Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development
Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and...
Ausführliche Beschreibung
Autor*in: |
Zhenwei Liu [verfasserIn] Na Zhang [verfasserIn] Yu Zhang [verfasserIn] Yaoqiang Du [verfasserIn] Tao Zhang [verfasserIn] Zhongshan Li [verfasserIn] Jinyu Wu [verfasserIn] Xiaobing Wang [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2018 |
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Übergeordnetes Werk: |
In: Frontiers in Genetics - Frontiers Media S.A., 2011, 9(2018) |
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Übergeordnetes Werk: |
volume:9 ; year:2018 |
Links: |
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DOI / URN: |
10.3389/fgene.2018.00349 |
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Katalog-ID: |
DOAJ044433387 |
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10.3389/fgene.2018.00349 doi (DE-627)DOAJ044433387 (DE-599)DOAJa8a81ddfa0354254ac35572e6a358484 DE-627 ger DE-627 rakwb eng QH426-470 Zhenwei Liu verfasserin aut Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and coding DNM data sets from multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show evolutionary constraint against functional genetic variation. Moreover, these ID risk genes were preferentially expressed in the cortical regions from the early fetal to late mid-fetal stages. In particular, a genome-wide weighted co-expression network analysis suggested that ID genes tightly converge onto two biological modules (M1 and M2) during human brain development. Functional annotations showed specific enrichment of chromatin modification and transcriptional regulation for M1 and synaptic function for M2, implying the divergent etiology of the two modules. In addition, we curated 12 additional strong ID risk genes whose molecular interconnectivity with known ID genes (q-values < 0.3) was greater than random. These findings further highlight the biological convergence of ID risk genes and help improve our understanding of the genetic architecture of ID. intellectual disability de novo mutations brain development gene prioritization molecular convergence Genetics Na Zhang verfasserin aut Yu Zhang verfasserin aut Yaoqiang Du verfasserin aut Tao Zhang verfasserin aut Zhongshan Li verfasserin aut Jinyu Wu verfasserin aut Xiaobing Wang verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 9(2018) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:9 year:2018 https://doi.org/10.3389/fgene.2018.00349 kostenfrei https://doaj.org/article/a8a81ddfa0354254ac35572e6a358484 kostenfrei https://www.frontiersin.org/article/10.3389/fgene.2018.00349/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_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 9 2018 |
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10.3389/fgene.2018.00349 doi (DE-627)DOAJ044433387 (DE-599)DOAJa8a81ddfa0354254ac35572e6a358484 DE-627 ger DE-627 rakwb eng QH426-470 Zhenwei Liu verfasserin aut Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and coding DNM data sets from multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show evolutionary constraint against functional genetic variation. Moreover, these ID risk genes were preferentially expressed in the cortical regions from the early fetal to late mid-fetal stages. In particular, a genome-wide weighted co-expression network analysis suggested that ID genes tightly converge onto two biological modules (M1 and M2) during human brain development. Functional annotations showed specific enrichment of chromatin modification and transcriptional regulation for M1 and synaptic function for M2, implying the divergent etiology of the two modules. In addition, we curated 12 additional strong ID risk genes whose molecular interconnectivity with known ID genes (q-values < 0.3) was greater than random. These findings further highlight the biological convergence of ID risk genes and help improve our understanding of the genetic architecture of ID. intellectual disability de novo mutations brain development gene prioritization molecular convergence Genetics Na Zhang verfasserin aut Yu Zhang verfasserin aut Yaoqiang Du verfasserin aut Tao Zhang verfasserin aut Zhongshan Li verfasserin aut Jinyu Wu verfasserin aut Xiaobing Wang verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 9(2018) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:9 year:2018 https://doi.org/10.3389/fgene.2018.00349 kostenfrei https://doaj.org/article/a8a81ddfa0354254ac35572e6a358484 kostenfrei https://www.frontiersin.org/article/10.3389/fgene.2018.00349/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_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 9 2018 |
