6533b834fe1ef96bd129d77c
RESEARCH PRODUCT
The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language
Isabel Tapia-páezJ. Bruce TomblinMarco ZucchelliSudha K. IyengarJohannes SchumacherShelley D. SmithJaana Nopola-hemmiMarkus M. NöthenXiaotang FanBarbara A. LewisJason SpencerJason SpencerBruce F. PenningtonJeffrey W. GilgerPer HoffmannHeidi AnthoniGerd Schulte-körneCatherine M. SteinDavor StanicDavor StanicSari MäkeläMarie-estelle HokkanenRichard K. OlsonEvan R. SimpsonMikko TaipaleGeorge W. HyndJan-åke GustafssonJan-åke GustafssonJuha KereJuha KereHeikki LyytinenMyriam Peyrard-janvidWah Chin BoonBertram Müller-myhsokEero CastrénJacqueline SchoumansMagnus NordenskjöldPaavo H.t. LeppänenLara Suchestonsubject
MaleCandidate geneSLIEstrogen synthesisTranslocation GeneticDyslexiaCohort StudiesMice0302 clinical medicineGenetics(clinical)Receptors ImmunologicAromatasePromoter Regions GeneticGenetics (clinical)Original ResearchQuantitative trait analysisMice KnockoutGeneticsRegulation of gene expression0303 health sciencesbiologyBrainNuclear ProteinsHuman brainmedicine.anatomical_structureTranslocation breakpointFemaleendocrine systemmedicine.drug_classQuantitative Trait LociNerve Tissue ProteinsPolymorphism Single NucleotideSpeech Disorders03 medical and health sciencesAromataseROBO1GeneticsmedicineAnimalsHumansGenetic Predisposition to DiseaseRNA MessengerEcology Evolution Behavior and SystematicsSSD030304 developmental biologyLanguage DisordersAromatase inhibitorCategorical trait associationDyslexiamedicine.diseaseCytoskeletal ProteinsGene Expression RegulationSynaptic plasticitybiology.protein030217 neurology & neurosurgerydescription
Inspired by the localization, on 15q21.2 of the CYP19A1 gene in the linkage region of speech and language disorders, and a rare translocation in a dyslexic individual that was brought to our attention, we conducted a series of studies on the properties of CYP19A1 as a candidate gene for dyslexia and related conditions. The aromatase enzyme is a member of the cytochrome P450 super family, and it serves several key functions: it catalyzes the conversion of androgens into estrogens; during early mammalian development it controls the differentiation of specific brain areas (e.g. local estrogen synthesis in the hippocampus regulates synaptic plasticity and axonal growth); it is involved in sexual differentiation of the brain; and in songbirds and teleost fishes, it regulates vocalization. Our results suggest that variations in CYP19A1 are associated with dyslexia as a categorical trait and with quantitative measures of language and speech, such as reading, vocabulary, phonological processing and oral motor skills. Variations near the vicinity of its brain promoter region altered transcription factor binding, suggesting a regulatory role in CYP19A1 expression. CYP19A1 expression in human brain correlated with the expression of dyslexia susceptibility genes such as DYX1C1 and ROBO1. Aromatase-deficient mice displayed increased cortical neuronal density and occasional cortical heterotopias, also observed in Robo1−/− mice and human dyslexic brains, respectively. An aromatase inhibitor reduced dendritic growth in cultured rat neurons. From this broad set of evidence, we propose CYP19A1 as a candidate gene for human cognitive functions implicated in reading, speech and language. Electronic supplementary material The online version of this article (doi:10.1007/s10519-012-9532-3) contains supplementary material, which is available to authorized users.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-03-17 | Behavior Genetics |