---
_id: '14368'
abstract:
- lang: eng
text: "Purpose: \r\nBiallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase,
have been reported in a small group of individuals displaying a neurodevelopmental
phenotype but with limited neuroradiological data and insufficient evidence for
causality of the variants.\r\nMethods:\r\nExome or genome sequencing was carried
out in 15 families. Clinical and neuroradiological evaluation was performed for
all affected individuals, including review of 10 previously reported individuals.
The pathogenicity of TARS2 variants was evaluated using in vitro assays and a
zebrafish model.\r\nResults:\r\nWe report 18 new individuals harboring biallelic
TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual
disability, regression, cerebellar and cerebral atrophy, basal ganglia signal
alterations, hypotonia, cerebellar signs, and increased blood lactate. In vitro
studies showed that variants within the TARS2301-381 region had decreased binding
to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated
key features of the human phenotype and unraveled dysregulation of downstream
targets of mTORC1 signaling. Functional testing of the variants confirmed the
pathogenicity in a zebrafish model.\r\nConclusion:\r\nWe define the clinico-radiological
spectrum of TARS2-related mitochondrial disease, unveil the likely involvement
of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish
a TARS2 zebrafish model as an important tool to study variant pathogenicity."
article_number: '100938'
article_processing_charge: No
article_type: original
author:
- first_name: Andrea
full_name: Accogli, Andrea
last_name: Accogli
- first_name: Sheng-Jia
full_name: Lin, Sheng-Jia
last_name: Lin
- first_name: Mariasavina
full_name: Severino, Mariasavina
last_name: Severino
- first_name: Sung-Hoon
full_name: Kim, Sung-Hoon
last_name: Kim
- first_name: Kevin
full_name: Huang, Kevin
id: 3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3
last_name: Huang
orcid: 0000-0002-2512-7812
- first_name: Clarissa
full_name: Rocca, Clarissa
last_name: Rocca
- first_name: Megan
full_name: Landsverk, Megan
last_name: Landsverk
- first_name: Maha S.
full_name: Zaki, Maha S.
last_name: Zaki
- first_name: Almundher
full_name: Al-Maawali, Almundher
last_name: Al-Maawali
- first_name: Varunvenkat M.
full_name: Srinivasan, Varunvenkat M.
last_name: Srinivasan
- first_name: Khalid
full_name: Al-Thihli, Khalid
last_name: Al-Thihli
- first_name: G. Bradly
full_name: Schaefer, G. Bradly
last_name: Schaefer
- first_name: Monica
full_name: Davis, Monica
last_name: Davis
- first_name: Davide
full_name: Tonduti, Davide
last_name: Tonduti
- first_name: Chiara
full_name: Doneda, Chiara
last_name: Doneda
- first_name: Lara M.
full_name: Marten, Lara M.
last_name: Marten
- first_name: Chris
full_name: Mühlhausen, Chris
last_name: Mühlhausen
- first_name: Maria
full_name: Gomez, Maria
last_name: Gomez
- first_name: Eleonora
full_name: Lamantea, Eleonora
last_name: Lamantea
- first_name: Rafael
full_name: Mena, Rafael
last_name: Mena
- first_name: Mathilde
full_name: Nizon, Mathilde
last_name: Nizon
- first_name: Vincent
full_name: Procaccio, Vincent
last_name: Procaccio
- first_name: Amber
full_name: Begtrup, Amber
last_name: Begtrup
- first_name: Aida
full_name: Telegrafi, Aida
last_name: Telegrafi
- first_name: Hong
full_name: Cui, Hong
last_name: Cui
- first_name: Heidi L.
full_name: Schulz, Heidi L.
