Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology
Research Article

Rare variants in axonogenesis genes connect three families with sound–color synesthesia

View ORCID ProfileAmanda K. Tilot, Katerina S. Kucera, Arianna Vino, Julian E. Asher, Simon Baron-Cohen, and View ORCID ProfileSimon E. Fisher
PNAS March 20, 2018 115 (12) 3168-3173; first published March 5, 2018; https://doi.org/10.1073/pnas.1715492115
Amanda K. Tilot
aLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, 6500 AH Nijmegen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Amanda K. Tilot
Katerina S. Kucera
aLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, 6500 AH Nijmegen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arianna Vino
aLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, 6500 AH Nijmegen, The Netherlands;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julian E. Asher
bAutism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge CB2 8AH, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon Baron-Cohen
bAutism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge CB2 8AH, United Kingdom;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon E. Fisher
aLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, 6500 AH Nijmegen, The Netherlands;
cDonders Institute for Brain, Cognition and Behaviour, Radboud University, 6500 HE Nijmegen, The Netherlands
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Simon E. Fisher
  • For correspondence: simon.fisher@mpi.nl
  1. Edited by Edward M. Hubbard, University of Wisconsin–Madison, Madison, WI, and accepted by Editorial Board Member Randolph Blake January 23, 2018 (received for review September 5, 2017)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

Our physical senses are separated not only into distinct experiences but also into specialized regions within the cerebral cortex. Synesthesia is a neurological phenomenon that causes unusual links between sensory experiences, and its molecular basis is completely unknown. We demonstrate that three families who experience color when listening to sounds are connected by rare genetic variants affecting genes that contribute to axonogenesis, a process essential for neuronal connections within and across brain regions. Multiple genes with similar activity patterns during neural development fall within parts of the genome previously linked to the condition. Our results connect synesthetes’ altered structural and functional connectivity to genes that support the development of those connections.

Abstract

Synesthesia is a rare nonpathological phenomenon where stimulation of one sense automatically provokes a secondary perception in another. Hypothesized to result from differences in cortical wiring during development, synesthetes show atypical structural and functional neural connectivity, but the underlying molecular mechanisms are unknown. The trait also appears to be more common among people with autism spectrum disorder and savant abilities. Previous linkage studies searching for shared loci of large effect size across multiple families have had limited success. To address the critical lack of candidate genes, we applied whole-exome sequencing to three families with sound–color (auditory–visual) synesthesia affecting multiple relatives across three or more generations. We identified rare genetic variants that fully cosegregate with synesthesia in each family, uncovering 37 genes of interest. Consistent with reports indicating genetic heterogeneity, no variants were shared across families. Gene ontology analyses highlighted six genes—COL4A1, ITGA2, MYO10, ROBO3, SLC9A6, and SLIT2—associated with axonogenesis and expressed during early childhood when synesthetic associations are formed. These results are consistent with neuroimaging-based hypotheses about the role of hyperconnectivity in the etiology of synesthesia and offer a potential entry point into the neurobiology that organizes our sensory experiences.

  • synaesthesia
  • synesthesia
  • perception
  • axonogenesis
  • whole-exome sequencing

Footnotes

  • ↵1S.B.-C. and S.E.F. contributed equally to this work.

  • ↵2To whom correspondence should be addressed. Email: simon.fisher{at}mpi.nl.
  • Author contributions: A.K.T., K.S.K., S.B.-C., and S.E.F. designed research; A.K.T., K.S.K., A.V., and J.E.A. performed research; A.K.T., K.S.K., A.V., and S.E.F. analyzed data; A.K.T. and S.E.F. wrote the paper; and J.E.A. and S.B.-C. collected synesthesia families.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission. E.M.H. is a guest editor invited by the Editorial Board.

  • Data deposition: The datasets generated during the current study are available upon request from The Language Archive (TLA: https://corpus1.mpi.nl/ds/asv/?0), a public data archive hosted by the Max Planck Institute for Psycholinguistics. The data are stored under the node IDs MPI1758324# and MPI1815362# and are accessible at https://hdl.handle.net/1839/00-0000-0000-001A-8756-4@view.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1715492115/-/DCSupplemental.

  • Copyright © 2018 the Author(s). Published by PNAS.

This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Rare variants in axonogenesis genes connect three families with sound–color synesthesia
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Rare variants in axonogenesis genes connect three families with sound–color synesthesia
Amanda K. Tilot, Katerina S. Kucera, Arianna Vino, Julian E. Asher, Simon Baron-Cohen, Simon E. Fisher
Proceedings of the National Academy of Sciences Mar 2018, 115 (12) 3168-3173; DOI: 10.1073/pnas.1715492115

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Rare variants in axonogenesis genes connect three families with sound–color synesthesia
Amanda K. Tilot, Katerina S. Kucera, Arianna Vino, Julian E. Asher, Simon Baron-Cohen, Simon E. Fisher
Proceedings of the National Academy of Sciences Mar 2018, 115 (12) 3168-3173; DOI: 10.1073/pnas.1715492115
Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 115 (12)
Table of Contents

Submit

Sign up for Article Alerts

Article Classifications

  • Biological Sciences
  • Neuroscience

Jump to section

  • Article
    • Abstract
    • Results
    • Discussion
    • Materials and Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Abstract depiction of a guitar and musical note
Science & Culture: At the nexus of music and medicine, some see disease treatments
Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s.
Image credit: Shutterstock/agsandrew.
Large piece of gold
News Feature: Tracing gold's cosmic origins
Astronomers thought they’d finally figured out where gold and other heavy elements in the universe came from. In light of recent results, they’re not so sure.
Image credit: Science Source/Tom McHugh.
Dancers in red dresses
Journal Club: Friends appear to share patterns of brain activity
Researchers are still trying to understand what causes this strong correlation between neural and social networks.
Image credit: Shutterstock/Yeongsik Im.
White and blue bird
Hazards of ozone pollution to birds
Amanda Rodewald, Ivan Rudik, and Catherine Kling talk about the hazards of ozone pollution to birds.
Listen
Past PodcastsSubscribe
Goats standing in a pin
Transplantation of sperm-producing stem cells
CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds.
Image credit: Jon M. Oatley.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Librarians
  • Press
  • Site Map
  • PNAS Updates

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490