Abstract
Careful manual annotation of the human reference sequence provides a solid basis for the identification of disease-associated genes. Toward this end, we focused on a medically relevant 2.6-Mb region of the human chromosome Xp11.4 between markers DXS9851 and DXS9751 and identified 16 transcription units according to the Vertebrate Genome Annotation (Vega) rules. In order to validate these annotations, we performed a comprehensive RT-PCR expression analysis and a human-mouse comparison. This revealed, despite the high overall genomic conservation of the region, remarkable differences of the gene content between human and mouse. Whereas 12 of 16 annotations were confirmed by RT-PCR in human tissues, for only seven genes mouse orthologs could be identified and found to be expressed. This indicates that a comprehensive and experimentally supported annotation effort of the human genome simultaneously highlights regions with striking differences in gene organization to other species and may indicate evolutionary events specific to the human lineage demanding further functional analyses.
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Acknowledgments
The authors thank Elke Meier, Petra Eißmann, and Kathleen Seitz for excellent technical help in DNA sequencing and RT-PCR. They are grateful to Michael B. Gorin and associates at the University of Pittsburgh for offering three BACs, to the Whitehead Institute for Biomedical Research/MIT and the Washington University Genome Sequencing Center for providing working draft data of four BACs, and the Sanger Centre Hinxton, UK, for the finished sequence of one BAC. This work was supported by the German Ministry for Research and Education (BMBF, German Human Genome Project grant 01KW9916 to MP and 01KW9974 to AM) and by a grant from the European community (EC, QLG2-CT-1999-00791) to AM.
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Wen, G., Ramser, J., Taudien, S. et al. Validation of mRNA/EST-based gene predictions in human Xp11.4 revealed differences to the organization of the orthologous mouse locus. Mamm Genome 16, 934–941 (2005). https://doi.org/10.1007/s00335-005-0090-3
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DOI: https://doi.org/10.1007/s00335-005-0090-3