---
_id: '11160'
abstract:
- lang: eng
text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent
cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses
macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency
affects neurodevelopmental is unclear. Here, employing human cerebral organoids,
we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories
with an accelerated and delayed generation of, respectively, inhibitory and excitatory
neurons that yields, at days 60 and 120, symmetrically opposite expansions in
their proportions. This imbalance is consistent with an enlargement of cerebral
organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic
design of patient-specific mutations and mosaic organoids, we define genotype-phenotype
relationships and uncover their cell-autonomous nature. Our results define cell-type-specific
CHD8-dependent molecular defects related to an abnormal program of proliferation
and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations,
our study uncovers reproducible developmental alterations that may be employed
for neurodevelopmental disease modeling.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Farnaz Freeman for technical assistance. This research was
supported by the Scientific Service Units (SSU) of IST Austria through resources
provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This
work supported by the European Union’s Horizon 2020 research and innovation program
(ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs);
the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele;
and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures
were created using BioRender.com.
article_number: '110615'
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlo Emanuele
full_name: Villa, Carlo Emanuele
last_name: Villa
- first_name: Cristina
full_name: Cheroni, Cristina
last_name: Cheroni
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Alejandro
full_name: López-Tóbon, Alejandro
last_name: López-Tóbon
- first_name: Bárbara
full_name: Oliveira, Bárbara
id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
last_name: Oliveira
- first_name: Roberto
full_name: Sacco, Roberto
id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
last_name: Sacco
- first_name: Aysan Çerağ
full_name: Yahya, Aysan Çerağ
id: 365A65F8-F248-11E8-B48F-1D18A9856A87
last_name: Yahya
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Michele
full_name: Gabriele, Michele
last_name: Gabriele
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Mariano
full_name: Gabitto, Mariano
last_name: Gabitto
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Giuseppe
full_name: Testa, Giuseppe
last_name: Testa
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism
to transient alterations in excitatory and inhibitory trajectories. Cell Reports.
2022;39(1). doi:10.1016/j.celrep.2022.110615
apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco,
R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615
chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon,
Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency
Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.”
Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615.
ieee: C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient
alterations in excitatory and inhibitory trajectories,” Cell Reports, vol.
39, no. 1. Elsevier, 2022.
ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ,
Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG,
Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations
in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.
mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient
Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol.
39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.
short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco,
A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer,
M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2024-03-25T23:30:25Z
day: '05'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
ec_funded: 1
external_id:
isi:
- '000785983900003'
pmid:
- '35385734'
file:
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keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I04205
name: Identification of converging Molecular Pathways Across Chromatinopathies as
Targets for Therapy
publication: Cell Reports
publication_identifier:
issn:
- 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
record:
- id: '12364'
relation: dissertation_contains
status: public
status: public
title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
and inhibitory trajectories
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 39
year: '2022'
...
---
_id: '12364'
abstract:
- lang: eng
text: "Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders
character\x02ized by behavioral symptoms such as problems in social communication
and interaction, as\r\nwell as repetitive, restricted behaviors and interests.
These disorders show a high degree\r\nof heritability and hundreds of risk genes
have been identifed using high throughput\r\nsequencing technologies. This genetic
heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD
but at the same time given rise to the concept of convergent\r\nmechanisms. Previous
studies have identifed that risk genes for ASD broadly converge\r\nonto specifc
functional categories with transcriptional regulation being one of the biggest\r\ngroups.
In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences
of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations
in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations
of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult
animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel
by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe
link the regulatory function of Setd5 to its interaction with the Paf1 and the
NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene
CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental
trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing.
While the former\r\nwere generated earlier in CHD8+/- organoids, the generation
of the latter was shifted to\r\nlater times in favor of a prolonged progenitor
expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling
heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B,
KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory
convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory
neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral
ganglionic eminence. As this project is still ongoing at the time of writing,
future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying
this shift with\r\nthe aim of linking these three ASD risk genes through biological
convergence."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
citation:
ama: Dotter C. Transcriptional consequences of mutations in genes associated with
Autism Spectrum Disorder. 2022. doi:10.15479/at:ista:12094
apa: Dotter, C. (2022). Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria.
https://doi.org/10.15479/at:ista:12094
chicago: Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes
Associated with Autism Spectrum Disorder.” Institute of Science and Technology
Austria, 2022. https://doi.org/10.15479/at:ista:12094.
ieee: C. Dotter, “Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022.
ista: Dotter C. 2022. Transcriptional consequences of mutations in genes associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria.
mla: Dotter, Christoph. Transcriptional Consequences of Mutations in Genes Associated
with Autism Spectrum Disorder. Institute of Science and Technology Austria,
2022, doi:10.15479/at:ista:12094.
short: C. Dotter, Transcriptional Consequences of Mutations in Genes Associated
with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.
date_created: 2023-01-24T13:09:57Z
date_published: 2022-09-19T00:00:00Z
date_updated: 2023-11-16T13:10:22Z
day: '19'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: GaNo
doi: 10.15479/at:ista:12094
ec_funded: 1
file:
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content_type: application/pdf
creator: cchlebak
date_created: 2023-01-24T13:15:45Z
date_updated: 2023-09-20T22:30:03Z
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language:
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month: '09'
oa: 1
oa_version: Published Version
page: '152'
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
grant_number: '401299'
name: Probing development and reversibility of autism spectrum disorders
- _id: 9B91375C-BA93-11EA-9121-9846C619BF3A
grant_number: '707964'
name: Critical windows and reversibility of ASD associated with mutations in chromatin
remodelers
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I04205
name: Identification of converging Molecular Pathways Across Chromatinopathies as
Targets for Therapy
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '3'
relation: part_of_dissertation
status: public
- id: '11160'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
title: Transcriptional consequences of mutations in genes associated with Autism Spectrum
Disorder
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2022'
...
