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A Common CYFIP1 Variant at the 15q11.2 Disease Locus Is Associated with Structural Variation at the Language-Related Left Supramarginal Gyrus
- Source :
- PLoS One, 11, 6, PLoS One, 11, PLoS ONE, Vol 11, Iss 6, p e0158036 (2016), PLoS ONE, PLoS One
- Publication Year :
- 2016
-
Abstract
- s Metrics Comments Related Content Abstract Introduction Materials and Methods Results Discussion Supporting Information Acknowledgments Author Contributions References Reader Comments (0) Media Coverage Figures Abstract Copy number variants (CNVs) at the Breakpoint 1 to Breakpoint 2 region at 15q11.2 (BP1-2) are associated with language-related difficulties and increased risk for developmental disorders in which language is compromised. Towards underlying mechanisms, we investigated relationships between single nucleotide polymorphisms (SNPs) across the region and quantitative measures of human brain structure obtained by magnetic resonance imaging of healthy subjects. We report an association between rs4778298, a common variant at CYFIP1, and inter-individual variation in surface area across the left supramarginal gyrus (lh.SMG), a cortical structure implicated in speech and language in independent discovery (n = 100) and validation cohorts (n = 2621). In silico analyses determined that this same variant, and others nearby, is also associated with differences in levels of CYFIP1 mRNA in human brain. One of these nearby polymorphisms is predicted to disrupt a consensus binding site for FOXP2, a transcription factor implicated in speech and language. Consistent with a model where FOXP2 regulates CYFIP1 levels and in turn influences lh.SMG surface area, analysis of publically available expression data identified a relationship between expression of FOXP2 and CYFIP1 mRNA in human brain. We propose that altered CYFIP1 dosage, through aberrant patterning of the lh.SMG, may contribute to language-related difficulties associated with BP1-2 CNVs. More generally, this approach may be useful in clarifying the contribution of individual genes at CNV risk loci.
- Subjects :
- 0301 basic medicine
Heredity
Social Sciences
Gene Expression
lcsh:Medicine
Biochemistry
Diagnostic Radiology
0302 clinical medicine
Parietal Lobe
Medicine and Health Sciences
Psychology
Copy-number variation
lcsh:Science
Language
Genetics
Multidisciplinary
Radiology and Imaging
Forkhead Transcription Factors
FOXP2
Human brain
Magnetic Resonance Imaging
Genetic Mapping
medicine.anatomical_structure
Research Article
Neuroinformatics
DNA Copy Number Variations
Imaging Techniques
Variant Genotypes
Locus (genetics)
Single-nucleotide polymorphism
Biology
Research and Analysis Methods
Language Development
150 000 MR Techniques in Brain Function
Structural variation
03 medical and health sciences
Diagnostic Medicine
Mental Health and Psychiatry
DNA-binding proteins
medicine
Speech
Humans
Gene Regulation
Gene
Adaptor Proteins, Signal Transducing
Chromosomes, Human, Pair 15
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
Breakpoint
lcsh:R
Cognitive Psychology
Biology and Life Sciences
Proteins
Linguistics
Regulatory Proteins
030104 developmental biology
Genetic Loci
Case-Control Studies
Schizophrenia
Cognitive Science
lcsh:Q
030217 neurology & neurosurgery
Neuroscience
Transcription Factors
Subjects
Details
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS One, 11, 6, PLoS One, 11, PLoS ONE, Vol 11, Iss 6, p e0158036 (2016), PLoS ONE, PLoS One
- Accession number :
- edsair.doi.dedup.....9de509e6ce2856c23a5b1bd4e0433f32