. Other sequencing programmes will focus on the production of finished sequence for specific regions sooner rather than later. A UK mouse sequencing programme funded by the Medical Research Council for three years will adopt a regional/functional approach targeted to four regions on chromosomes 4, 13, 2 and X. For each of these four regions there are already significant research efforts ongoing focused on systematic determination of gene function through mutagenesis and other studies. The UK effort will focus on the delivery of finished, contiguous sequence. It is expected that the availability of high-quality sequence will significantly leverage research efforts in gene function studies in these four chromosome regions.


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