---
_id: '9429'
abstract:
- lang: eng
text: De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3
lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency
leads to motor coordination deficits as well as ASD-relevant social and cognitive
impairments. However, induction of Cul3 haploinsufficiency later in life does
not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during
a critical developmental window. Here we show that Cul3 is essential to regulate
neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice
display cortical lamination abnormalities. At the molecular level, we found that
Cul3 controls neuronal migration by tightly regulating the amount of Plastin3
(Pls3), a previously unrecognized player of neural migration. Furthermore, we
found that Pls3 cell-autonomously regulates cell migration by regulating actin
cytoskeleton organization, and its levels are inversely proportional to neural
migration speed. Finally, we provide evidence that cellular phenotypes associated
with autism-linked gene haploinsufficiency can be rescued by transcriptional activation
of the intact allele in vitro, offering a proof of concept for a potential therapeutic
approach for ASDs.
acknowledged_ssus:
- _id: PreCl
acknowledgement: We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A.
Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the
management of our animal colony, as well as M. Schunn and the Preclinical Facility
team for technical assistance. We thank K. Heesom and her team at the University
of Bristol Proteomics Facility for the proteomics sample preparation, data generation,
and analysis support. We thank Y. B. Simon for kindly providing the plasmid for
lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration
and the fruitful discussions. This work was supported by the ISTPlus postdoctoral
fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon
2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by
the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D
(I3600-B27).
article_number: '3058'
article_processing_charge: No
article_type: original
author:
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Lena A
full_name: Schwarz, Lena A
id: 29A8453C-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Bernadette
full_name: Basilico, Bernadette
id: 36035796-5ACA-11E9-A75E-7AF2E5697425
last_name: Basilico
orcid: 0000-0003-1843-3173
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Georgi A
full_name: Dimchev, Georgi A
id: 38C393BE-F248-11E8-B48F-1D18A9856A87
last_name: Dimchev
orcid: 0000-0001-8370-6161
- first_name: Armel
full_name: Nicolas, Armel
id: 2A103192-F248-11E8-B48F-1D18A9856A87
last_name: Nicolas
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Caroline
full_name: Kreuzinger, Caroline
id: 382077BA-F248-11E8-B48F-1D18A9856A87
last_name: Kreuzinger
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Lisa
full_name: Knaus, Lisa
id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87
last_name: Knaus
- first_name: Zoe
full_name: Dobler, Zoe
id: D23090A2-9057-11EA-883A-A8396FC7A38F
last_name: Dobler
- first_name: Emanuele
full_name: Cacci, Emanuele
last_name: Cacci
- first_name: Florian KM
full_name: Schur, Florian KM
id: 48AD8942-F248-11E8-B48F-1D18A9856A87
last_name: Schur
orcid: 0000-0003-4790-8078
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein
homeostasis and cell migration during a critical window of brain development.
Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x
apa: Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A.,
Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-021-23123-x
chicago: Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan,
Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton
Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.”
Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.
ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis
and cell migration during a critical window of brain development,” Nature Communications,
vol. 12, no. 1. Springer Nature, 2021.
ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer
CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino
G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during
a critical window of brain development. Nature Communications. 12(1), 3058.
mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis
and Cell Migration during a Critical Window of Brain Development.” Nature Communications,
vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.
short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas,
C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur,
J.G. Danzl, G. Novarino, Nature Communications 12 (2021).
date_created: 2021-05-28T11:49:46Z
date_published: 2021-05-24T00:00:00Z
date_updated: 2024-09-10T12:04:26Z
day: '24'
ddc:
- '572'
department:
- _id: GaNo
- _id: JoDa
- _id: FlSc
- _id: MiSi
- _id: LifeSc
- _id: Bio
doi: 10.1038/s41467-021-23123-x
ec_funded: 1
external_id:
isi:
- '000658769900010'
file:
- access_level: open_access
checksum: 337e0f7959c35ec959984cacdcb472ba
content_type: application/pdf
creator: kschuh
date_created: 2021-05-28T12:39:43Z
date_updated: 2021-05-28T12:39:43Z
file_id: '9430'
file_name: 2021_NatureCommunications_Morandell.pdf
file_size: 9358599
relation: main_file
success: 1
file_date_updated: 2021-05-28T12:39:43Z
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 05A0D778-7A3F-11EA-A408-12923DDC885E
grant_number: F07807
name: Neural stem cells in autism and epilepsy
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: press_release
url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/
record:
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relation: earlier_version
status: public
- id: '12401'
relation: dissertation_contains
status: public
status: public
title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a
critical window of brain development
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 12
year: '2021'
...
