Human olfaction: from genomic variation to phenotypic diversity
Abstract
The sense of smell is a complex molecular device, encompassing several hundred olfactory receptor proteins (ORs). These receptors, encoded by the largest human gene superfamily, integrate odorant signals into an accurate 'odor image' in the brain. Widespread phenotypic diversity in human olfaction is, in part, attributable to prevalent genetic variation in OR genes, owing to copy number variation, deletion alleles and deleterious single nucleotide polymorphisms. The development of new genomic tools, including next generation sequencing and CNV assays, provides opportunities to characterize the genetic variations of this system. The advent of large-scale functional screens of expressed ORs, combined with genetic association studies, has the potential to link variations in ORs to human chemosensory phenotypes. This promises to provide a genome-wide view of human olfaction, resulting in a deeper understanding of personalized odor coding, with the potential to decipher flavor and fragrance preferences.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Compared with a recent individual-genome survey, the set had a similar deletion size distribution but different size distributions for other structural-variant classes, reflecting ascertainment differences.
“we also compared our set to a recent survey of SVs in an individual genome37 based on capillary sequencing and array-based analyses24, and observed a similar size distribution for deletions, but differences in the size distributions of other SV classes, reflecting underlying differences in SV ascertainment”
From Mapping copy number variation by population-scale genome sequencing (2011) · cites this paper as [37]
Cites
High-Resolution Crystal Structure of an Engineered Human β 2 -Adrenergic G Protein–Coupled Receptor
Cherezov, V., Rosenbaum, D. M., Hanson, M. A., Rasmussen, S. G. F., Thian, F. S., Kobilka, T. S., Choi, H., Kühn, P., Weis, W. I., Kobilka, B. K., et al. (2007) · Science · doi:10.1126/science.1150577 · Cited by 3,280 · see citing works
The impact of next-generation sequencing technology on genetics
Mardis, E. R. (2008) · Trends in Genetics · doi:10.1016/j.tig.2007.12.007 · Cited by 2,050 · see citing works
The complete genome of an individual by massively parallel DNA sequencing
Wheeler, D. A., Srinivasan, M., Egholm, M., Shen, Y., Chen, L., McGuire, A., He, W., Chen, Y.-J., Makhijani, V., Roth, G. T., et al. (2008) · Nature · doi:10.1038/nature06884 · Cited by 1,838 · see citing works
The Diploid Genome Sequence of an Individual Human
Levy, S., Sutton, G., Ng, P. C., Feuk, L., Halpern, A. L., Walenz, B. P., Axelrod, N., Huang, J., Kirkness, E. F., Denisov, G., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050254 · Cited by 1,778 · see citing works
Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier
Liberman, M. C., Gao, J., He, D. Z. Z., Wu, X., Jia, S., & Zuo, J. (2002) · Nature · doi:10.1038/nature01059 · Cited by 931 · see citing works
The diploid genome sequence of an Asian individual
Wang, J., Wang, W., Li, R., Li, Y., Tian, G., Goodman, L., Fan, W., Zhang, J., Li, J., Zhang, J., et al. (2008) · Nature · doi:10.1038/nature07484 · Cited by 924 · see citing works
Genome analysis of the platypus reveals unique signatures of evolution
paper, A. L. O. A. A. T. A. A. A. T. E. O. T. (2008) · Nature · doi:10.1038/nature06936 · Cited by 719 · see citing works
The Complete Human Olfactory SubgenomePreprint
Glusman, G., Yanai, I., Rubin, I., & Lancet, D. (2001) · Genome Research · doi:10.1101/gr.171001 · Cited by 697 · see citing works
Self-citationGenes and ligands for odorant, vomeronasal and taste receptors
Mombaerts, P. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1365 · Cited by 693 · see citing works
