In search of the genetic basis of the cerebral lateralization of language through an innovative alliance between functional imaging and full genome sequencing

For the vast majority of human beings, it is the left hemisphere of the brain that is dominant for various aspects of language processing. Only less than 1% of the adult population has an atypical inverted dominance of their right hemisphere for language (LDAtyp). This one could partly be of genetic origin.

The genetic program underlying left lateralization for language domainance is unknown, as are the causes of the very rare LDAtyp variation. Assuming that rare genetic mutations could be implicated in LDAtyp, a multidisciplinary consortium of researchers from Nijmegen (NL), Bordeaux (F) and Ghent (B) conducted an exploratory full-genome sequencing study in search of such mutations. Using databases specifically designed for the study of cerebral lateralisation (BIL&GIN, Bordeaux and GOAL, Ghent), this consortium was able to constitute a sample of 33 individuals with a confirmed LDAtyp using functional magnetic resonance imaging.

Top: Illustration of the typical left hemisphere dominance for language, observed by functional MRI in an individual during a silent sentence production task.
Bottom: Same for an individual with atypical dominance of the right hemisphere  while performing the same task.
(credits: BIL & GIN database, Neurofunctional Imaging Group, Institute of Neurodegenerative Diseases, CEA, CNRS, University of Bordeaux)

The full genome sequencing of these 33 individuals was performed and compared to that of a control sample from the same two databases, consisting of 34 individuals with typical left laterality for the language, as well as to a large ensemble of population genetic data (UK Biobank). The study revealed a significantly higher number of mutations in LDATyp individuals within a group of genes involved in the actin cytoskeleton, a key constituent of cell structure involved in the mechanisms of left-right axis setup in invertebrates. This study, which is the first to combine brain imaging and full genome sequencing, provides a preliminary overview of molecular genetic influences on hemispheric dominance for language.

Reference

Genome sequencing for rightward hemispheric language dominance. Carrion-Castillo A, L Van der Haegen L, Tzourio-Mazoyer N, Kavaklioglu T, Badillo S, Chavent M, Saracco J, Brysbaert M, Fisher SE, Mazoyer B, and Francks C. Genes, Brain and Behavior, manuscript number: G2B-00025-2019.R1, accepted for publication.

Contact: Bernard Mazoyer

Funding

This research was funded by the ANR (Contract No. 15-HBPR-0001-03) and the Netherlands Organization for Scientific Research (NWO Contract No. 054-15-101) as part of the ‘MULTI-LATERAL‘ consortium, a FLAG-ERA project partner of the EU Human Brain Project Flagship. Additional funding was obtained from the Max Planck Society (Germany) and IdEx Bordeaux (InterLabex 2013 program, ANR contract n ° 10-IDEX-03-02). The GOAL database was acquired through an Odysseus contract from the Government of Flanders. Genetic data from UK Biobank were obtained under Project No. 16066. The BIL & GIN database was funded by the Neurofunctional Imaging Group, CI-NAPS UMR6232, CEA, CNRS, University of Caen Basse-Normandie.