Identification of Phonology-Related Genes and Functional Characterization of Broca’s and Wernicke’s Regions in Language and Learning Disorders
Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeki...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Nina Unger [verfasserIn] Stefan Heim [verfasserIn] Dominique I. Hilger [verfasserIn] Sebastian Bludau [verfasserIn] Peter Pieperhoff [verfasserIn] Sven Cichon [verfasserIn] Katrin Amunts [verfasserIn] Thomas W. Mühleisen [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Frontiers in Neuroscience - Frontiers Media S.A., 2008, 15(2021) |
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| Übergeordnetes Werk: |
volume:15 ; year:2021 |
| Links: |
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| DOI / URN: |
10.3389/fnins.2021.680762 |
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| 520 | |a Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. | ||
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10.3389/fnins.2021.680762 doi (DE-627)DOAJ062308424 (DE-599)DOAJ45974c8127704ccaad08d8ce5e891135 DE-627 ger DE-627 rakwb eng RC321-571 Nina Unger verfasserin aut Identification of Phonology-Related Genes and Functional Characterization of Broca’s and Wernicke’s Regions in Language and Learning Disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. development phonology gene expression Broca’s area Wernicke’s area Neurosciences. Biological psychiatry. Neuropsychiatry Nina Unger verfasserin aut Nina Unger verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Dominique I. Hilger verfasserin aut Sebastian Bludau verfasserin aut Peter Pieperhoff verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 15(2021) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:15 year:2021 https://doi.org/10.3389/fnins.2021.680762 kostenfrei https://doaj.org/article/45974c8127704ccaad08d8ce5e891135 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2021.680762/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 |
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10.3389/fnins.2021.680762 doi (DE-627)DOAJ062308424 (DE-599)DOAJ45974c8127704ccaad08d8ce5e891135 DE-627 ger DE-627 rakwb eng RC321-571 Nina Unger verfasserin aut Identification of Phonology-Related Genes and Functional Characterization of Broca’s and Wernicke’s Regions in Language and Learning Disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. development phonology gene expression Broca’s area Wernicke’s area Neurosciences. Biological psychiatry. Neuropsychiatry Nina Unger verfasserin aut Nina Unger verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Dominique I. Hilger verfasserin aut Sebastian Bludau verfasserin aut Peter Pieperhoff verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 15(2021) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:15 year:2021 https://doi.org/10.3389/fnins.2021.680762 kostenfrei https://doaj.org/article/45974c8127704ccaad08d8ce5e891135 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2021.680762/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 |
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10.3389/fnins.2021.680762 doi (DE-627)DOAJ062308424 (DE-599)DOAJ45974c8127704ccaad08d8ce5e891135 DE-627 ger DE-627 rakwb eng RC321-571 Nina Unger verfasserin aut Identification of Phonology-Related Genes and Functional Characterization of Broca’s and Wernicke’s Regions in Language and Learning Disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. development phonology gene expression Broca’s area Wernicke’s area Neurosciences. Biological psychiatry. Neuropsychiatry Nina Unger verfasserin aut Nina Unger verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Dominique I. Hilger verfasserin aut Sebastian Bludau verfasserin aut Peter Pieperhoff verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 15(2021) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:15 year:2021 https://doi.org/10.3389/fnins.2021.680762 kostenfrei https://doaj.org/article/45974c8127704ccaad08d8ce5e891135 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2021.680762/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 |
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10.3389/fnins.2021.680762 doi (DE-627)DOAJ062308424 (DE-599)DOAJ45974c8127704ccaad08d8ce5e891135 DE-627 ger DE-627 rakwb eng RC321-571 Nina Unger verfasserin aut Identification of Phonology-Related Genes and Functional Characterization of Broca’s and Wernicke’s Regions in Language and Learning Disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. development phonology gene expression Broca’s area Wernicke’s area Neurosciences. Biological psychiatry. Neuropsychiatry Nina Unger verfasserin aut Nina Unger verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Dominique I. Hilger verfasserin aut Sebastian Bludau verfasserin aut Peter Pieperhoff verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 15(2021) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:15 year:2021 https://doi.org/10.3389/fnins.2021.680762 kostenfrei https://doaj.org/article/45974c8127704ccaad08d8ce5e891135 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2021.680762/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 |
