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Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder / Lin WANG in Molecular Autism, 11 (2020)
[article]
Titre : Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : Lin WANG, Auteur ; Yi ZHANG, Auteur ; Kuokuo LI, Auteur ; Zheng WANG, Auteur ; Xiaomeng WANG, Auteur ; Bin LI, Auteur ; Guihu ZHAO, Auteur ; Zhenghuan FANG, Auteur ; Zhengbao LING, Auteur ; Tengfei LUO, Auteur ; Lu XIA, Auteur ; Yanping LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Jinchen LI, Auteur ; Zhongsheng SUN, Auteur ; Kun XIA, Auteur Article en page(s) : 75 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder De novo variant Expression pattern Functional network Recessive inherited variant Index. décimale : PER Périodiques Résumé : BACKGROUND: Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). METHODS: We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. RESULTS: Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p?=?0.038) and X-linked inherited PTVs in males (p?=?0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. LIMITATIONS: The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. CONCLUSIONS: ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs. En ligne : http://dx.doi.org/10.1186/s13229-020-00382-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433
in Molecular Autism > 11 (2020) . - 75 p.[article] Functional relationships between recessive inherited genes and genes with de novo variants in autism spectrum disorder [Texte imprimé et/ou numérique] / Lin WANG, Auteur ; Yi ZHANG, Auteur ; Kuokuo LI, Auteur ; Zheng WANG, Auteur ; Xiaomeng WANG, Auteur ; Bin LI, Auteur ; Guihu ZHAO, Auteur ; Zhenghuan FANG, Auteur ; Zhengbao LING, Auteur ; Tengfei LUO, Auteur ; Lu XIA, Auteur ; Yanping LI, Auteur ; Hui GUO, Auteur ; Zhengmao HU, Auteur ; Jinchen LI, Auteur ; Zhongsheng SUN, Auteur ; Kun XIA, Auteur . - 75 p.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020) . - 75 p.
Mots-clés : Autism spectrum disorder De novo variant Expression pattern Functional network Recessive inherited variant Index. décimale : PER Périodiques Résumé : BACKGROUND: Both de novo variants and recessive inherited variants were associated with autism spectrum disorder (ASD). This study aimed to use exome data to prioritize recessive inherited genes (RIGs) with biallelically inherited variants in autosomes or X-linked inherited variants in males and investigate the functional relationships between RIGs and genes with de novo variants (DNGs). METHODS: We used a bioinformatics pipeline to analyze whole-exome sequencing data from 1799 ASD quads (containing one proband, one unaffected sibling, and their parents) from the Simons Simplex Collection and prioritize candidate RIGs with rare biallelically inherited variants in autosomes or X-linked inherited variants in males. The relationships between RIGs and DNGs were characterized based on different genetic perspectives, including genetic variants, functional networks, and brain expression patterns. RESULTS: Among the biallelically or hemizygous constrained genes that were expressed in the brain, ASD probands carried significantly more biallelically inherited protein-truncating variants (PTVs) in autosomes (p?=?0.038) and X-linked inherited PTVs in males (p?=?0.026) than those in unaffected siblings. We prioritized eight autosomal, and 13 X-linked candidate RIGs, including 11 genes already associated with neurodevelopmental disorders. In total, we detected biallelically inherited variants or X-linked inherited variants of these 21 candidate RIGs in 26 (1.4%) of 1799 probands. We then integrated previously reported known or candidate genes in ASD, ultimately obtaining 70 RIGs and 87 DNGs for analysis. We found that RIGs were less likely to carry multiple recessive inherited variants than DNGs were to carry multiple de novo variants. Additionally, RIGs and DNGs were significantly co-expressed and interacted with each other, forming a network enriched in known functional ASD clusters, although RIGs were less likely to be enriched in these functional clusters compared with