Genetic variation in a human odorant receptor alters odour perception
Keller, A., Zhuang, H., Chi, Q., Vosshall, L. B., & Matsunami, H. (2007) · Nature · doi:10.1038/nature06162 · Cited by 661 · see citing works
The evolution of animal chemosensory receptor gene repertoires: roles of chance and necessity
Nei, M., Niimura, Y., & Nozawa, M. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2480 · Cited by 626 · see citing works
Mice Deficient in Golf Are Anosmic
Belluscio, L., Gold, G. H., Nemes, A., & Axel, R. (1998) · Neuron · doi:10.1016/s0896-6273(00)80435-3 · Cited by 563 · see citing works
Odor Coding by a Mammalian Receptor Repertoire
Saito, H., Chi, Q., Zhuang, H., Matsunami, H., & Mainland, J. D. (2009) · Science Signaling · doi:10.1126/scisignal.2000016 · Cited by 563 · see citing works
Brunet, L. J., Gold, G. H., & Ngai, J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80200-7 · Cited by 510 · see citing works
Wong, S. T., Trinh, K., Hacker, B., Chan, G. C. K., Lowe, G., Gaggar, A., Xia, Z., Gold, G. H., & Storm, D. R. (2000) · Neuron · doi:10.1016/s0896-6273(00)00060-x · Cited by 470 · see citing works
Olfactory disorders and their consequences for quality of life
Hummel, T. R., & Nordin, S. (2004) · Acta Oto-Laryngologica · doi:10.1080/00016480410022787 · Cited by 398 · see citing works
The human olfactory receptor repertoire
Zozulya, S., Echeverri, F., & Nguyen, T. (2001) · Genome biology · doi:10.1186/gb-2001-2-6-research0018 · Cited by 357 · see citing works
Extensive Gains and Losses of Olfactory Receptor Genes in Mammalian Evolution
Niimura, Y., & Nei, M. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000708 · Cited by 341 · see citing works
National Geographic Smell Survey: Effects of Age Are Heterogenous
Wysocki, C., & Gilbert, A. (1989) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1989.tb20966.x · Cited by 336 · see citing works
Katada, S., Hirokawa, T., Oka, Y., Suwa, M., & Touhara, K. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4723-04.2005 · Cited by 318 · see citing works
Human specific loss of olfactory receptor genes
Gilad, Y., Man, O., Pääbo, S., & Lancet, D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0535697100 · Cited by 310 · see citing works
Self-citationAbility to perceive androstenone can be acquired by ostensibly anosmic people.
Wysocki, C. J., Dorries, K. M., & Beauchamp, G. K. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.20.7976 · Cited by 293 · see citing works
Genetic Variation in an Individual Human Exome
Ng, P. C., Levy, S., Huang, J., Stockwell, T. B., Walenz, B. P., Li, K., Axelrod, N., Busam, D., Strausberg, R. L., & Venter, J. C. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000160 · Cited by 288 · see citing works
Chemotopic odorant coding in a mammalian olfactory system
Johnson, B. A., & Leon, M. (2007) · The Journal of Comparative Neurology · doi:10.1002/cne.21396 · Cited by 286 · see citing works
Ability to smell androstenone is genetically determined.
Wysocki, C. J., & Beauchamp, G. K. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.15.4899 · Cited by 279 · see citing works
One neuron–one receptor rule in the mouse olfactory system
Serizawa, S., Miyamichi, K., & Sakano, H. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.09.006 · Cited by 260 · see citing works
Different noses for different people
Menashe, I., Man, O., Lancet, D., & Gilad, Y. (2003) · Nature Genetics · doi:10.1038/ng1160 · Cited by 229 · see citing works
Self-citationGenetic Elucidation of Human Hyperosmia to Isovaleric Acid
Menashe, I., Abaffy, T., Hasin-Brumshtein, Y., Goshen, S., Yahalom, V., Luetje, C. W., & Lancet, D. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050284 · Cited by 218 · see citing works
Self-citationOlfactory sensitivity: Reliability, generality, and association with aging.
