[article]
| Titre : |
Identification of amygdala-expressed genes associated with autism spectrum disorder |
| Type de document : |
texte imprimé |
| Auteurs : |
Maria Jesus HERRERO, Auteur ; Dmitry VELMESHEV, Auteur ; David HERNANDEZ-PINEDA, Auteur ; Saarthak SETHI, Auteur ; Shawn SORRELLS, Auteur ; Payal BANERJEE, Auteur ; Catherine SULLIVAN, Auteur ; Abha R. GUPTA, Auteur ; Arnold R. KRIEGSTEIN, Auteur ; Joshua G. CORBIN, Auteur |
| Article en page(s) : |
39 p. |
| Langues : |
Anglais (eng) |
| Mots-clés : |
ASD genes Amygdala Autism spectrum disorder Brain development Single nucleus RNA sequencing |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development. METHODS: Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20 years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD. RESULTS: Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline. LIMITATIONS: We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages. CONCLUSIONS: Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala. |
| En ligne : |
http://dx.doi.org/10.1186/s13229-020-00346-1 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 |
in Molecular Autism > 11 (2020) . - 39 p.
[article] Identification of amygdala-expressed genes associated with autism spectrum disorder [texte imprimé] / Maria Jesus HERRERO, Auteur ; Dmitry VELMESHEV, Auteur ; David HERNANDEZ-PINEDA, Auteur ; Saarthak SETHI, Auteur ; Shawn SORRELLS, Auteur ; Payal BANERJEE, Auteur ; Catherine SULLIVAN, Auteur ; Abha R. GUPTA, Auteur ; Arnold R. KRIEGSTEIN, Auteur ; Joshua G. CORBIN, Auteur . - 39 p. Langues : Anglais ( eng) in Molecular Autism > 11 (2020) . - 39 p.
| Mots-clés : |
ASD genes Amygdala Autism spectrum disorder Brain development Single nucleus RNA sequencing |
| Index. décimale : |
PER Périodiques |
| Résumé : |
BACKGROUND: Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development. METHODS: Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20 years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD. RESULTS: Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline. LIMITATIONS: We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages. CONCLUSIONS: Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala. |
| En ligne : |
http://dx.doi.org/10.1186/s13229-020-00346-1 |
| Permalink : |
https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 |
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