Axonogenesis Gene Variants Linked To Sound–color Synesthesia

New genetic clues that could help explain the biology of synaesthesia are reported by scientists from the Max Planck Institute for Psycholinguistics and the University of Cambridge. The researchers carefully analysed the DNA of three families in which multiple members, across several different generations, experience colour when listening to sounds.

One in 25 people have synesthesia, in which an experience involving one sense is associated with perception in another sense — for example, seeing colors when listening to music.

Some people with synaesthesia may see sounds, while others may taste them or feel them as shapes. This kind of sensory cross-talk comes in many forms, and develops during early childhood. It has been known for over a century that synaesthesia runs in families, giving a strong hint that inherited factors are important.

Differently Wired

Dr. Amanda Tilot, a geneticist at the Max Planck Institute for Psycholinguistics, said;

“Brain imaging of adults with synaesthesia suggests that their circuits are wired a little differently compared to people who don’t make these extra sensory associations. What we don’t know yet is how these differences develop. We suspect some of the answers lie in people’s genetic makeup.”

The team took advantage of advances in genome sequencing, enabling them to identify genetic variants in the synaesthesia families and track how they were passed on from one generation to the next.

Six synesthesia candidate genes are widely expressed across neural development.

Six synesthesia candidate genes are widely expressed across neural development.
(A) Expression data from the ABA, mapped to a unified anatomic framework.
(B) Gene expression in human parietal, primary auditory, and primary visual cortices from 12 wk post conception to age 40 y, from the BrainSpan atlas (one to three independent measurements per gene, region, and time point); the y axis uses a log2 scale to visualize change over time for each gene.
(C) Neural gene expression in specific cell types isolated from adult mice. Boxes represent the 25th to 75th percentiles; whiskers extend to 1.5 times
Credit: Amanda K. Tilot el al., CC-BY

In particular, they focused attention on rare DNA changes that altered the way genes code for proteins, and that perfectly matched the inheritance of synaesthesia in each of the three families.

Axonogenesis

While the highlighted DNA variants differed between the three families, a common theme emerged to connect them: an enrichment for genes involved in axonogenesis and cell migration. Axonogenesis, the formation of new axons, is a key process enabling brain cells to wire up to their correct partners.

synesthesia in three multiplex families

Sound–color synesthesia in three multiplex families from the Cambridge Synaesthesia Research Group.
(A) Pedigrees of the families. Circles indicate females, squares refer to males, and gray shading indicates synesthesia. Blue outlines show which members underwent WES.
(B) An illustration of sound–color matching over three trials (colored boxes) for three hypothetical individuals presented with two auditory stimuli.
A synesthete (boxes on the left) would show high consistency across trials, while a nonsynesthete (boxes on the right) would be inconsistent in their color choices.
Credit: Amanda K. Tilot el al., CC-BY

Professor Simon Fisher, Director of the Max Planck Institute, who led the research, said,

“We knew from earlier studies by the Cambridge team that no single gene can account for this intriguing trait; even families who experience the same form of synaesthesia are likely to differ in terms of specific genetic explanations. Our hope was that the DNA data might point to shared biological processes as candidates for involvement in synaesthesia.”

Professor Simon Baron-Cohen, Director of the Autism Research Centre, Cambridge University, commented,

“This research is revealing how genetic variation can modify our sensory experiences, potentially via altered connectivity in the brain. Synaesthesia is a clear example of neurodiversity which we should respect and celebrate.”

To better understand these findings, the team is looking for new families and individuals to join their study. To learn more about their research and take a short test to find out if you experience a common form of synaesthesia, go to http://www.mpi.nl/synaesthesia.

Support for the work was provided by the European Commission, the Hertie Foundation through the Eric Kandel Young Neuroscientists Prize and by the Max Planck Society.

Amanda K. Tilot, Katerina S. Kucera, Arianna Vino, Julian E. Asher, Simon Baron-Cohen, Simon E. Fisher
Rare variants in axonogenesis genes connect three families with sound–color synesthesia
Proceedings of the National Academy of Sciences Mar 2018, 201715492; DOI: 10.1073/pnas.1715492115

Top Image: Dominik from Germany CC BY-SA 2.0, via Wikimedia Commons