Cain, W. S., & Gent, J. F. (1991) · Journal of Experimental Psychology Human Perception & Performance · doi:10.1037//0096-1523.17.2.382 · Cited by 197 · see citing works
Extending genome-wide association studies to copy-number variation
McCarroll, S. A. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn282 · Cited by 196 · see citing works
Complaints of olfactory disorders: epidemiology, assessment and clinical implications
Nordin, S., & Brämerson, A. (2008) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0b013e3282f3f473 · Cited by 173 · see citing works
Lancet, D., Sadovsky, E., & Seidemann, E. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.8.3715 · Cited by 160 · see citing works
Self-citationGenomic drift and copy number variation of sensory receptor genes in humans
Nozawa, M., Kawahara, Y., & Nei, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709956104 · Cited by 157 · see citing works
Spatiotemporal representations in the olfactory system
Schaefer, A. T., & Margrie, T. W. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.01.001 · Cited by 155 · see citing works
Prediction of the odorant binding site of olfactory receptor proteins by human–mouse comparisons
Man, O., Gilad, Y., & Lancet, D. (2003) · Protein Science · doi:10.1110/ps.03296404 · Cited by 155 · see citing works
Self-citationOlfactory sensitivity: Reliability, generality, and association with aging.
Cain, W. S., & Gent, J. F. (1991) · Journal of Experimental Psychology Human Perception & Performance · doi:10.1037/0096-1523.17.2.382 · Cited by 147 · see citing works
Extensive Copy-Number Variation of the Human Olfactory Receptor Gene Family
Young, J. M., Endicott, R. M., Parghi, S. S., Walker, M., Kidd, J. M., & Trask, B. J. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.07.005 · Cited by 142 · see citing works
Kishida, T., Kubota, S., Shirayama, Y., & Fukami, H. (2007) · Biology Letters · doi:10.1098/rsbl.2007.0191 · Cited by 141 · see citing works
A comparison of the human and chimpanzee olfactory receptor gene repertoiresPreprint
Gilad, Y., Man, O., & Glusman, G. (2005) · Genome Research · doi:10.1101/gr.2846405 · Cited by 138 · see citing works
Sharon, D., Glusman, G., Pilpel, Y., Khen, M., Grützner, F., Haaf, T., & Lancet, D. (1999) · Genomics · doi:10.1006/geno.1999.5900 · Cited by 121 · see citing works
Self-citationOdour-Blindness to Musk: Simple Recessive Inheritance
WHISSELL-BUECHY, D., & Amoore, J. E. (1973) · Nature · doi:10.1038/242271a0 · Cited by 118 · see citing works
High-Resolution Copy-Number Variation Map Reflects Human Olfactory Receptor Diversity and Evolution
Hasin-Brumshtein, Y., Olender, T., Khen, M., Gonzaga-Jauregui, C. G., Kim, P. M., Urban, A. E., Snyder, M. P., Gerstein, M., Lancet, D., & Korbel, J. O. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000249 · Cited by 114 · see citing works
Self-citationSimilar Numbers but Different Repertoires of Olfactory Receptor Genes in Humans and Chimpanzees
Go, Y., & Niimura, Y. (2008) · Molecular Biology and Evolution · doi:10.1093/molbev/msn135 · Cited by 110 · see citing works
Importance of Achromatic Contrast in Short-Range Fruit Foraging of Primates
Hiramatsu, C., Melin, A. D., Aureli, F., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003356 · Cited by 110 · see citing works
Gilbert, A. N., & Wysocki, C. J. (1987) · National geographic/The complete National geographic/The National geographic magazine · Cited by 108 · see citing works
Measurement of Specific Anosmia
Amoore, J. E., Venstrom, D., & Davis, A. R. (1968) · Perceptual and Motor Skills · doi:10.2466/pms.1968.26.1.143 · Cited by 105 · see citing works
Korbel, J. O., Kim, P. M., Chen, X., Urban, A. E., Weissman, S. M., Snyder, M. P., & Gerstein, M. (2008) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2008.02.005 · Cited by 105 · see citing works
