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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Kucera, Katerina S 
Vino, Arianna 
Asher, Julian E 
Baron-Cohen, Simon 

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.

Description

Keywords

axonogenesis, perception, synaesthesia, synesthesia, whole-exome sequencing, Auditory Perception, Axons, Collagen Type IV, Color Perception, Female, Gene Expression, Genetic Variation, Humans, Integrin alpha2, Intercellular Signaling Peptides and Proteins, Male, Myosins, Nerve Tissue Proteins, Pedigree, Perceptual Disorders, RGS Proteins, Receptors, Cell Surface, Receptors, Immunologic, Sodium-Hydrogen Exchangers, Synesthesia

Journal Title

Proc Natl Acad Sci U S A

Conference Name

Journal ISSN

0027-8424
1091-6490

Volume Title

115

Publisher

Proceedings of the National Academy of Sciences