The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language
| Autor: | Isabel Tapia-Páez, J. Bruce Tomblin, Marco Zucchelli, Sudha K. Iyengar, Johannes Schumacher, Shelley D. Smith, Jaana Nopola-Hemmi, Markus M. Nöthen, Xiaotang Fan, Barbara A. Lewis, Jason Spencer, Bruce F. Pennington, Jeffrey W. Gilger, Per Hoffmann, Heidi Anthoni, Gerd Schulte-Körne, Catherine M. Stein, Davor Stanic, Sari Mäkelä, Marie-Estelle Hokkanen, Richard K. Olson, Evan R. Simpson, Mikko Taipale, George W. Hynd, Jan-Åke Gustafsson, Juha Kere, Heikki Lyytinen, Myriam Peyrard-Janvid, Wah Chin Boon, Bertram Müller-Myhsok, Eero Castrén, Jacqueline Schoumans, Magnus Nordenskjöld, Paavo H.T. Leppänen, Lara Sucheston |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Candidate gene SLI Estrogen synthesis Translocation Genetic Dyslexia Cohort Studies Mice 0302 clinical medicine Genetics(clinical) Receptors Immunologic Aromatase Promoter Regions Genetic Genetics (clinical) Original Research Quantitative trait analysis Mice Knockout Genetics Regulation of gene expression 0303 health sciences biology Brain Nuclear Proteins Human brain medicine.anatomical_structure Translocation breakpoint Female endocrine system medicine.drug_class Quantitative Trait Loci Nerve Tissue Proteins Polymorphism Single Nucleotide Speech Disorders 03 medical and health sciences ROBO1 medicine Animals Humans Genetic Predisposition to Disease RNA Messenger Ecology Evolution Behavior and Systematics SSD 030304 developmental biology Language Disorders Aromatase inhibitor Categorical trait association medicine.disease Cytoskeletal Proteins Gene Expression Regulation Synaptic plasticity biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Behavior Genetics |
| ISSN: | 1573-3297 0001-8244 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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