Hoffmann, C., Zürn, A., Bünemann, M., & Lohse, M. J. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707615 · Cited by 84 · see citing works
Human Odor Detectability: New Methodology Used to Determine Threshold and Variation
Walker, J. C. (2003) · Chemical Senses · doi:10.1093/chemse/bjg075 · Cited by 75 · see citing works
Specific anosmia in the laboratory mouse
Wysocki, C. J., Whitney, G., & Tucker, D. M. (1977) · Behavior Genetics · doi:10.1007/bf01066005 · Cited by 72 · see citing works
Olfactory dysfunction and its measurement in the clinic and workplace
Doty, R. L. (2006) · International Archives of Occupational and Environmental Health · doi:10.1007/s00420-005-0055-6 · Cited by 69 · see citing works
The genetic basis for specific anosmia to isovaleric acid in the mouse
Griff, I. C., & Reed, R. R. (1995) · Cell · doi:10.1016/0092-8674(95)90118-3 · Cited by 65 · see citing works
Keller, A., & Vosshall, L. B. (2004) · Current Biology · doi:10.1016/j.cub.2004.09.066 · Cited by 65 · see citing works
Gibbons, B. (1986) · National geographic/The complete National geographic/The National geographic magazine · Cited by 65 · see citing works
Congenital Lack of Olfactory Ability
Leopold, D. A., Hornung, D. E., & Schwob, J. E. (1992) · Annals of Otology Rhinology & Laryngology · doi:10.1177/000348949210100306 · Cited by 63 · see citing works
Deorphanizing vertebrate olfactory receptors: Recent advances in odorant-response assays
Touhara, K. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.05.020 · Cited by 61 · see citing works
Searching for the Ligands of Odorant Receptors
Malnic, B. (2007) · Molecular Neurobiology · doi:10.1007/s12035-007-0013-2 · Cited by 59 · see citing works
Effect of Environmental Pollutants on Taste and Smell
Schiffman, S. S., & Nagle, H. T. (1992) · Otolaryngology · doi:10.1177/019459989210600613 · Cited by 57 · see citing works
A Review of Kallmann Syndrome: Genetics, Pathophysiology, and Clinical Management
Fechner, A. J., Fong, S., & McGovern, P. G. (2008) · Obstetrical & Gynecological Survey · doi:10.1097/ogx.0b013e3181641278 · Cited by 57 · see citing works
Ancient genomic architecture for mammalian olfactory receptor clusters
Aloni, R., Olender, T., & Lancet, D. (2006) · Genome Biology · doi:10.1186/gb-2006-7-10-r88 · Cited by 56 · see citing works
Self-citationCo-regulation of a large and rapidly evolving repertoire of odorant receptor genes
Kambere, M. B., & Lane, R. P. (2007) · BMC Neuroscience · doi:10.1186/1471-2202-8-s3-s2 · Cited by 55 · see citing works
Evidence for genetic determination in human twins of olfactory thresholds for a standard odorant
Gross‐Isseroff, R., Ophir, D., Bartana, A., Voet, H., & Lancet, D. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90347-a · Cited by 53 · see citing works
Self-citationA probabilistic classifier for olfactory receptor pseudogenes
Menashe, I., Aloni, R., & Lancet, D. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-393 · Cited by 52 · see citing works
Self-citationSpecific anosmia to l -carvone: the minty primary odour
Pelosi, P., & Viti, R. (1978) · Chemical Senses · doi:10.1093/chemse/3.3.331 · Cited by 52 · see citing works
Human SNPs resulting in premature stop codons and protein truncation
Savas, S., Tüzmen, Ş., & Özçelik, H. (2006) · Human Genomics · doi:10.1186/1479-7364-2-5-274 · Cited by 44 · see citing works
Genetic component of identification, intensity and pleasantness of odours: a Finnish family study
Knaapila, A., Keskitalo, K., Kallela, M., Wessman, M., Sammalisto, S., Hiekkalinna, T., Palotie, A. V., Peltonen, L., Tuorila, H., & Perola, M. (2007) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201804 · Cited by 42 · see citing works
Knaapila, A., Tuorila, H., Silventoinen, K., et al. (2008) · Behavior Genetics · doi:10.1007/s10519-008-9211-6 · Cited by 40 · see citing works
Androstadienone odor thresholds in adolescents.