DNGs. Furthermore, although RIGs and DNGs presented comparable expression patterns in the human brain, RIGs were less likely to be associated with prenatal brain regions, the middle cortical layers, and excitatory neurons than DNGs. LIMITATIONS: The RIGs analyzed in this study require functional validation, and the results should be replicated in more patients with ASD. CONCLUSIONS: ASD RIGs were functionally associated with DNGs; however, they exhibited higher heterogeneity than DNGs. En ligne : http://dx.doi.org/10.1186/s13229-020-00382-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=433 Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders / K. LI in Journal of Autism and Developmental Disorders, 52-3 (March 2022)
[article]
Titre : Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders Type de document : Texte imprimé et/ou numérique Auteurs : K. LI, Auteur ; Z. FANG, Auteur ; G. ZHAO, Auteur ; B. LI, Auteur ; C. CHEN, Auteur ; L. XIA, Auteur ; L. WANG, Auteur ; T. LUO, Auteur ; X. WANG, Auteur ; Z. WANG, Auteur ; Y. ZHANG, Auteur ; Y. JIANG, Auteur ; Q. PAN, Auteur ; Z. HU, Auteur ; H. GUO, Auteur ; B. TANG, Auteur ; C. LIU, Auteur ; Z. SUN, Auteur ; K. XIA, Auteur ; J. LI, Auteur Article en page(s) : p.1299-1313 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/genetics Genetic Predisposition to Disease Humans Intellectual Disability/genetics Mutation Phenotype Schizophrenia Candidate gene De novo mutation Expression pattern Functional network Neuropsychiatric disorder Index. décimale : PER Périodiques Résumé : The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.11%, 34.40%, 33.31%, 10.98% and 6.91% of patients with ID, EE, UDD, ASD and SCZ, respectively. Consistent with phenotype similarity and heterogeneity in different NPDs, they show different degree of genetic association. Cross-disorder analysis of DNMs prioritized 321 candidate genes (FDR?0.05) and showed that genes shared in more disorders were more likely to exhibited specific expression pattern, functional pathway, genetic convergence, and genetic intolerance. En ligne : http://dx.doi.org/10.1007/s10803-021-05031-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455
in Journal of Autism and Developmental Disorders > 52-3 (March 2022) . - p.1299-1313[article] Cross-Disorder Analysis of De Novo Mutations in Neuropsychiatric Disorders [Texte imprimé et/ou numérique] / K. LI, Auteur ; Z. FANG, Auteur ; G. ZHAO, Auteur ; B. LI, Auteur ; C. CHEN, Auteur ; L. XIA, Auteur ; L. WANG, Auteur ; T. LUO, Auteur ; X. WANG, Auteur ; Z. WANG, Auteur ; Y. ZHANG, Auteur ; Y. JIANG, Auteur ; Q. PAN, Auteur ; Z. HU, Auteur ; H. GUO, Auteur ; B. TANG, Auteur ; C. LIU, Auteur ; Z. SUN, Auteur ; K. XIA, Auteur ; J. LI, Auteur . - p.1299-1313.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 52-3 (March 2022) . - p.1299-1313
Mots-clés : Autism Spectrum Disorder/genetics Genetic Predisposition to Disease Humans Intellectual Disability/genetics Mutation Phenotype Schizophrenia Candidate gene De novo mutation Expression pattern Functional network Neuropsychiatric disorder Index. décimale : PER Périodiques Résumé : The clinical similarity among different neuropsychiatric disorders (NPDs) suggested a shared genetic basis. We catalogued 23,109 coding de novo mutations (DNMs) from 6511 patients with autism spectrum disorder (ASD), 4,293 undiagnosed developmental disorder (UDD), 933 epileptic encephalopathy (EE), 1022 intellectual disability (ID), 1094 schizophrenia (SCZ), and 3391 controls. We evaluated that putative functional DNMs contribute to 38.11%, 34.40%, 33.31%, 10.98% and 6.91% of patients with ID, EE, UDD, ASD and SCZ, respectively. Consistent with phenotype similarity and heterogeneity in different NPDs, they show different degree of genetic association. Cross-disorder analysis of DNMs prioritized 321 candidate genes (FDR?0.05) and showed that genes shared in more disorders were more likely to exhibited specific expression pattern, functional pathway, genetic convergence, and genetic intolerance. En ligne : http://dx.doi.org/10.1007/s10803-021-05031-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455