International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


Oral Presentation

Sunday 17 November

16:30 - 16:45 HRS

SEQUENCING AND TARGETED ANALYSIS OF MOUSE CHROMOSOMES 2, 4, 11 & X

S.G. Gregory
The Wellcome Trust Sanger Institute

Co-Authors: Barrett I, Sims S, Williams S, Plumb R, Mathews L, McLay K, Grafham D, Hunt A, Jones M, Wilming L, Ashurst J, Beck S, Rogers J
Institutions: 1) Wellcome Trust Genome Campus

The recent generation of a physical map and whole genome shotgun sequence of the mouse genome has already greatly contributed to the definition of the gene set of the  mouse, and comparative analyses between human and mouse genomes. The production of finished sequence to the recognised 'gold standard' as generated for the HGP, is of primary importance for the complete elucidation of coding and non-coding features within the sequence. The Sanger Institute (in conjunction with MRC Harwell, UK and BCM Houston, US) is constructing contiguous physical map and finished sequence coverage of mouse chromosomes 2, 4, 11 and X, 20% of the mouse genome. Here we describe the rapid progress of these chromosome projects, including the closure of gaps in the physical map by utilizing syntenic human sequence as well as the use of whole genome shotgun sequence for directed finishing. The mouse X chromosome poses particular challenges for the generation of contiguous sequence. The presence of duplications and a high repeat density have resulted in regions that are not well resolved in the whole genome sequence assembly. This will be illustrated by a detailedcomparative analysis of a 15Mb region of mouse and human X chromosomes extending from DXS1510 to DXS8088 in human Xq22-Xq23, and from DXMIT117 to DXMIT155 in mouse. This region contains genes associated with human disorders, such as COL4A5 (Alports syndrome) and PLP (Pelizaeus-merzbacher disease). This region in the human also contains a number of genes with a high degree of similarity, the ortholog of which may be identified by genomic sequence from the mouse.


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