---
_id: '6074'
abstract:
- lang: eng
text: "This dataset contains the supplementary data for the research paper \"Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition\".\r\n\r\nThe contained files have the following content:\r\n'Supplementary
Figures.pdf'\r\n\tAdditional figures (as referenced in the paper).\r\n'Supplementary
Table 1. Statistics.xlsx'\r\n\tDetails on statistical tests performed in the paper.\r\n'Supplementary
Table 2. Differentially expressed gene analysis.xlsx'\r\n\tResults for the differential
gene expression analysis for embryonic (E9.5; analysis with edgeR) and in vitro
(ESCs, EBs, NPCs; analysis with DESeq2) samples.\r\n'Supplementary Table 3. Gene
Ontology (GO) term enrichment analysis.xlsx'\r\n\tResults for the GO term enrichment
analysis for differentially expressed genes in embryonic (GO E9.5) and in vitro
(GO ESC, GO EBs, GO NPCs) samples. Differentially expressed genes for in vitro
samples were split into upregulated and downregulated genes (up/down) and the
analysis was performed on each subset (e.g. GO ESC up / GO ESC down).\r\n'Supplementary
Table 4. Differentially expressed gene analysis for CFC samples.xlsx'\r\n\tResults
for the differential gene expression analysis for samples from adult mice before
(HC - Homecage) and 1h and 3h after contextual fear conditioning (1h and 3h, respectively).
Each sheet shows the results for a different comparison. Sheets 1-3 show results
for comparisons between timepoints for wild type (WT) samples only and sheets
4-6 for the same comparisons in mutant (Het) samples. Sheets 7-9 show results
for comparisons between genotypes at each time point and sheet 10 contains the
results for the analysis of differential expression trajectories between wild
type and mutant.\r\n'Supplementary Table 5. Cluster identification.xlsx'\r\n\tResults
for k-means clustering of genes by expression. Sheet 1 shows clustering of just
the genes with significantly different expression trajectories between genotypes.
Sheet 2 shows clustering of all genes that are significantly differentially expressed
in any of the comparisons (includes also genes with same trajectories).\r\n'Supplementary
Table 6. GO term cluster analysis.xlsx'\r\n\tResults for the GO term enrichment
analysis and EWCE analysis for enrichment of cell type specific genes for each
cluster identified by clustering genes with different expression trajectories
(see Table S5, sheet 1).\r\n'Supplementary Table 7. Setd5 mass spectrometry results.xlsx'\r\n\tResults
showing proteins interacting with Setd5 as identified by mass spectrometry. Sheet
1 shows protein protein interaction data generated from these results (combined
with data from the STRING database. Sheet 2 shows the results of the statistical
analysis with limma.\r\n'Supplementary Table 8. PolII ChIP-seq analysis.xlsx'\r\n\tResults
for the Chip-Seq analysis for binding of RNA polymerase II (PolII). Sheet 1 shows
results for differential binding of PolII at the transcription start site (TSS)
between genotypes and sheets 2+3 show the corresponding GO enrichment analysis
for these differentially bound genes. Sheet 4 shows RNAseq counts for genes with
increased binding of PolII at the TSS."
article_processing_charge: No
author:
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Dotter C, Novarino G. Supplementary data for the research paper “Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition.” 2019. doi:10.15479/AT:ISTA:6074
apa: Dotter, C., & Novarino, G. (2019). Supplementary data for the research
paper “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental
gene expression and cognition.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6074
chicago: Dotter, Christoph, and Gaia Novarino. “Supplementary Data for the Research
Paper ‘Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental
Gene Expression and Cognition.’” Institute of Science and Technology Austria,
2019. https://doi.org/10.15479/AT:ISTA:6074.
ieee: C. Dotter and G. Novarino, “Supplementary data for the research paper ‘Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition.’” Institute of Science and Technology Austria, 2019.
ista: Dotter C, Novarino G. 2019. Supplementary data for the research paper ‘Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:6074.
mla: Dotter, Christoph, and Gaia Novarino. Supplementary Data for the Research
Paper “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental
Gene Expression and Cognition.” Institute of Science and Technology Austria,
2019, doi:10.15479/AT:ISTA:6074.
short: C. Dotter, G. Novarino, (2019).
date_created: 2019-03-07T13:32:35Z
date_published: 2019-01-09T00:00:00Z
date_updated: 2024-02-21T13:41:01Z
day: '09'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.15479/AT:ISTA:6074
file:
- access_level: open_access
checksum: bc1b285edca9e98a2c63d153c79bb75b
content_type: application/zip
creator: dernst
date_created: 2019-03-07T13:37:19Z
date_updated: 2020-07-14T12:47:18Z
file_id: '6084'
file_name: Setd5_paper.zip
file_size: 33202743
relation: supplementary_material
file_date_updated: 2020-07-14T12:47:18Z
has_accepted_license: '1'
month: '01'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '3'
relation: research_paper
status: public
status: public
title: Supplementary data for the research paper "Haploinsufficiency of the intellectual
disability gene SETD5 disturbs developmental gene expression and cognition"
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '3'
abstract:
- lang: eng
text: SETD5 gene mutations have been identified as a frequent cause of idiopathic
intellectual disability. Here we show that Setd5-haploinsufficient mice present
developmental defects such as abnormal brain-to-body weight ratios and neural
crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments
in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile
of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are
accompanied by abnormal expression of postsynaptic density proteins previously
associated with cognition. Our data additionally indicate that Setd5 regulates
RNA polymerase II dynamics and gene transcription via its interaction with the
Hdac3 and Paf1 complexes, findings potentially explaining the gene expression
defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive
role of Setd5 in a biological pathway found to be disrupted in humans with intellectual
disability and autism spectrum disorder.
