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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

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