last_name: Schulz
- first_name: Julia
full_name: Mohr, Julia
last_name: Mohr
- first_name: Saskia
full_name: Biskup, Saskia
last_name: Biskup
- first_name: Mariana Amina
full_name: Loos, Mariana Amina
last_name: Loos
- first_name: Hilda Verónica
full_name: Aráoz, Hilda Verónica
last_name: Aráoz
- first_name: Vincenzo
full_name: Salpietro, Vincenzo
last_name: Salpietro
- first_name: Laura Davis
full_name: Keppen, Laura Davis
last_name: Keppen
- first_name: Manali
full_name: Chitre, Manali
last_name: Chitre
- first_name: Cassidy
full_name: Petree, Cassidy
last_name: Petree
- first_name: Lucy
full_name: Raymond, Lucy
last_name: Raymond
- first_name: Julie
full_name: Vogt, Julie
last_name: Vogt
- first_name: Lindsey B.
full_name: Sawyer, Lindsey B.
last_name: Sawyer
- first_name: Alice A.
full_name: Basinger, Alice A.
last_name: Basinger
- first_name: Signe Vandal
full_name: Pedersen, Signe Vandal
last_name: Pedersen
- first_name: Toni S.
full_name: Pearson, Toni S.
last_name: Pearson
- first_name: Dorothy K.
full_name: Grange, Dorothy K.
last_name: Grange
- first_name: Lokesh
full_name: Lingappa, Lokesh
last_name: Lingappa
- first_name: Paige
full_name: McDunnah, Paige
last_name: McDunnah
- first_name: Rita
full_name: Horvath, Rita
last_name: Horvath
- first_name: Benjamin
full_name: Cognè, Benjamin
last_name: Cognè
- first_name: Bertrand
full_name: Isidor, Bertrand
last_name: Isidor
- first_name: Andreas
full_name: Hahn, Andreas
last_name: Hahn
- first_name: Karen W.
full_name: Gripp, Karen W.
last_name: Gripp
- first_name: Seyed Mehdi
full_name: Jafarnejad, Seyed Mehdi
last_name: Jafarnejad
- first_name: Elsebet
full_name: Østergaard, Elsebet
last_name: Østergaard
- first_name: Carlos E.
full_name: Prada, Carlos E.
last_name: Prada
- first_name: Daniele
full_name: Ghezzi, Daniele
last_name: Ghezzi
- first_name: Vykuntaraju K.
full_name: Gowda, Vykuntaraju K.
last_name: Gowda
- first_name: Robert W.
full_name: Taylor, Robert W.
last_name: Taylor
- first_name: Nahum
full_name: Sonenberg, Nahum
last_name: Sonenberg
- first_name: Henry
full_name: Houlden, Henry
last_name: Houlden
- first_name: Marie
full_name: Sissler, Marie
last_name: Sissler
- first_name: Gaurav K.
full_name: Varshney, Gaurav K.
last_name: Varshney
- first_name: Reza
full_name: Maroofian, Reza
last_name: Maroofian
citation:
ama: Accogli A, Lin S-J, Severino M, et al. Clinical, neuroradiological, and molecular
characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder.
Genetics in Medicine. 2023;25(11). doi:10.1016/j.gim.2023.100938
apa: Accogli, A., Lin, S.-J., Severino, M., Kim, S.-H., Huang, K., Rocca, C., …
Maroofian, R. (2023). Clinical, neuroradiological, and molecular characterization
of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. Genetics
in Medicine. Elsevier. https://doi.org/10.1016/j.gim.2023.100938
chicago: Accogli, Andrea, Sheng-Jia Lin, Mariasavina Severino, Sung-Hoon Kim, Kevin
Huang, Clarissa Rocca, Megan Landsverk, et al. “Clinical, Neuroradiological, and
Molecular Characterization of Mitochondrial Threonyl-TRNA-Synthetase (TARS2)-Related
Disorder.” Genetics in Medicine. Elsevier, 2023. https://doi.org/10.1016/j.gim.2023.100938.
ieee: A. Accogli et al., “Clinical, neuroradiological, and molecular characterization
of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder,” Genetics
in Medicine, vol. 25, no. 11. Elsevier, 2023.