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
acknowledgement: This work was supported by the Simons Foundation Autism Research
Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.
article_processing_charge: No
article_type: original
author:
- first_name: Elena
full_name: Deliu, Elena
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Niccoló
full_name: Arecco, Niccoló
last_name: Arecco
- first_name: Jasmin
full_name: Morandell, Jasmin
id: 4739D480-F248-11E8-B48F-1D18A9856A87
last_name: Morandell
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Ximena
full_name: Contreras, Ximena
id: 475990FE-F248-11E8-B48F-1D18A9856A87
last_name: Contreras
- first_name: Charles
full_name: Girardot, Charles
last_name: Girardot
- first_name: Eva
full_name: Käsper, Eva
last_name: Käsper
- first_name: Alena
full_name: Kozlova, Alena
id: C50A9596-02D0-11E9-976E-E38CFE5CBC1D
last_name: Kozlova
- first_name: Kasumi
full_name: Kishi, Kasumi
id: 3065DFC4-F248-11E8-B48F-1D18A9856A87
last_name: Kishi
- first_name: Ilaria
full_name: Chiaradia, Ilaria
id: B6467F20-02D0-11E9-BDA5-E960C241894A
last_name: Chiaradia
orcid: 0000-0002-9529-4464
- first_name: Kyung
full_name: Noh, Kyung
last_name: Noh
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual
disability gene SETD5 disturbs developmental gene expression and cognition. Nature
Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2
apa: Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot,
C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene
SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience.
Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2
chicago: Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena
Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual
Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature
Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2.
ieee: E. Deliu et al., “Haploinsufficiency of the intellectual disability
gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience,
vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.
ista: Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper
E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency
of the intellectual disability gene SETD5 disturbs developmental gene expression
and cognition. Nature Neuroscience. 21(12), 1717–1727.
mla: Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene
SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience,
vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2.
short: E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot,
E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience
21 (2018) 1717–1727.
date_created: 2018-12-11T11:44:05Z
date_published: 2018-11-19T00:00:00Z
date_updated: 2024-03-25T23:30:25Z
day: '19'
ddc:
- '570'
department:
- _id: GaNo
- _id: EdHa
doi: 10.1038/s41593-018-0266-2
external_id:
isi:
- '000451324700010'
file:
- access_level: open_access
checksum: 60abd0f05b7cdc08a6b0ec460884084f
content_type: application/pdf
creator: dernst
date_created: 2019-04-09T07:41:57Z
date_updated: 2020-07-14T12:45:58Z
file_id: '6255'
file_name: 2017_NatureNeuroscience_Deliu.pdf
file_size: 8167169
relation: main_file
file_date_updated: 2020-07-14T12:45:58Z
has_accepted_license: '1'
intvolume: ' 21'
isi: 1
issue: '12'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Submitted Version
page: 1717 - 1727
project:
- _id: 254BA948-B435-11E9-9278-68D0E5697425
grant_number: '401299'
name: Probing development and reversibility of autism spectrum disorders
publication: Nature Neuroscience
publication_status: published
publisher: Nature Publishing Group
publist_id: '8054'
pubrep_id: '1071'
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/
record:
- id: '6074'
relation: popular_science
status: public
- id: '12364'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental
gene expression and cognition
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 21
year: '2018'
...
---
_id: '713'
abstract:
- lang: eng
text: To determine the dynamics of allelic-specific expression during mouse development,
we analyzed RNA-seq data from 23 F1 tissues from different developmental stages,
including 19 female tissues allowing X chromosome inactivation (XCI) escapers
to also be detected. We demonstrate that allelic expression arising from genetic
or epigenetic differences is highly tissue-specific. We find that tissue-specific
strain-biased gene expression may be regulated by tissue-specific enhancers or
by post-transcriptional differences in stability between the alleles. We also
find that escape from X-inactivation is tissue-specific, with leg muscle showing
an unexpectedly high rate of XCI escapers. By surveying a range of tissues during
development, and performing extensive validation, we are able to provide a high
confidence list of mouse imprinted genes including 18 novel genes. This shows
that cluster size varies dynamically during development and can be substantially
larger than previously thought, with the Igf2r cluster extending over 10 Mb in
placenta.
