Abstracts - Association for Chemoreception Sciences
Abstracts - Association for Chemoreception Sciences
Abstracts - Association for Chemoreception Sciences
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#13 SYMPOSIUM -<br />
GENETICS OF HUMAN OLFACTION<br />
Next generation genomics of human olfactory variation<br />
Doron Lancet 1 , Yehudit Hasin 1 , Sebastian Waszak 2 , Ifat Keydar 1 ,<br />
Miriam Khen 1 , Charles J. Wysocki 3 , Edna Ben-Asher 1 , Yoav<br />
Gilad 4 , Jan O. Korbel 2 , Tsviya Olender 1<br />
1<br />
The Weizmann Institute of Science Rehovot, Israel, 2 European<br />
Molecular Biology Laboratory Heidelberg, Germany, 3 Monell<br />
Chemical Senses Center Philadelphia, PA, USA, 4 University of<br />
Chicago Chicago, IL, USA<br />
We have previously identified 75 cases of human OR deleterious<br />
alleles, stemming from frame-disrupting single nucleotide<br />
polymorphisms (SNPs) and null copy number variations (CNVs).<br />
This provides a genomic infrastructure <strong>for</strong> associating OR<br />
genotypes to olfactory phenotypes. To augment such a list and<br />
extend it beyond OR coding region losses, we now apply the<br />
novel Next Generation Sequencing (NGS) method to genome and<br />
transcriptome sequences. Test analysis of 100 intact OR genes in<br />
20 individuals indicated a capacity to discover 19 additional<br />
disrupting SNPs (segregating pseudogenes, SPGs) with up to 4 bp<br />
deletions. More comprehensively, scrutinizing the 1000 Genomes<br />
Project (1000GP) data, we have identified ~3500 novel SNPs,<br />
including 78 new disrupting ones. In the realm of CNVs, we<br />
developed CopySeq, a new algorithm <strong>for</strong> large-scale<br />
determination of accurate copy-number genotypes and applied it<br />
to the low-sequence-depth 1000GP data of 150 individuals. We<br />
observed a wide range of OR copy-number states (0-9 copies),<br />
and are contemplating the possible phenotype at the high copy<br />
number end. For OR deletions, we found 95 novel loci and<br />
obtained good estimates <strong>for</strong> their population prevalence, including<br />
clear paucity in African-Americans. About 10% of the functional<br />
ORs have a deletion allele and ~25% of all individuals show at<br />
least one homozygous deletion. In parallel, olfactory epithelial<br />
NGS transcriptome analysis is unraveling novel mutation targets,<br />
includes upstream splice junctions, as well as a verified and<br />
augmented list of human olfactory transduction genes. The<br />
emerging variation map of the olfactory gene universe will assist<br />
in explaining the full extent of olfactory phenotype variations,<br />
covering both odorant-specific differences as well as general<br />
chemosensory threshold diversity. Acknowledgements: Supported<br />
by NIH grant RO1 DC00298 to CJW and the Crown Human<br />
Genome Center at the Weizmann Institute.<br />
#14 SYMPOSIUM -<br />
GENETICS OF HUMAN OLFACTION<br />
Genetics of Olfactory Perception in Humans<br />
Leslie B Vosshall 1, 2<br />
1<br />
The Rockefeller University New York, NY, USA, 2 Howard<br />
Hughes Medical Institute New York, NY, USA<br />
pleasantness of more than 100 different odorous stimuli. Strong<br />
correlations were found <strong>for</strong> the perception of different aspects of<br />
the same stimulus and <strong>for</strong> the perception of the same odor at<br />
different concentrations. The perception of structurally similar<br />
odors like androstenone and androstadienone, showed strong<br />
correlations, validating our approach. The same was found <strong>for</strong><br />
structurally diverse yet perceptually similar odors like the musky<br />
odors ethylene brassylate, pentadecalactone, and galaxolide. An<br />
unbiased analysis of the correlations also uncovered new<br />
connections between odors that are neither perceptually nor<br />
structurally similar, but presumably are processed by overlapping<br />
neuronal substrates. Taken together, these findings allow us to<br />
group human subjects into perceptual phenotypes based on their<br />
odor perception. We previously correlated differences in the<br />
perceived pleasantness and intensity of androstenone and<br />
androstadienone with genetic variation in the OR7D4 gene and<br />
suggest that the perceptual phenotypes discovered here may<br />
correspond to odorant receptor gene genotypes.<br />
Acknowledgements: Work in my laboratory is supported by<br />
HHMI and NIH/NIDCD.<br />
#15 PRESIDENTIAL SYMPOSIUM:<br />
NEUROTRANSMITTERS AND<br />
NEUROMODULATORS IN THE TASTE BUD<br />
Cells, signals, and synapses in mammalian taste buds<br />
Stephen Roper<br />
Department of Physiology & Biophysics, and Program in<br />
Neuroscience, Miller School of Medicine, University of Miami,<br />
Miami, FL 33136<br />
A taste bud is a population of 50 to 100 interacting cells that<br />
process gustatory stimuli and excite one or more primary sensory<br />
afferent fibers that innervate the taste bud. Some taste cells within<br />
the population respond to sweet, bitter or umami compounds,<br />
others to sour (H+), and yet others to salty (Na+). Fats (as fatty<br />
acids) may also stimulate selected subsets of cells within the<br />
population. Gustatory stimulation at the taste pore initiates a<br />
series of synaptic interactions within the population of taste cells,<br />
involving the exchange of excitatory and inhibitory signals, and<br />
including feedback signaling. My laboratory has focused on<br />
identifying the synaptic transmitters that underlie this exchange of<br />
signals in the taste bud. We are investigating which cells release<br />
neurotransmitters, what is(are) the transmitter(s), where do those<br />
transmitters act within the taste bud, and ultimately, how are the<br />
interactions among the different cells orchestrated to produce a<br />
meaningful signal output that can be transmitted to the sensory<br />
afferent fibers. Our findings to date indicate that considerable<br />
synaptic integration takes place during taste reception; taste buds<br />
appear to be conducting a remarkable extent of signal processing<br />
during gustatory stimulation.<br />
Odorant receptors represent the largest gene superfamily in the<br />
human genome and. account <strong>for</strong> the diversity of odors that we can<br />
detect, yet it is not known how the olfactory system encodes an<br />
olfactory percept. Because humans can sense many more odors<br />
that than the number of odorant receptor genes they possess,<br />
there must be some overlap in the neuronal substrates processing<br />
different odor stimuli. We analyzed correlations between different<br />
aspects of odor perception <strong>for</strong> two concentrations of 66 different<br />
odors to study how one aspect of olfactory perception predicts<br />
other aspects. We collected olfactory detection thresholds <strong>for</strong><br />
several odors and subjective assessments of the intensity and<br />
<strong>Abstracts</strong> are printed as submitted by the author(s)<br />
<strong>Abstracts</strong> | 11