Biomedical subjects

A Sosinsky

Publications and source records attributed to A Sosinsky.

3 recordsLinked to original sources

PubMed2000

The genomic structure of human olfactory receptor genes.

The genomic and cDNA structures were studied for eight human olfactory receptor (OR) genes within the chromosome 17p13.3 cluster. A common gene structure was revealed, which included an approximately 1-kb intronless coding region terminated by a signal for polyadenylation and a variable number of upstream noncoding exons. The latter were found to be alternatively spliced, giving rise to different isoforms of OR mRNA. While the initial exons mostly agreed with previous computer predictions and were conserved within OR subfamilies, other upstream exons were novel and idiosyncratic. In some cases, repetitive sequences were involved in the generation of splice sites and putative transcription control elements. Such gene structure is consistent with early repertoire enhancement by retrogene generation, which was likely followed by extensive genomic duplication. Each OR gene had a unique signature of transcription factor elements, consistent with a combinatorial expression control mechanism.

Alternative Splicing↗

PubMed2000

Sequence, structure, and evolution of a complete human olfactory receptor gene cluster.

The olfactory receptor (OR) gene cluster on human chromosome 17p13.3 was subjected to mixed shotgun automated DNA sequencing. The resulting 412 kb of genomic sequence include 17 OR coding regions, 6 of which are pseudogenes. Six of the coding regions were discovered only upon genomic sequencing, while the others were previously reported as partial sequences. A comparison of DNA sequences in the vicinity of the OR coding regions revealed a common gene structure with an intronless coding region and at least one upstream noncoding exon. Potential gene control regions including specific pyrimidine:purine tracts and Olf-1 sites have been identified. One of the pseudogenes apparently has evolved into a CpG island. Four extensive CpG islands can be discerned within the cluster, not coupled to specific OR genes. The cluster is flanked at its telomeric end by an unidentified open reading frame (C17orf2) with no significant similarity to any known protein. A high proportion of the cluster sequence (about 60%) belongs to various families of interspersed repetitive elements, with a clear predominance of LINE repeats. The OR genes in the cluster belong to two families and seven subfamilies, which show a relatively high degree of intermixing along the cluster, in seemingly random orientations. This genomic organization may be best accounted for by a complex series of evolutionary events.

Base Sequence↗

PubMed1998

Molecular biology of olfactory receptors.

OR proteins bind odorant ligands and transmit a G-protein-mediated intracellular signal, resulting in generation of an action potential. The accumulation of DNA sequences of hundreds of OR genes provides an opportunity to predict features related to their structure, function and evolutionary diversification. The OR repertoire has evolved a variable ligand-binding site that ascertains recognition of multiple odorants, coupled to constant regions that mediate the cAMP-mediated signal transduction. The cellular second messenger underlies the responses to diverse odorants through the direct gating of olfactory-specific cation channels. This situation necessitates a mechanism of cellular exclusion, whereby each sensory neuron expresses only one receptor type, which in turn influences axonal projections. A 'synaptic image' of the OR repertoire thus encodes the detected odorant in the central nervous system.

Animals↗