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

Ehlers, Anke; Beck, Stephan; Forbes, Simon; Trowsdale, John; Volz, Armin; Younger, Ruth; Ziegler, Andreas

doi:10.1101/gr.10.12.1968

Cited by 69 publications

(73 citation statements)

References 47 publications

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“…hs6M1-14P, for example, was considered a pseudogene solely because of the missing conventional initiator ATG (6), but again, the alternative start codon at position 79 could give rise to a 5-TM fragment. In addition, OR gene polymorphism is expected to increase the complexity even further (5,44). Therefore, the accumulation of mutations during primate evolution does not necessarily reduce the number of OR specificities as postulated (73) but might have led to new functional properties of OR.…”

Section: Discussionmentioning

confidence: 99%

“…2 Therefore, we have used the original nomenclature under which these OR genes were first published (5,30).…”

Section: Nomenclature For or Genes-the Human Nomenclature Committeementioning

confidence: 99%

“…However, it appears that fewer than 350 OR genes (ϳ40%) have an intact, undisrupted open reading frame (2) coding for all seven transmembrane (TM) domains that are characteristic for these G-protein-coupled receptors (3,4). In addition, there is a high degree of OR polymorphism producing a variable functional repertoire with genes that are nonfunctional in one haplotype and functional in another (5). Despite these interindividual differences, the coding regions of vertebrate OR genes usually have a length of ϳ1 kb and are not interrupted by introns, although some expressed sequence tag data suggest that splicing within the predicted open reading frame may occur, producing a protein with only five transmembrane domains (6).…”

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confidence: 99%

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Complex Transcription and Splicing of Odorant Receptor Genes

Volz

Ehlers

Younger

et al. 2003

Journal of Biological Chemistry

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Human major histocompatibility (human leucocyte antigen (HLA)) complex-linked odorant receptor (OR) genes are among the best characterized OR genes in the human genome. In addition to their functions as odorant receptors in olfactory epithelium, they have been suggested to play a role in the fertilization process. Here, we report the first in-depth analysis of their expression and regulation within testicular tissue. Sixteen HLA-linked OR and three non-HLA-linked OR were analyzed. One OR gene (hs6M1-16, in positive transcriptional orientation) exhibited six different transcriptional start sites combined with extensive alternative splicing within the 5 -untranslated region, the coding exon, and the 3 -untranslated region. Long distance splicing, exon sharing, and premature polyadenylation were features of another three OR loci (hs6M1-18, -21, and -27, all upstream of hs6M1-16, but in negative transcriptional orientation). Determination of the transcriptional start sites of these OR genes identified a region of 81 bp with potential bi-directional transcriptional activity. The results demonstrate that HLA-linked OR genes are subject to unusually complex transcriptional regulatory mechanisms.

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Section: Discussionmentioning

confidence: 99%

“…2 Therefore, we have used the original nomenclature under which these OR genes were first published (5,30).…”

Section: Nomenclature For or Genes-the Human Nomenclature Committeementioning

confidence: 99%

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confidence: 99%

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Complex Transcription and Splicing of Odorant Receptor Genes

Volz

Ehlers

Younger

et al. 2003

Journal of Biological Chemistry

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“…In contrast, the mutations of NOD-2/ CARD-15 associated with Blau syndrome, as well as earlyonset sarcoidosis, are located in the NOD domain and lead to increased constitutive NF-B activity in the absence of MDP (2). The similarity of the location of gain-of-function mutations in CIAS1 in CINCA syndrome and NOD-2/CARD-15 in Blau syndrome/early-onset sarcoidosis has been noted by Chamaillard et al (3). We suggest, therefore, that the CIAS1 mutations in the LRR region should be carefully evaluated by functional analysis to identify the mutations responsible for the disease.…”

mentioning

confidence: 99%

“…There are 34 HLA-linked OR genes within the extended HLA complex, of which at least half are potentially functional (2,3). All HLA-linked OR loci tested so far are polymorphic (3).…”

mentioning

confidence: 99%