article_number: e25125
author:
- first_name: Daniel
full_name: Andergassen, Daniel
last_name: Andergassen
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
- first_name: Dyniel
full_name: Wenzel, Dyniel
last_name: Wenzel
- first_name: Verena
full_name: Sigl, Verena
last_name: Sigl
- first_name: Philipp
full_name: Bammer, Philipp
last_name: Bammer
- first_name: Markus
full_name: Muckenhuber, Markus
last_name: Muckenhuber
- first_name: Daniela
full_name: Mayer, Daniela
last_name: Mayer
- first_name: Tomasz
full_name: Kulinski, Tomasz
last_name: Kulinski
- first_name: Hans
full_name: Theussl, Hans
last_name: Theussl
- first_name: Josef
full_name: Penninger, Josef
last_name: Penninger
- first_name: Christoph
full_name: Bock, Christoph
last_name: Bock
- first_name: Denise
full_name: Barlow, Denise
last_name: Barlow
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Quanah
full_name: Hudson, Quanah
last_name: Hudson
citation:
ama: Andergassen D, Dotter C, Wenzel D, et al. Mapping the mouse Allelome reveals
tissue specific regulation of allelic expression. eLife. 2017;6. doi:10.7554/eLife.25125
apa: Andergassen, D., Dotter, C., Wenzel, D., Sigl, V., Bammer, P., Muckenhuber,
M., … Hudson, Q. (2017). Mapping the mouse Allelome reveals tissue specific regulation
of allelic expression. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25125
chicago: Andergassen, Daniel, Christoph Dotter, Dyniel Wenzel, Verena Sigl, Philipp
Bammer, Markus Muckenhuber, Daniela Mayer, et al. “Mapping the Mouse Allelome
Reveals Tissue Specific Regulation of Allelic Expression.” ELife. eLife
Sciences Publications, 2017. https://doi.org/10.7554/eLife.25125.
ieee: D. Andergassen et al., “Mapping the mouse Allelome reveals tissue specific
regulation of allelic expression,” eLife, vol. 6. eLife Sciences Publications,
2017.
ista: Andergassen D, Dotter C, Wenzel D, Sigl V, Bammer P, Muckenhuber M, Mayer
D, Kulinski T, Theussl H, Penninger J, Bock C, Barlow D, Pauler F, Hudson Q. 2017.
Mapping the mouse Allelome reveals tissue specific regulation of allelic expression.
eLife. 6, e25125.
mla: Andergassen, Daniel, et al. “Mapping the Mouse Allelome Reveals Tissue Specific
Regulation of Allelic Expression.” ELife, vol. 6, e25125, eLife Sciences
Publications, 2017, doi:10.7554/eLife.25125.
short: D. Andergassen, C. Dotter, D. Wenzel, V. Sigl, P. Bammer, M. Muckenhuber,
D. Mayer, T. Kulinski, H. Theussl, J. Penninger, C. Bock, D. Barlow, F. Pauler,
Q. Hudson, ELife 6 (2017).
date_created: 2018-12-11T11:48:05Z
date_published: 2017-08-14T00:00:00Z
date_updated: 2021-01-12T08:11:57Z
day: '14'
ddc:
- '576'
department:
- _id: GaNo
- _id: SiHi
doi: 10.7554/eLife.25125
file:
- access_level: open_access
checksum: 1ace3462e64a971b9ead896091829549
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:13:36Z
date_updated: 2020-07-14T12:47:50Z
file_id: '5020'
file_name: IST-2017-885-v1+1_elife-25125-figures-v2.pdf
file_size: 6399510
relation: main_file
- access_level: open_access
checksum: 6241dc31eeb87b03facadec3a53a6827
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:13:36Z
date_updated: 2020-07-14T12:47:50Z
file_id: '5021'
file_name: IST-2017-885-v1+2_elife-25125-v2.pdf
file_size: 4264398
relation: main_file
file_date_updated: 2020-07-14T12:47:50Z
has_accepted_license: '1'
intvolume: ' 6'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
publication: eLife
publication_identifier:
issn:
- 2050084X
publication_status: published
publisher: eLife Sciences Publications
publist_id: '6971'
pubrep_id: '885'
quality_controlled: '1'
scopus_import: 1
status: public
title: Mapping the mouse Allelome reveals tissue specific regulation of allelic expression
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2017'
...
---
_id: '1183'
abstract:
- lang: eng
text: Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping
with other neurological conditions. We previously described abnormalities in the
branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we
show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid
transporter localized at the blood brain barrier (BBB), has an essential role
in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from
the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal
mRNA translation, and severe neurological abnormalities. Furthermore, we identified
several patients with autistic traits and motor delay carrying deleterious homozygous
mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular
administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate
a neurological syndrome defined by SLC7A5 mutations and support an essential role
for the BCAA in human brain function.