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10.3389/fgene.2018.00349 doi (DE-627)DOAJ044433387 (DE-599)DOAJa8a81ddfa0354254ac35572e6a358484 DE-627 ger DE-627 rakwb eng QH426-470 Zhenwei Liu verfasserin aut Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and coding DNM data sets from multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show evolutionary constraint against functional genetic variation. Moreover, these ID risk genes were preferentially expressed in the cortical regions from the early fetal to late mid-fetal stages. In particular, a genome-wide weighted co-expression network analysis suggested that ID genes tightly converge onto two biological modules (M1 and M2) during human brain development. Functional annotations showed specific enrichment of chromatin modification and transcriptional regulation for M1 and synaptic function for M2, implying the divergent etiology of the two modules. In addition, we curated 12 additional strong ID risk genes whose molecular interconnectivity with known ID genes (q-values < 0.3) was greater than random. These findings further highlight the biological convergence of ID risk genes and help improve our understanding of the genetic architecture of ID. intellectual disability de novo mutations brain development gene prioritization molecular convergence Genetics Na Zhang verfasserin aut Yu Zhang verfasserin aut Yaoqiang Du verfasserin aut Tao Zhang verfasserin aut Zhongshan Li verfasserin aut Jinyu Wu verfasserin aut Xiaobing Wang verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 9(2018) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:9 year:2018 https://doi.org/10.3389/fgene.2018.00349 kostenfrei https://doaj.org/article/a8a81ddfa0354254ac35572e6a358484 kostenfrei https://www.frontiersin.org/article/10.3389/fgene.2018.00349/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_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 9 2018 |
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10.3389/fgene.2018.00349 doi (DE-627)DOAJ044433387 (DE-599)DOAJa8a81ddfa0354254ac35572e6a358484 DE-627 ger DE-627 rakwb eng QH426-470 Zhenwei Liu verfasserin aut Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and coding DNM data sets from multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show evolutionary constraint against functional genetic variation. Moreover, these ID risk genes were preferentially expressed in the cortical regions from the early fetal to late mid-fetal stages. In particular, a genome-wide weighted co-expression network analysis suggested that ID genes tightly converge onto two biological modules (M1 and M2) during human brain development. Functional annotations showed specific enrichment of chromatin modification and transcriptional regulation for M1 and synaptic function for M2, implying the divergent etiology of the two modules. In addition, we curated 12 additional strong ID risk genes whose molecular interconnectivity with known ID genes (q-values < 0.3) was greater than random. These findings further highlight the biological convergence of ID risk genes and help improve our understanding of the genetic architecture of ID. intellectual disability de novo mutations brain development gene prioritization molecular convergence Genetics Na Zhang verfasserin aut Yu Zhang verfasserin aut Yaoqiang Du verfasserin aut Tao Zhang verfasserin aut Zhongshan Li verfasserin aut Jinyu Wu verfasserin aut Xiaobing Wang verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 9(2018) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:9 year:2018 https://doi.org/10.3389/fgene.2018.00349 kostenfrei https://doaj.org/article/a8a81ddfa0354254ac35572e6a358484 kostenfrei https://www.frontiersin.org/article/10.3389/fgene.2018.00349/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_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 9 2018 |
allfieldsSound |
10.3389/fgene.2018.00349 doi (DE-627)DOAJ044433387 (DE-599)DOAJa8a81ddfa0354254ac35572e6a358484 DE-627 ger DE-627 rakwb eng QH426-470 Zhenwei Liu verfasserin aut Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and coding DNM data sets from multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show evolutionary constraint against functional genetic variation. Moreover, these ID risk genes were preferentially expressed in the cortical regions from the early fetal to late mid-fetal stages. In particular, a genome-wide weighted co-expression network analysis suggested that ID genes tightly converge onto two biological modules (M1 and M2) during human brain development. Functional annotations showed specific enrichment of chromatin modification and transcriptional regulation for M1 and synaptic function for M2, implying the divergent etiology of the two modules. In addition, we curated 12 additional strong ID risk genes whose molecular interconnectivity with known ID