Journal article
The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language
Behavior genetics, Vol.42(4), pp.509-527
07/2012
DOI: 10.1007/s10519-012-9532-3
PMCID: PMC3375077
PMID: 22426781
Abstract
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.
Details
- Title: Subtitle
- The Aromatase Gene CYP19A1: Several Genetic and Functional Lines of Evidence Supporting a Role in Reading, Speech and Language
- Creators
- Heidi Anthoni - Department of Medical Genetics, Biomedicum, University of Helsinki, 00014 Helsinki, FinlandLara E Sucheston - Department of Biostatistics, State University of New York at Buffalo, Buffalo, NY 14214-3000 USABarbara A Lewis - Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH 44106 USAIsabel Tapia-Páez - Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, SwedenXiaotang Fan - Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, SwedenMarco Zucchelli - Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, SwedenMikko Taipale - Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142-1479 USACatherine M Stein - Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106 USAMarie-Estelle Hokkanen - Neuroscience Center, University of Helsinki, 00014 Helsinki, FinlandEero Castrén - Neuroscience Center, University of Helsinki, 00014 Helsinki, FinlandBruce F Pennington - Department of Psychology, University of Denver, Denver, CO 80208 USAShelley D Smith - Munroe Meyer Institute, University of Nebraska Medical Center, Omaha, NE 68198-5450 USARichard K Olson - Department of Psychology, University of Colorado, Boulder, CO USAJ. Bruce Tomblin - Department of Communication Sciences and Disorders, University of Iowa, Iowa City, IA 52242 USAGerd Schulte-Körne - Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Ludwig-Maximilians-University of Munich, 80336 Munich, GermanyMarkus Nöthen - Department of Genomics, Life and Brain Centre, University of Bonn, 53127 Bonn, GermanyJohannes Schumacher - Institute of Human Genetics, Biomedical Centre, University of Bonn, 53127 Bonn, GermanyBertram Müller-Myhsok - Max-Planck Institute of Psychiatry, 80804 Munich, GermanyPer Hoffmann - Department of Genomics, Life and Brain Centre, University of Bonn, 53127 Bonn, GermanyJeffrey W Gilger - Psychological Sciences, University of California, Merced, CA 95343 USAGeorge W Hynd - Department of Psychology, College of Charleston, 66 George Street, Charleston, SC 29424 USAJaana Nopola-Hemmi - Division of Child Neurology, Department of Gynecology and Pediatrics, HUCH, University of Helsinki, 00014 Helsinki, FinlandPaavo H. T Leppanen - Department of Psychology, University of Jyväskylä, 40014 Jyväskylä, FinlandHeikki Lyytinen - Department of Psychology, University of Jyväskylä, 40014 Jyväskylä, FinlandJacqueline Schoumans - Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital, 171 76 Stockholm, SwedenMagnus Nordenskjöld - Department of Molecular Medicine and Surgery, Karolinska Institutet at Karolinska University Hospital, 171 76 Stockholm, SwedenJason Spencer - Howard Florey Institute, Parkville, VIC 3010 AustraliaDavor Stanic - Howard Florey Institute, Parkville, VIC 3010 AustraliaWah Chin Boon - Howard Florey Institute, Parkville, VIC 3010 AustraliaEvan Simpson - Prince Henry’s Institute of Medical Research, Clayton, VIC 3168 AustraliaSari Mäkelä - Institute of Biomedicine, University of Turku, 20014 Turku, FinlandJan-Åke Gustafsson - Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, SwedenMyriam Peyrard-Janvid - Department of Biosciences and Nutrition, Karolinska Institutet, 141 83 Huddinge, SwedenSudha Iyengar - Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH 44106 USAJuha Kere - Department of Medical Genetics, Biomedicum, University of Helsinki, 00014 Helsinki, Finland
- Resource Type
- Journal article
- Publication Details
- Behavior genetics, Vol.42(4), pp.509-527
- DOI
- 10.1007/s10519-012-9532-3
- PMID
- 22426781
- PMCID
- PMC3375077
- NLM abbreviation
- Behav Genet
- ISSN
- 0001-8244
- eISSN
- 1573-3297
- Publisher
- Springer US; Boston
- Language
- English
- Date published
- 07/2012
- Academic Unit
- Communication Sciences and Disorders; Iowa Neuroscience Institute
- Record Identifier
- 9984070789702771
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