acknowledgement: "This work was supported by NICHD (P01HD070494) and SFARI (grant
275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\nWe thank A.C. Manzano, Mike Liu,
and F. Marr for technical assistance, and R. Shigemoto and the IST Austria Electron
Microscopy (EM) Facility for assistance. We acknowledge support from CIDR for genome-wide
SNP analysis (X01HG008823) and Broad Institute Center for Mendelian Disorders (UM1HG008900
to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to M.G.),
the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.), Italian Ministry of Instruction
University and Research (PON01_00937 to C.I.), and NIH (R01-GM108911 to A.S.). This
work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and
FWF (SFB35_3523) to G.N.\r\n\r\n#EMFacility"
article_processing_charge: No
article_type: original
author:
- first_name: Dora-Clara
full_name: Tarlungeanu, Dora-Clara
id: 2ABCE612-F248-11E8-B48F-1D18A9856A87
last_name: Tarlungeanu
- first_name: Elena
full_name: Deliu, Elena
id: 37A40D7E-F248-11E8-B48F-1D18A9856A87
last_name: Deliu
orcid: 0000-0002-7370-5293
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
orcid: 0000-0002-9033-9096
- first_name: Majdi
full_name: Kara, Majdi
last_name: Kara
- first_name: Philipp
full_name: Janiesch, Philipp
last_name: Janiesch
- first_name: Mariafrancesca
full_name: Scalise, Mariafrancesca
last_name: Scalise
- first_name: Michele
full_name: Galluccio, Michele
last_name: Galluccio
- first_name: Mateja
full_name: Tesulov, Mateja
last_name: Tesulov
- first_name: Emanuela
full_name: Morelli, Emanuela
id: 3F4D1282-F248-11E8-B48F-1D18A9856A87
last_name: Morelli
- first_name: Fatma
full_name: Sönmez, Fatma
last_name: Sönmez
- first_name: Kaya
full_name: Bilgüvar, Kaya
last_name: Bilgüvar
- first_name: Ryuichi
full_name: Ohgaki, Ryuichi
last_name: Ohgaki
- first_name: Yoshikatsu
full_name: Kanai, Yoshikatsu
last_name: Kanai
- first_name: Anide
full_name: Johansen, Anide
last_name: Johansen
- first_name: Seham
full_name: Esharif, Seham
last_name: Esharif
- first_name: Tawfeg
full_name: Ben Omran, Tawfeg
last_name: Ben Omran
- first_name: Meral
full_name: Topcu, Meral
last_name: Topcu
- first_name: Avner
full_name: Schlessinger, Avner
last_name: Schlessinger
- first_name: Cesare
full_name: Indiveri, Cesare
last_name: Indiveri
- first_name: Kent
full_name: Duncan, Kent
last_name: Duncan
- first_name: Ahmet
full_name: Caglayan, Ahmet
last_name: Caglayan
- first_name: Murat
full_name: Günel, Murat
last_name: Günel
- first_name: Joseph
full_name: Gleeson, Joseph
last_name: Gleeson
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
citation:
ama: Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at
the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494.
doi:10.1016/j.cell.2016.11.013
apa: Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise,
M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier
is a cause of autism spectrum disorder. Cell. Cell Press. https://doi.org/10.1016/j.cell.2016.11.013
chicago: Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp
Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid
Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.”
Cell. Cell Press, 2016. https://doi.org/10.1016/j.cell.2016.11.013.
ieee: D.-C. Tarlungeanu et al., “Impaired amino acid transport at the blood
brain barrier is a cause of autism spectrum disorder,” Cell, vol. 167,
no. 6. Cell Press, pp. 1481–1494, 2016.
ista: Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio
M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A,
Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan
A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the
blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494.
mla: Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood
Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell, vol. 167,
no. 6, Cell Press, 2016, pp. 1481–94, doi:10.1016/j.cell.2016.11.013.
short: D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise,
M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai,
A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri,
K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494.
date_created: 2018-12-11T11:50:35Z
date_published: 2016-12-01T00:00:00Z
date_updated: 2024-03-25T23:30:07Z
day: '01'
ddc:
- '576'
- '616'
department:
- _id: GaNo
doi: 10.1016/j.cell.2016.11.013
file:
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checksum: 7fe01ab12a6610d3db421e0136db2f77
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creator: system
date_created: 2018-12-12T10:13:44Z
date_updated: 2020-07-14T12:44:37Z
file_id: '5030'
file_name: IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf
file_size: 73907957
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file_date_updated: 2020-07-14T12:44:37Z
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intvolume: ' 167'
issue: '6'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Submitted Version
page: 1481 - 1494
project:
- _id: 25473368-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: F03523
name: Transmembrane Transporters in Health and Disease
publication: Cell
publication_status: published
publisher: Cell Press
publist_id: '6170'
pubrep_id: '771'
quality_controlled: '1'
related_material:
record:
- id: '395'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Impaired amino acid transport at the blood brain barrier is a cause of autism
spectrum disorder
type: journal_article
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
volume: 167
year: '2016'
...
---
_id: '1240'
abstract:
- lang: eng
text: 'Background: Long non-coding RNAs (lncRNAs) are increasingly implicated as
gene regulators and may ultimately be more numerous than protein-coding genes
in the human genome. Despite large numbers of reported lncRNAs, reference annotations
are likely incomplete due to their lower and tighter tissue-specific expression
compared to mRNAs. An unexplored factor potentially confounding lncRNA identification
is inter-individual expression variability. Here, we characterize lncRNA natural
expression variability in human primary granulocytes. Results: We annotate granulocyte
lncRNAs and mRNAs in RNA-seq data from 10 healthy individuals, identifying multiple
lncRNAs absent from reference annotations, and use this to investigate three known
features (higher tissue-specificity, lower expression, and reduced splicing efficiency)
of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals
sampled three times at 1- or more than 1-month intervals. We show that lncRNAs
display significantly more inter-individual expression variability compared to
mRNAs. We confirm this finding in two independent human datasets by analyzing
multiple tissues from the GTEx project and lymphoblastoid cell lines from the
GEUVADIS project. Using the latter dataset we also show that including more human
donors into the transcriptome annotation pipeline allows identification of an
increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions:
A comprehensive annotation of lncRNAs is known to require an approach that is
sensitive to low and tight tissue-specific expression. Here we show that increased
inter-individual expression variability is an additional general lncRNA feature
to consider when creating a comprehensive annotation of human lncRNAs or proposing
their use as prognostic or disease markers.'
