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Published online before print March 13, 2001, 10.1101/gr.GR-1603R
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Vol. 11, Issue 4, 519-530, April 2001

REPORTS
Characterization of Clustered MHC-Linked Olfactory Receptor Genes in Human and Mouse

Ruth M. Younger,1 Claire Amadou,2,5 Graeme Bethel,1 Anke Ehlers,3 Kirsten Fischer Lindahl,2 Simon Forbes,4 Roger Horton,1 Sarah Milne,1 Andrew J. Mungall,1 John Trowsdale,4 Armin Volz,3 Andreas Ziegler,3 and Stephan Beck1,6

1 The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK; 2 Howard Hughes Medical Institute, Center for Immunology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9050, USA; 3 Institut für Immungenetik, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, 14050 Berlin, Germany; 4 Cambridge University, Department of Pathology, Immunology Division, Cambridge CB2 1QP, UK

Olfactory receptor (OR) loci frequently cluster and are present on most human chromosomes. They are members of the seven transmembrane receptor (7-TM) superfamily and, as such, are part of one of the largest mammalian multigene families, with an estimated copy number of up to 1000 ORs per haploid genome. As their name implies, ORs are known to be involved in the perception of odors and possibly also in other, nonolfaction-related, functions. Here, we report the characterization of ORs that are part of the MHC-linked OR clusters in human and mouse (partial sequence only). These clusters are of particular interest because of their possible involvement in olfaction-driven mate selection. In total, we describe 50 novel OR loci (36 human, 14 murine), making the human MHC-linked cluster the largest sequenced OR cluster in any organism so far. Comparative and phylogenetic analyses confirm the cluster to be MHC-linked but divergent in both species and allow the identification of at least one ortholog that will be useful for future regulatory and functional studies. Quantitative feature analysis shows clear evidence of duplications of blocks of OR genes and reveals the entire cluster to have a genomic environment that is very different from its neighboring regions. Based on in silico transcript analysis, we also present evidence of extensive long-distance splicing in the 5'-untranslated regions and, for the first time, of alternative splicing within the single coding exon of ORs. Taken together with our previous finding that ORs are also polymorphic, the presented data indicate that the expression, function, and evolution of these interesting genes might be more complex than previously thought.

[The sequence data described in this paper have been submitted to the EMBL nucleotide data library under accession nos. Z84475, Z98744, Z98745, AL021807, AL021808, AL022723, AL022727, AL031893, AL035402, AL035542, AL050328, AL050339, AL078630, AL096770, AL121944, AL133160, and AL133267.]

5 Present address: CNRS UPR2163, CHU Purpan, 31300 Toulouse, France.

6 Corresponding author.

11:519-530 ©2001 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/01 $5.00
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