ista: Accogli A, Lin S-J, Severino M, Kim S-H, Huang K, Rocca C, Landsverk M, Zaki
MS, Al-Maawali A, Srinivasan VM, Al-Thihli K, Schaefer GB, Davis M, Tonduti D,
Doneda C, Marten LM, Mühlhausen C, Gomez M, Lamantea E, Mena R, Nizon M, Procaccio
V, Begtrup A, Telegrafi A, Cui H, Schulz HL, Mohr J, Biskup S, Loos MA, Aráoz
HV, Salpietro V, Keppen LD, Chitre M, Petree C, Raymond L, Vogt J, Sawyer LB,
Basinger AA, Pedersen SV, Pearson TS, Grange DK, Lingappa L, McDunnah P, Horvath
R, Cognè B, Isidor B, Hahn A, Gripp KW, Jafarnejad SM, Østergaard E, Prada CE,
Ghezzi D, Gowda VK, Taylor RW, Sonenberg N, Houlden H, Sissler M, Varshney GK,
Maroofian R. 2023. Clinical, neuroradiological, and molecular characterization
of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. Genetics in
Medicine. 25(11), 100938.
mla: Accogli, Andrea, et al. “Clinical, Neuroradiological, and Molecular Characterization
of Mitochondrial Threonyl-TRNA-Synthetase (TARS2)-Related Disorder.” Genetics
in Medicine, vol. 25, no. 11, 100938, Elsevier, 2023, doi:10.1016/j.gim.2023.100938.
short: A. Accogli, S.-J. Lin, M. Severino, S.-H. Kim, K. Huang, C. Rocca, M. Landsverk,
M.S. Zaki, A. Al-Maawali, V.M. Srinivasan, K. Al-Thihli, G.B. Schaefer, M. Davis,
D. Tonduti, C. Doneda, L.M. Marten, C. Mühlhausen, M. Gomez, E. Lamantea, R. Mena,
M. Nizon, V. Procaccio, A. Begtrup, A. Telegrafi, H. Cui, H.L. Schulz, J. Mohr,
S. Biskup, M.A. Loos, H.V. Aráoz, V. Salpietro, L.D. Keppen, M. Chitre, C. Petree,
L. Raymond, J. Vogt, L.B. Sawyer, A.A. Basinger, S.V. Pedersen, T.S. Pearson,
D.K. Grange, L. Lingappa, P. McDunnah, R. Horvath, B. Cognè, B. Isidor, A. Hahn,
K.W. Gripp, S.M. Jafarnejad, E. Østergaard, C.E. Prada, D. Ghezzi, V.K. Gowda,
R.W. Taylor, N. Sonenberg, H. Houlden, M. Sissler, G.K. Varshney, R. Maroofian,
Genetics in Medicine 25 (2023).
date_created: 2023-09-25T08:44:29Z
date_published: 2023-11-01T00:00:00Z
date_updated: 2023-09-25T08:50:10Z
day: '01'
ddc:
- '570'
doi: 10.1016/j.gim.2023.100938
extern: '1'
file:
- access_level: open_access
checksum: 440f0cd8a2ffcbe03c015c1746728387
content_type: application/pdf
creator: dernst
date_created: 2023-09-25T08:48:54Z
date_updated: 2023-09-25T08:48:54Z
file_id: '14369'
file_name: 2023_GeneticsMedicine_Accogli.pdf
file_size: 4105513
relation: main_file
success: 1
file_date_updated: 2023-09-25T08:48:54Z
has_accepted_license: '1'
intvolume: ' 25'
issue: '11'
keyword:
- Genetics (clinical)
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '11'
oa: 1
oa_version: Published Version
publication: Genetics in Medicine
publication_identifier:
issn:
- 1098-3600
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Clinical, neuroradiological, and molecular characterization of mitochondrial
threonyl-tRNA-synthetase (TARS2)-related disorder
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: 25
year: '2023'
...