acknowledgement: "This study was partly funded by the Austrian Science Fund (FWF F43-B09,
FWF W1207-B09). PMG is a recipient of a DOC Fellowship of the Austrian Academy of
Sciences.\r\nWe thank Ruth Klement, Tomasz Kulinski, Elisangela Valente, Elisabeth
Salzer,\r\nand Roland Jäger for technical/bioinformatic assistance and advice, the
CeMM\r\nIT department and José Manuel Molero for help and advice on software usage,\r\nthe
Biomedical Sequencing Facility (http://biomedical-sequencing.at/) for\r\nsequencing
and advice, Jacques Colinge, Daniel Andergassen, and Tomasz\r\nKulinski for discussions,
Quanah Hudson and Jörg Menche for reading and\r\ncommenting on the manuscript."
article_number: '14'
author:
- first_name: Aleksandra
full_name: Kornienko, Aleksandra
last_name: Kornienko
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
- first_name: Philipp
full_name: Guenzl, Philipp
last_name: Guenzl
- first_name: Heinz
full_name: Gisslinger, Heinz
last_name: Gisslinger
- first_name: Bettina
full_name: Gisslinger, Bettina
last_name: Gisslinger
- first_name: Ciara
full_name: Cleary, Ciara
last_name: Cleary
- first_name: Robert
full_name: Kralovics, Robert
last_name: Kralovics
- first_name: Florian
full_name: Pauler, Florian
id: 48EA0138-F248-11E8-B48F-1D18A9856A87
last_name: Pauler
- first_name: Denise
full_name: Barlow, Denise
last_name: Barlow
citation:
ama: Kornienko A, Dotter C, Guenzl P, et al. Long non-coding RNAs display higher
natural expression variation than protein-coding genes in healthy humans. Genome
Biology. 2016;17(1). doi:10.1186/s13059-016-0873-8
apa: Kornienko, A., Dotter, C., Guenzl, P., Gisslinger, H., Gisslinger, B., Cleary,
C., … Barlow, D. (2016). Long non-coding RNAs display higher natural expression
variation than protein-coding genes in healthy humans. Genome Biology.
BioMed Central. https://doi.org/10.1186/s13059-016-0873-8
chicago: Kornienko, Aleksandra, Christoph Dotter, Philipp Guenzl, Heinz Gisslinger,
Bettina Gisslinger, Ciara Cleary, Robert Kralovics, Florian Pauler, and Denise
Barlow. “Long Non-Coding RNAs Display Higher Natural Expression Variation than
Protein-Coding Genes in Healthy Humans.” Genome Biology. BioMed Central,
2016. https://doi.org/10.1186/s13059-016-0873-8.
ieee: A. Kornienko et al., “Long non-coding RNAs display higher natural expression
variation than protein-coding genes in healthy humans,” Genome Biology,
vol. 17, no. 1. BioMed Central, 2016.
ista: Kornienko A, Dotter C, Guenzl P, Gisslinger H, Gisslinger B, Cleary C, Kralovics
R, Pauler F, Barlow D. 2016. Long non-coding RNAs display higher natural expression
variation than protein-coding genes in healthy humans. Genome Biology. 17(1),
14.
mla: Kornienko, Aleksandra, et al. “Long Non-Coding RNAs Display Higher Natural
Expression Variation than Protein-Coding Genes in Healthy Humans.” Genome Biology,
vol. 17, no. 1, 14, BioMed Central, 2016, doi:10.1186/s13059-016-0873-8.
short: A. Kornienko, C. Dotter, P. Guenzl, H. Gisslinger, B. Gisslinger, C. Cleary,
R. Kralovics, F. Pauler, D. Barlow, Genome Biology 17 (2016).
date_created: 2018-12-11T11:50:53Z
date_published: 2016-01-29T00:00:00Z
date_updated: 2021-01-12T06:49:20Z
day: '29'
ddc:
- '576'
department:
- _id: GaNo
doi: 10.1186/s13059-016-0873-8
file:
- access_level: open_access
checksum: a268beee1a690801c83ec6729f9ebc5b
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:10:05Z
date_updated: 2020-07-14T12:44:41Z
file_id: '4789'
file_name: IST-2016-709-v1+1_s13059-016-0873-8.pdf
file_size: 2914601
relation: main_file
file_date_updated: 2020-07-14T12:44:41Z
has_accepted_license: '1'
intvolume: ' 17'
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
publication: Genome Biology
publication_status: published
publisher: BioMed Central
publist_id: '6093'
pubrep_id: '709'
quality_controlled: '1'
scopus_import: 1
status: public
title: Long non-coding RNAs display higher natural expression variation than protein-coding
genes in healthy humans
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2016'
...
