title: Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions.
abstract: Recent advances have been made in the genetics of two human communication skills: speaking and reading. Mutations of the FOXP2 gene cause a severe form of language impairment and orofacial dyspraxia, while single-nucleotide polymorphisms (SNPs) located within a KIAA0319/TTRAP/THEM2 gene cluster and affecting the KIAA0319 gene expression are associated with reading disability. Neuroimaging studies of clinical populations point to partially distinct cerebral bases for language and reading impairments. However, alteration of FOXP2 and KIAA0319/TTRAP/THEM2 polymorphisms on typically developed language networks has never been explored. Here, we genotyped and scanned 94 healthy subjects using fMRI during a reading task. We studied the correlation of genetic polymorphisms with interindividual variability in brain activation and functional asymmetry in frontal and temporal cortices. In FOXP2, SNPs rs6980093 and rs7799109 were associated with variations of activation in the left frontal cortex. In the KIAA0319/TTRAP/THEM2 locus, rs17243157 was associated with asymmetry in functional activation of the superior temporal sulcus (STS). Interestingly, healthy subjects bearing the KIAA0319/TTRAP/THEM2 variants previously identified as enhancing the risk of dyslexia showed a reduced left-hemispheric asymmetry of the STS. Our results confirm that both FOXP2 and KIAA0319/TTRAP/THEM2 genes play an important role in human language development, but probably through different cerebral pathways. The observed cortical effects mirror previous fMRI results in developmental language and reading disorders, and suggest that a continuum may exist between these pathologies and normal interindividual variability.
authors.affiliation: INSERM, U992, Cognitive Neuroimaging Unit, F-91191 Gif/Yvette, France. philippe.pinel@cea.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Pinel
authors.forename: Fabien
authors.initials: F
authors.lastname: Fauchereau
authors.forename: Antonio
authors.initials: A
authors.lastname: Moreno
authors.forename: Alexis
authors.initials: A
authors.lastname: Barbot
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Diana
authors.initials: D
authors.lastname: Zelenika
authors.forename: Denis
authors.initials: D
authors.lastname: Le Bihan
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Poline
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourgeron
authors.forename: Stanislas
authors.initials: S
authors.lastname: Dehaene
mesh_terms: D000328:Adult; D004268:DNA-Binding Proteins; D004410:Dyslexia / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005625:Frontal Lobe / Q000098:blood supply / Q000502:physiology*; D007839:Functional Laterality / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010100:Oxygen; D010727:Phosphoric Diester Hydrolases; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011932:Reading; D013702:Temporal Lobe / Q000098:blood supply / Q000502:physiology*; D013869:Thiolester Hydrolases / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; C500377:KIAA0319 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C514740:ACOT13 protein, human; D013869:Thiolester Hydrolases; D010727:Phosphoric Diester Hydrolases; C474866:TDP2 protein, human; D010100:Oxygen