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The Human Transcriptome Map Reveals Extremes in Gene Density, Intron Length, GC Content, and Repeat Pattern for Domains of Highly and Weakly Expressed Genes

¹ Department of Human Genetics, Academic Medical Center, University of Amsterdam, 1100DE Amsterdam, The Netherlands ² Department of Bioinformatics, Academic Medical Center, University of Amsterdam, 1100DE Amsterdam, The Netherlands ³ Department of Paediatric Oncology/EKZ, Academic Medical Center, University of Amsterdam, 1100DE Amsterdam, The Netherlands ⁴ Swammerdam Institute for Life Sciences, University of Amsterdam, The Netherlands ⁵ Department of Biological Sciences and Center for Computational Biology and Bioinformatics, Columbia University, New York 10027, USA

The chromosomal gene expression profiles established by the Human Transcriptome Map (HTM) revealed a clustering of highly expressed genes in about 30 domains, called ridges. To physically characterize ridges, we constructed a new HTM based on the draft human genome sequence (HTMseq). Expression of 25,003 genes can be analyzed online in a multitude of tissues (http://bioinfo.amc.uva.nl/HTMseq). Ridges are found to be very gene-dense domains with a high GC content, a high SINE repeat density, and a low LINE repeat density. Genes in ridges have significantly shorter introns than genes outside of ridges. The HTMseq also identifies a significant clustering of weakly expressed genes in domains with fully opposite characteristics (antiridges). Both types of domains are open to tissue-specific expression regulation, but the maximal expression levels in ridges are considerably higher than in antiridges. Ridges are therefore an integral part of a higher order structure in the genome related to transcriptional regulation.

[Supplemental material is available online at www.genome.org. The HTMseq application is available online at http://bioinfo.amc.uva.nl/HTMseq].

⁶ Corresponding author.
E-MAIL R.Versteeg{at}AMC.UVA.NL; FAX 0031-20-6918626.

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