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

D6 Comparative Sequence Analysis of 1.5 Mb from Mouse Chromosome X and Its Corresponding Regions in Human Xq28

Platzer, M.1, Reichwald, K.1, Galgoczy, P.1, Goremykin. V.1, Geist, S.1, Zhao, W.2, Herman, G.E.2, Rosenthal, A.1,3. 1Institute of Molecular Biotechnology, Jena, Germany; 2Children's Hospital Research Foundation and The Ohio State University, Columbus, Ohio, US; 3Friedrich-Schiller University, Jena, Germany

The distal end of the long arm of the human X-chromosome, Xq28, is distinguished by a region of high gene density. In addition, many disease genes have been mapped to this region. At present, more than 4 Mb of Xq28 have been sequenced, most of it by the Genome Sequencing Centre in Jena. The available sequence data reveals remarkable heterogeneity with respect to gene density, repeat content and base composition.

In order to investigate the organization and evolution of Xq28 we are currently sequencing syntenic regions of the mouse X-chromosome, band A. This approach allows the identification of conserved regions in mouse and man which can then be investigated for their coding or regulatory potential. Starting from mouse markers Mtm1, Gabre, Aldgh, Mecp2, G6pdx we have constructed sequence-ready BAC/PAC contigs spanning more than 2 Mb. By sequencing of about 1.5 Mb we identified more than 30 genes including Xap80, Mtm1, Mtmr1, Xap89, Gabre, Aldgh, Idh3g, L1cam, Avpr2, Renbp, Hcfc1, Mecp2, Rsvp. Moreover, in intergenic regions there are several sequence elements, which are >200 bp and exhibit an identity >80% and therefore are likely to be involved in regulatory processes.

We present results of the comparative analysis of two human and murine sequence contigs at the MTM1/Mtm1 and MECP2/Mecp2 loci. At the MTM1/Mtm1 locus we studied in detail an ancient gene duplication, which occurred long before divergence of primate and rodent lineages, 340 vs 75 Myr B.P. At the MECP2/Mecp2 locus we observed remarkable differences in the G+C content: Whereas the human locus is comprised of two H3 isochores, in the mouse transitions to H2 and H1 isochores occurred. Furthermore, by comparison of selected coding and noncoding regions we observed local differences in rates of divergence. We present a detailed inter- and intraspecific comparison of gene content, G+C composition and repeat distribution.

This work contributes to the systematic comparative analysis of mouse X chromosome within 4 cM between Ids and Dmd (, please see also abstracts by Galgoczy, Bates and Straw).


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