---
_id: '14639'
abstract:
- lang: eng
text: "Background: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate
dehydrogenase complex, have been associated with highly heterogeneous neurological
and neurodevelopmental disorders. However, the validity of this association remains
to be confirmed. A second OGDHL patient cohort was recruited to carefully assess
the gene-disease relationship.\r\nMethods: Using an unbiased genotype-first approach,
we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic
OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl,
ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during
development. Functional complementation with patient variant transcripts was conducted
to systematically assess protein functionality as a readout for pathogenicity.\r\nResults:
A cohort of 14 individuals from 12 unrelated families exhibited highly variable
clinical phenotypes, with the majority of them presenting at least one additional
variant, potentially accounting for a blended phenotype and complicating phenotypic
understanding. We also uncovered extreme clinical heterogeneity and high allele
frequencies, occasionally incompatible with a fully penetrant recessive disorder.
Human cDNA of previously described and new variants were tested in an ogdhl zebrafish
knockout model, adding functional evidence for variant reclassification. We disclosed
evidence of hypomorphic alleles as well as a loss-of-function variant without
deleterious effects in zebrafish variant testing also showing discordant familial
segregation, challenging the relationship of OGDHL as a conventional Mendelian
gene. Going further, we uncovered evidence for a complex compensatory relationship
among OGDH, OGDHL, and DHTKD1 isoenzymes that are associated with neurodevelopmental
disorders and exhibit complex transcriptional compensation patterns with partial
functional redundancy.\r\nConclusions: Based on the results of genetic, clinical,
and functional studies, we formed three hypotheses in which to frame observations:
biallelic OGDHL variants lead to a highly variable monogenic disorder, variants
in OGDHL are following a complex pattern of inheritance, or they may not be causative
at all. Our study further highlights the continuing challenges of assessing the
validity of reported disease-gene associations and effects of variants identified
in these genes. This is particularly more complicated in making genetic diagnoses
based on identification of variants in genes presenting a highly heterogenous
phenotype such as “OGDHL-related disorders”."
article_number: '102'
article_processing_charge: Yes
article_type: original
author:
- first_name: Sheng-Jia
full_name: Lin, Sheng-Jia
last_name: Lin
- first_name: Barbara
full_name: Vona, Barbara
last_name: Vona
- first_name: Tracy
full_name: Lau, Tracy
last_name: Lau
- first_name: Kevin
full_name: Huang, Kevin
id: 3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3
last_name: Huang
orcid: 0000-0002-2512-7812
- first_name: Maha S.
full_name: Zaki, Maha S.
last_name: Zaki
- first_name: Huda Shujaa
full_name: Aldeen, Huda Shujaa
last_name: Aldeen
- first_name: Ehsan Ghayoor
full_name: Karimiani, Ehsan Ghayoor
last_name: Karimiani
- first_name: Clarissa
full_name: Rocca, Clarissa
last_name: Rocca
- first_name: Mahmoud M.
full_name: Noureldeen, Mahmoud M.
last_name: Noureldeen
- first_name: Ahmed K.
full_name: Saad, Ahmed K.
last_name: Saad
- first_name: Cassidy
full_name: Petree, Cassidy
last_name: Petree
- first_name: Tobias
full_name: Bartolomaeus, Tobias
last_name: Bartolomaeus
- first_name: Rami
full_name: Abou Jamra, Rami
last_name: Abou Jamra
- first_name: Giovanni
full_name: Zifarelli, Giovanni
last_name: Zifarelli
- first_name: Aditi
full_name: Gotkhindikar, Aditi
last_name: Gotkhindikar
- first_name: Ingrid M.
full_name: Wentzensen, Ingrid M.