---
_id: '1497'
abstract:
- lang: eng
text: Detecting allelic biases from high-throughput sequencing data requires an
approach that maximises sensitivity while minimizing false positives. Here, we
present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which
uses high-throughput sequencing data from reciprocal crosses of two genetically
distinct mouse strains to detect allele-specific expression and chromatin modifications.
Allelome.PRO extends approaches used in previous studies that exclusively analyzed
imprinted expression to give a complete picture of the ‘allelome’ by automatically
categorising the allelic expression of all genes in a given cell type into imprinted,
strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity
to analyze lowly expressed transcripts, together with a robust false discovery
rate empirically calculated from variation in the sequencing data. We used RNA-seq
data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine
a biologically relevant allelic ratio cutoff, and define for the first time an
entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment
of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This
approach can be easily extended to analyze histone marks of active enhancers,
or transcription factor binding sites and therefore provides a powerful tool to
identify candidate cis regulatory elements genome wide.
acknowledgement: "Austrian Science Fund [FWF P25185-B22, FWF F4302- B09, FWFW1207-B09].
Funding for open access charge: Austrian Science Fund.\r\nWe thank Florian Breitwieser
for advice during the early stages of this project. High-throughput sequencing was
conducted by the Biomedical Sequencing Facility (BSF) at CeMM in Vienna."
article_number: e146
author:
- first_name: Daniel
full_name: Andergassen, Daniel
last_name: Andergassen
- first_name: Christoph
full_name: Dotter, Christoph
id: 4C66542E-F248-11E8-B48F-1D18A9856A87
last_name: Dotter
- first_name: Tomasz
full_name: Kulinski, Tomasz
last_name: Kulinski
- first_name: Philipp
full_name: Guenzl, Philipp
last_name: Guenzl
- first_name: Philipp
full_name: Bammer, Philipp
last_name: Bammer
- first_name: Denise
full_name: Barlow, Denise
last_name: Barlow
- first_name: Florian
full_name: Pauler, Florian
last_name: Pauler
- first_name: Quanah
full_name: Hudson, Quanah
last_name: Hudson
citation:
ama: Andergassen D, Dotter C, Kulinski T, et al. Allelome.PRO, a pipeline to define
allele-specific genomic features from high-throughput sequencing data. Nucleic
Acids Research. 2015;43(21). doi:10.1093/nar/gkv727
apa: Andergassen, D., Dotter, C., Kulinski, T., Guenzl, P., Bammer, P., Barlow,
D., … Hudson, Q. (2015). Allelome.PRO, a pipeline to define allele-specific genomic
features from high-throughput sequencing data. Nucleic Acids Research.
Oxford University Press. https://doi.org/10.1093/nar/gkv727
chicago: Andergassen, Daniel, Christoph Dotter, Tomasz Kulinski, Philipp Guenzl,
Philipp Bammer, Denise Barlow, Florian Pauler, and Quanah Hudson. “Allelome.PRO,
a Pipeline to Define Allele-Specific Genomic Features from High-Throughput Sequencing
Data.” Nucleic Acids Research. Oxford University Press, 2015. https://doi.org/10.1093/nar/gkv727.
ieee: D. Andergassen et al., “Allelome.PRO, a pipeline to define allele-specific
genomic features from high-throughput sequencing data,” Nucleic Acids Research,
vol. 43, no. 21. Oxford University Press, 2015.
ista: Andergassen D, Dotter C, Kulinski T, Guenzl P, Bammer P, Barlow D, Pauler
F, Hudson Q. 2015. Allelome.PRO, a pipeline to define allele-specific genomic
features from high-throughput sequencing data. Nucleic Acids Research. 43(21),
e146.
mla: Andergassen, Daniel, et al. “Allelome.PRO, a Pipeline to Define Allele-Specific
Genomic Features from High-Throughput Sequencing Data.” Nucleic Acids Research,
vol. 43, no. 21, e146, Oxford University Press, 2015, doi:10.1093/nar/gkv727.
short: D. Andergassen, C. Dotter, T. Kulinski, P. Guenzl, P. Bammer, D. Barlow,
F. Pauler, Q. Hudson, Nucleic Acids Research 43 (2015).
date_created: 2018-12-11T11:52:22Z
date_published: 2015-07-21T00:00:00Z
date_updated: 2021-01-12T06:51:09Z
day: '21'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1093/nar/gkv727
file:
- access_level: open_access
checksum: 385b83854fd0eb2e4f386867da2823e2
content_type: application/pdf
creator: dernst
date_created: 2018-12-20T14:18:57Z
date_updated: 2020-07-14T12:44:58Z
file_id: '5768'
file_name: 2015_NucleicAcidsRes_Andergassen.pdf
file_size: 6863297
relation: main_file
file_date_updated: 2020-07-14T12:44:58Z
has_accepted_license: '1'
intvolume: ' 43'
issue: '21'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
publication: Nucleic Acids Research
publication_status: published
publisher: Oxford University Press
publist_id: '5682'
quality_controlled: '1'
scopus_import: 1
status: public
title: Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput
sequencing data
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 43
year: '2015'
...