This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: 1934904v1 14/5/852    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dermitzakis, E. T. Articles by Antonarakis, S. E. Search for Related Content PubMed PubMed Citation Articles by Dermitzakis, E. T. Articles by Antonarakis, S. E. Social Bookmarking                   What's this?

Letter

Comparison of Human Chromosome 21 Conserved Nongenic Sequences (CNGs) With the Mouse and Dog Genomes Shows That Their Selective Constraint Is Independent of Their Genic Environment

¹ Division of Medical Genetics, University of Geneva Medical School, CH-1211 Geneva, Switzerland ² The Institute for Genomic Research (TIGR), Rockville, Maryland 20850, USA ³ Department of Computer Sciences and Engineering, Pennsylvania State University, Pennsylvania 16802, USA ⁴ European Bioinformatics Institute, Hinxton CB10 1SD, UK

The analysis of conservation between the human and mouse genomes resulted in the identification of a large number of conserved nongenic sequences (CNGs). The functional significance of this nongenic conservation remains unknown, however. The availability of the sequence of a third mammalian genome, the dog, allows for a large-scale analysis of evolutionary attributes of CNGs in mammals. We have aligned 1638 previously identified CNGs and 976 conserved exons (CODs) from human chromosome 21 (Hsa21) with their orthologous sequences in mouse and dog. Attributes of selective constraint, such as sequence conservation, clustering, and direction of substitutions were compared between CNGs and CODs, showing a clear distinction between the two classes. We subsequently performed a chromosome-wide analysis of CNGs by correlating selective constraint metrics with their position on the chromosome and relative to their distance from genes. We found that CNGs appear to be randomly arranged in intergenic regions, with no bias to be closer or farther from genes. Moreover, conservation and clustering of substitutions of CNGs appear to be completely independent of their distance from genes. These results suggest that the majority of CNGs are not typical of previously described regulatory elements in terms of their location. We propose models for a global role of CNGs in genome function and regulation, through long-distance cis or trans chromosomal interactions.

⁵ Corresponding authors.
E-MAIL Emmanouil.Dermitzakis{at}medecine.unige.ch; FAX 0041-22-379-5706.

E-MAIL Stylianos.Antonarakis{at}medecine.unige.ch; FAX 0041-22-379-5706.

[Supplemental material is available online at www.genome.org.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				Y. Shima, M. Zubair, T. Komatsu, S. Oka, C. Yokoyama, T. Tachibana, T. A. Hjalt, J. Drouin, and K.-i. Morohashi Pituitary Homeobox 2 Regulates Adrenal4 Binding Protein/Steroidogenic Factor-1 Gene Transcription in the Pituitary Gonadotrope through Interaction with the Intronic Enhancer Mol. Endocrinol., July 1, 2008; 22(7): 1633 - 1646. [Abstract] [Full Text] [PDF]

				N. Sabherwal, F. Bangs, R. Roth, B. Weiss, K. Jantz, E. Tiecke, G. K. Hinkel, C. Spaich, B. P. Hauffa, H. van der Kamp, et al. Long-range conserved non-coding SHOX sequences regulate expression in developing chicken limb and are associated with short stature phenotypes in human patients Hum. Mol. Genet., January 15, 2007; 16(2): 210 - 222. [Abstract] [Full Text] [PDF]

				J. de Meaux, A. Pop, and T. Mitchell-Olds Cis-regulatory Evolution of Chalcone-Synthase Expression in the Genus Arabidopsis Genetics, December 1, 2006; 174(4): 2181 - 2202. [Abstract] [Full Text] [PDF]

				D. T. Fritz, S. Jiang, J. Xu, and M. B. Rogers A Polymorphism in a Conserved Posttranscriptional Regulatory Motif Alters Bone Morphogenetic Protein 2 (BMP2) RNA:Protein Interactions Mol. Endocrinol., July 1, 2006; 20(7): 1574 - 1586. [Abstract] [Full Text] [PDF]

				I. Rigoutsos, T. Huynh, K. Miranda, A. Tsirigos, A. McHardy, and D. Platt Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes PNAS, April 25, 2006; 103(17): 6605 - 6610. [Abstract] [Full Text] [PDF]

				P. D. Keightley, G. V. Kryukov, S. Sunyaev, D. L. Halligan, and D. J. Gaffney Evolutionary constraints in conserved nongenic sequences of mammals Genome Res., October 1, 2005; 15(10): 1373 - 1378. [Abstract] [Full Text] [PDF]

				M. Sironi, G. Menozzi, G. P. Comi, R. Cagliani, N. Bresolin, and U. Pozzoli Analysis of intronic conserved elements indicates that functional complexity might represent a major source of negative selection on non-coding sequences Hum. Mol. Genet., September 1, 2005; 14(17): 2533 - 2546. [Abstract] [Full Text] [PDF]

				G. V Kryukov, S. Schmidt, and S. Sunyaev Small fitness effect of mutations in highly conserved non-coding regions Hum. Mol. Genet., August 1, 2005; 14(15): 2221 - 2229. [Abstract] [Full Text] [PDF]

				G. Bejerano, M. Pheasant, I. Makunin, S. Stephen, W. J. Kent, J. S. Mattick, and D. Haussler Ultraconserved Elements in the Human Genome Science, May 28, 2004; 304(5675): 1321 - 1325. [Abstract] [Full Text] [PDF]