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Research Article

Individual olfactory perception reveals meaningful nonolfactory genetic information

Lavi Secundo, Kobi Snitz, Kineret Weissler, Liron Pinchover, Yehuda Shoenfeld, Ron Loewenthal, Nancy Agmon-Levin, View ORCID ProfileIdan Frumin, Dana Bar-Zvi, Sagit Shushan, and Noam Sobel
  1. aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
  2. bZabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer 5265601, Israel;
  3. cSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel;
  4. dTissue Typing Laboratory, Sheba Medical Center, Tel Hashomer 5265601, Israel

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PNAS first published June 22, 2015; https://doi.org/10.1073/pnas.1424826112
Lavi Secundo
aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
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  • For correspondence: noam.sobel@weizmann.ac.il lavisec@gmail.com
Kobi Snitz
aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
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Kineret Weissler
aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
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Liron Pinchover
aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
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Yehuda Shoenfeld
bZabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer 5265601, Israel;
cSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel;
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Ron Loewenthal
dTissue Typing Laboratory, Sheba Medical Center, Tel Hashomer 5265601, Israel
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Nancy Agmon-Levin
bZabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer 5265601, Israel;
cSackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel;
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Idan Frumin
aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
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  • ORCID record for Idan Frumin
Dana Bar-Zvi
aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
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Sagit Shushan
aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
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Noam Sobel
aDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel;
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  • For correspondence: noam.sobel@weizmann.ac.il lavisec@gmail.com
  1. Edited by John G. Hildebrand, University of Arizona, Tucson, AZ, and approved May 13, 2015 (received for review December 28, 2014)

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Significance

Cyrano de Bergerac observed that “a large nose is the mark of a witty, courteous, affable, generous and liberal man.” Here we report that individual noses, not how they look but rather how they function, indeed say a lot about a person. Each person expresses a nearly unique set of different olfactory receptor genes, and therefore may have unique olfactory perception. We developed a highly sensitive perceptual test we call the “olfactory fingerprint” that captures this variability. Individual olfactory fingerprints are therefore mirrors of individual olfactory genomes. We demonstrate that such fingerprints predict genetic features linked to the olfactory system, such as aspects of immune regulation. Thus, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.

Abstract

Each person expresses a potentially unique subset of ∼400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the “olfactory fingerprint.” Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10−10), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10−4), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10−6). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.

  • olfactory perception
  • HLA
  • MHC
  • olfactory genetics
  • autoimmunity

Footnotes

  • ↵1L.S. and K.S. contributed equally to this work.

  • ↵2To whom correspondence may be addressed. Email: noam.sobel{at}weizmann.ac.il or lavisec{at}gmail.com.
  • Author contributions: L.S., K.S., K.W., and N.S. designed research; L.S., K.S., K.W., L.P., Y.S., R.L., N.A.-L., I.F., D.B.-Z., S.S., and N.S. performed research; L.S., K.S., K.W., L.P., and N.S. analyzed data; and L.S., K.S., R.L., and N.S. wrote the paper.

  • Conflict of interest statement: The Weizmann Institute is filing for a patent on the method of olfactory fingerprinting.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1424826112/-/DCSupplemental.

Freely available online through the PNAS open access option.

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Individual olfactory perception
Lavi Secundo, Kobi Snitz, Kineret Weissler, Liron Pinchover, Yehuda Shoenfeld, Ron Loewenthal, Nancy Agmon-Levin, Idan Frumin, Dana Bar-Zvi, Sagit Shushan, Noam Sobel
Proceedings of the National Academy of Sciences Jun 2015, 201424826; DOI: 10.1073/pnas.1424826112

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Individual olfactory perception
Lavi Secundo, Kobi Snitz, Kineret Weissler, Liron Pinchover, Yehuda Shoenfeld, Ron Loewenthal, Nancy Agmon-Levin, Idan Frumin, Dana Bar-Zvi, Sagit Shushan, Noam Sobel
Proceedings of the National Academy of Sciences Jun 2015, 201424826; DOI: 10.1073/pnas.1424826112
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