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10.3389/fnins.2021.680762 doi (DE-627)DOAJ062308424 (DE-599)DOAJ45974c8127704ccaad08d8ce5e891135 DE-627 ger DE-627 rakwb eng RC321-571 Nina Unger verfasserin aut Identification of Phonology-Related Genes and Functional Characterization of Broca’s and Wernicke’s Regions in Language and Learning Disorders 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. development phonology gene expression Broca’s area Wernicke’s area Neurosciences. Biological psychiatry. Neuropsychiatry Nina Unger verfasserin aut Nina Unger verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Stefan Heim verfasserin aut Dominique I. Hilger verfasserin aut Sebastian Bludau verfasserin aut Peter Pieperhoff verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Sven Cichon verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Katrin Amunts verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut Thomas W. Mühleisen verfasserin aut In Frontiers in Neuroscience Frontiers Media S.A., 2008 15(2021) (DE-627)55908109X (DE-600)2411902-7 1662453X nnns volume:15 year:2021 https://doi.org/10.3389/fnins.2021.680762 kostenfrei https://doaj.org/article/45974c8127704ccaad08d8ce5e891135 kostenfrei https://www.frontiersin.org/articles/10.3389/fnins.2021.680762/full kostenfrei https://doaj.org/toc/1662-453X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 15 2021 |
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identification of phonology-related genes and functional characterization of broca’s and wernicke’s regions in language and learning disorders |
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Identification of Phonology-Related Genes and Functional Characterization of Broca’s and Wernicke’s Regions in Language and Learning Disorders |
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Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. |
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Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. |
| abstract_unstemmed |
Impaired phonological processing is a leading symptom of multifactorial language and learning disorders suggesting a common biological basis. Here we evaluated studies of dyslexia, dyscalculia, specific language impairment (SLI), and the logopenic variant of primary progressive aphasia (lvPPA) seeking for shared risk genes in Broca’s and Wernicke’s regions, being key for phonological processing within the complex language network. The identified “phonology-related genes” from literature were functionally characterized using Atlas-based expression mapping (JuGEx) and gene set enrichment. Out of 643 publications from the last decade until now, we extracted 21 candidate genes of which 13 overlapped with dyslexia and SLI, six with dyslexia and dyscalculia, and two with dyslexia, dyscalculia, and SLI. No overlap was observed between the childhood disorders and the late-onset lvPPA often showing symptoms of learning disorders earlier in life. Multiple genes were enriched in Gene Ontology terms of the topics learning (CNTNAP2, CYFIP1, DCDC2, DNAAF4, FOXP2) and neuronal development (CCDC136, CNTNAP2, CYFIP1, DCDC2, KIAA0319, RBFOX2, ROBO1). Twelve genes showed above-average expression across both regions indicating moderate-to-high gene activity in the investigated cortical part of the language network. Of these, three genes were differentially expressed suggesting potential regional specializations: ATP2C2 was upregulated in Broca’s region, while DNAAF4 and FOXP2 were upregulated in Wernicke’s region. ATP2C2 encodes a magnesium-dependent calcium transporter which fits with reports about disturbed calcium and magnesium levels for dyslexia and other communication disorders. DNAAF4 (formerly known as DYX1C1) is involved in neuronal migration supporting the hypothesis of disturbed migration in dyslexia. FOXP2 is a transcription factor that regulates a number of genes involved in development of speech and language. Overall, our interdisciplinary and multi-tiered approach provided evidence that genetic and transcriptional variation of ATP2C2, DNAAF4, and FOXP2 may play a role in physiological and pathological aspects of phonological processing. |
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