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Vol. 10, Issue 12, 1968-1978, December 2000

LETTER
MHC-Linked Olfactory Receptor Loci Exhibit Polymorphism and Contribute to Extended HLA/OR-Haplotypes

Anke Ehlers,1 Stephan Beck,2 Simon A. Forbes,3 John Trowsdale,3 Armin Volz,1 Ruth Younger,2 and Andreas Ziegler1,4

1 Institut für Immungenetik, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, 14050 Berlin, Germany; 2 The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK; 3 Department of Pathology, Division of Immunology, University of Cambridge, Cambridge CB2 1QP, UK

Clusters of olfactory receptor (OR) genes are found on most human chromosomes. They are one of the largest mammalian multigene families. Here, we report a systematic study of polymorphism of OR genes belonging to the largest fully sequenced OR cluster. The cluster contains 36 OR genes, of which two belong to the vomeronasal 1 (V1-OR) family. The cluster is divided into a major and a minor region at the telomeric end of the HLA complex on chromosome 6. These OR genes could be involved in MHC-related mate preferences. The polymorphism screen was carried out with 13 genes from the HLA-linked OR cluster and three genes from chromosomes 7, 17, and 19 as controls. Ten human cell lines, representing 18 different chromosome 6s, were analyzed. They were from various ethnic origins and exhibited different HLA haplotypes. All OR genes tested, including those not linked to the HLA complex, were polymorphic. These polymorphisms were dispersed along the coding region and resulted in up to seven alleles for a given OR gene. Three polymorphisms resulted either in stop codons (genes hs6M1-4P, hs6M1-17) or in a 16-bp deletion (gene hs6M1-19P), possibly leading to lack of ligand recognition by the respective receptors in the cell line donors. In total, 13 HLA-linked OR haplotypes could be defined. Therefore, allelic variation appears to be a general feature of human OR genes.

[The sequence data reported in this paper have been submitted to EMBL under accession nos. AC006137, AC004178, AJ132194, AL022727, AL031983, AL035402, AL035542, Z98744, CAB55431, AL050339, AL035402, AL096770, AL133267, AL121944, Z98745, AL021808, and AL021807.]

4 Corresponding author.

10:1968-1978 ©2000 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/00 $5.00
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