Hummel, T., Krone, F., Lundström, J., & Bartsch, O. (2005) · Hormones and Behavior · doi:10.1016/j.yhbeh.2004.10.007 · Cited by 39 · see citing works
Feldmesser, E., Bercovich, D., Avidan, N., et al. (2006) · Chemical Senses · doi:10.1093/chemse/bjl032 · Cited by 39 · see citing works
McNeill, E., Ramakrishnan, Y., & Carrie, S. (2007) · The Journal of Laryngology & Otology · doi:10.1017/s0022215107006615 · Cited by 36 · see citing works
Slyke, D. D. V. (1918) · Science · doi:10.1126/science.48.1238.298-a · Cited by 27 · see citing works
Zibrowski, E. M., & Robertson, J. M. (2005) · Occupational Medicine · doi:10.1093/occmed/kqi190 · Cited by 25 · see citing works
Isolated congenital anosmia locus maps to 18p11.23-q12.2
Ghadami, M., Morovvati, S., Majidzadeh‐A, K., et al. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.015313 · Cited by 23 · see citing works
Valle, D. L. (2004) · The American Journal of Human Genetics · doi:10.1086/382790 · Cited by 21 · see citing works
A Framework for Exploring Functional Variability in Olfactory Receptor Genes
Man, O., Willhite, D. C., Crasto, C. J., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000682 · Cited by 15 · see citing works
Hyperosmia and depression following exposure to toxic vapors
Henkin, R. I. (1990) · JAMA · doi:10.1001/jama.264.21.2803 · Cited by 14 · see citing works
Receptors, Circuits, and Behaviors: New Directions in Chemical Senses
Katz, D. B., Matsunami, H., Rinberg, D. A., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3613-08.2008 · Cited by 13 · see citing works
Henkin, R. I. (1990) · JAMA · doi:10.1001/jama.1990.03450210103043 · Cited by 11 · see citing works
Methotrexate, hyperosmia, and migraine
Zargari, O. (2006) · Dermatology Online Journal · doi:10.5070/d34pt9b52w · Cited by 8 · see citing works
Unlike Reaction of Different Individuals to Fragrance in Verbena Flowers
Blakeslee, A. F. (1918) · Science · doi:10.1126/science.48.1238.298.b · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mapping copy number variation by population-scale genome sequencing
1000 Genomes Project, Mills, R. E., Walter, K., Stewart, C., Handsaker, R. E., Chen, K., Alkan, C., Abyzov, A., Yoon, S. C., Ye, K., et al. (2011) · Nature · doi:10.1038/nature09708 · Cited by 1,140 · see citing works
A copy number variation map of the human genome
Zarrei, M., MacDonald, J. R., Merico, D., & Scherer, S. W. (2015) · Nature Reviews Genetics · doi:10.1038/nrg3871 · Cited by 921 · see citing works
A Pilot Detection and Associate Study of Gene Presence-Absence Variation in Holstein Cattle
Boschiero, C., Neupane, M., Yang, L., Schroeder, S. G., Tuo, W., Ma, L., Baldwin, R. L., Van Tassell, C. P., & Liu, G. E. (2024) · Animals · doi:10.3390/ani14131921 · Cited by 5 · see citing works
- Authors
- Hasin-Brumshtein, Y., Lancet, D., & Olender, T.
- Affiliations
- Crown Human Genome Center (IL)
- Corresponding author
- Lancet, Doron
- Venue
- Trends in Genetics
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 25
- Issue
- 4
- Pages
- 178-184
- ISSN
- 0168-9525 (ISSN-L)
- OpenAlex
- W2035403293
- Cited by
- 176
- References
- 80
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 10 · 2023: 9 · 2022: 14 · 2021: 11 · 2020: 10 · 2019: 9 · 2018: 10 · 2017: 10 · 2016: 16 · 2015: 10 · 2014: 12 · 2013: 11 · 2012: 12
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Trends in Genetics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- human olfaction, olfactory receptor genes, copy number variation, single nucleotide polymorphisms, deletion alleles, olfaction, genetic association studies
- MeSH terms
- Alleles, Humans, Models, Biological, Models, Genetic, Phenotype, Phylogeny, Polymorphism, Genetic, Smell, Genetic Variation, Genome, Human, Receptors, Odorant, Gene Dosage, Evolution, Molecular, Polymorphism, Single Nucleotide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