genes (q-values < 0.3) was greater than random. These findings further highlight the biological convergence of ID risk genes and help improve our understanding of the genetic architecture of ID. intellectual disability de novo mutations brain development gene prioritization molecular convergence Genetics Na Zhang verfasserin aut Yu Zhang verfasserin aut Yaoqiang Du verfasserin aut Tao Zhang verfasserin aut Zhongshan Li verfasserin aut Jinyu Wu verfasserin aut Xiaobing Wang verfasserin aut In Frontiers in Genetics Frontiers Media S.A., 2011 9(2018) (DE-627)65799829X (DE-600)2606823-0 16648021 nnns volume:9 year:2018 https://doi.org/10.3389/fgene.2018.00349 kostenfrei https://doaj.org/article/a8a81ddfa0354254ac35572e6a358484 kostenfrei https://www.frontiersin.org/article/10.3389/fgene.2018.00349/full kostenfrei https://doaj.org/toc/1664-8021 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_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_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 9 2018 |
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Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development |
abstract |
Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and coding DNM data sets from multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show evolutionary constraint against functional genetic variation. Moreover, these ID risk genes were preferentially expressed in the cortical regions from the early fetal to late mid-fetal stages. In particular, a genome-wide weighted co-expression network analysis suggested that ID genes tightly converge onto two biological modules (M1 and M2) during human brain development. Functional annotations showed specific enrichment of chromatin modification and transcriptional regulation for M1 and synaptic function for M2, implying the divergent etiology of the two modules. In addition, we curated 12 additional strong ID risk genes whose molecular interconnectivity with known ID genes (q-values < 0.3) was greater than random. These findings further highlight the biological convergence of ID risk genes and help improve our understanding of the genetic architecture of ID. |
abstractGer |
Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and coding DNM data sets from multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show evolutionary constraint against functional genetic variation. Moreover, these ID risk genes were preferentially expressed in the cortical regions from the early fetal to late mid-fetal stages. In particular, a genome-wide weighted co-expression network analysis suggested that ID genes tightly converge onto two biological modules (M1 and M2) during human brain development. Functional annotations showed specific enrichment of chromatin modification and transcriptional regulation for M1 and synaptic function for M2, implying the divergent etiology of the two modules. In addition, we curated 12 additional strong ID risk genes whose molecular interconnectivity with known ID genes (q-values < 0.3) was greater than random. These findings further highlight the biological convergence of ID risk genes and help improve our understanding of the genetic architecture of ID. |
abstract_unstemmed |
Dissecting the genetic susceptibility to intellectual disability (ID) based on de novo mutations (DNMs) will aid our understanding of the neurobiological and genetic basis of ID. In this study, we identify 63 high-confidence ID genes with q-values < 0.1 based on four background DNM rates and coding DNM data sets from multiple sequencing cohorts. Bioinformatic annotations revealed a higher burden of these 63 ID genes in FMRP targets and CHD8 targets, and these genes show evolutionary constraint against functional genetic variation. Moreover, these ID risk genes were preferentially expressed in the cortical regions from the early fetal to late mid-fetal stages. In particular, a genome-wide weighted co-expression network analysis suggested that ID genes tightly converge onto two biological modules (M1 and M2) during human brain development. Functional annotations showed specific enrichment of chromatin modification and transcriptional regulation for M1 and synaptic function for M2, implying the divergent etiology of the two modules. In addition, we curated 12 additional strong ID risk genes whose molecular interconnectivity with known ID genes (q-values < 0.3) was greater than random. These findings further highlight the biological convergence of ID risk genes and help improve our understanding of the genetic architecture of ID. |
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Prioritized High-Confidence Risk Genes for Intellectual Disability Reveal Molecular Convergence During Brain Development |
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