last_name: Wentzensen
- first_name: Mingjuan
full_name: Liao, Mingjuan
last_name: Liao
- first_name: Emalyn Elise
full_name: Cork, Emalyn Elise
last_name: Cork
- first_name: Pratishtha
full_name: Varshney, Pratishtha
last_name: Varshney
- first_name: Narges
full_name: Hashemi, Narges
last_name: Hashemi
- first_name: Mohammad Hasan
full_name: Mohammadi, Mohammad Hasan
last_name: Mohammadi
- first_name: Aboulfazl
full_name: Rad, Aboulfazl
last_name: Rad
- first_name: Juanita
full_name: Neira, Juanita
last_name: Neira
- first_name: Mehran Beiraghi
full_name: Toosi, Mehran Beiraghi
last_name: Toosi
- first_name: Cordula
full_name: Knopp, Cordula
last_name: Knopp
- first_name: Ingo
full_name: Kurth, Ingo
last_name: Kurth
- first_name: Thomas D.
full_name: Challman, Thomas D.
last_name: Challman
- first_name: Rebecca
full_name: Smith, Rebecca
last_name: Smith
- first_name: Asmahan
full_name: Abdalla, Asmahan
last_name: Abdalla
- first_name: Thomas
full_name: Haaf, Thomas
last_name: Haaf
- first_name: Mohnish
full_name: Suri, Mohnish
last_name: Suri
- first_name: Manali
full_name: Joshi, Manali
last_name: Joshi
- first_name: Wendy K.
full_name: Chung, Wendy K.
last_name: Chung
- first_name: Andres
full_name: Moreno-De-Luca, Andres
last_name: Moreno-De-Luca
- first_name: Henry
full_name: Houlden, Henry
last_name: Houlden
- first_name: Reza
full_name: Maroofian, Reza
last_name: Maroofian
- first_name: Gaurav K.
full_name: Varshney, Gaurav K.
last_name: Varshney
citation:
ama: Lin S-J, Vona B, Lau T, et al. Evaluating the association of biallelic OGDHL
variants with significant phenotypic heterogeneity. Genome Medicine. 2023;15.
doi:10.1186/s13073-023-01258-4
apa: Lin, S.-J., Vona, B., Lau, T., Huang, K., Zaki, M. S., Aldeen, H. S., … Varshney,
G. K. (2023). Evaluating the association of biallelic OGDHL variants with significant
phenotypic heterogeneity. Genome Medicine. Springer Nature. https://doi.org/10.1186/s13073-023-01258-4
chicago: Lin, Sheng-Jia, Barbara Vona, Tracy Lau, Kevin Huang, Maha S. Zaki, Huda
Shujaa Aldeen, Ehsan Ghayoor Karimiani, et al. “Evaluating the Association of
Biallelic OGDHL Variants with Significant Phenotypic Heterogeneity.” Genome
Medicine. Springer Nature, 2023. https://doi.org/10.1186/s13073-023-01258-4.
ieee: S.-J. Lin et al., “Evaluating the association of biallelic OGDHL variants
with significant phenotypic heterogeneity,” Genome Medicine, vol. 15. Springer
Nature, 2023.
ista: Lin S-J, Vona B, Lau T, Huang K, Zaki MS, Aldeen HS, Karimiani EG, Rocca C,
Noureldeen MM, Saad AK, Petree C, Bartolomaeus T, Abou Jamra R, Zifarelli G, Gotkhindikar
A, Wentzensen IM, Liao M, Cork EE, Varshney P, Hashemi N, Mohammadi MH, Rad A,
Neira J, Toosi MB, Knopp C, Kurth I, Challman TD, Smith R, Abdalla A, Haaf T,
Suri M, Joshi M, Chung WK, Moreno-De-Luca A, Houlden H, Maroofian R, Varshney
GK. 2023. Evaluating the association of biallelic OGDHL variants with significant
phenotypic heterogeneity. Genome Medicine. 15, 102.
mla: Lin, Sheng-Jia, et al. “Evaluating the Association of Biallelic OGDHL Variants
with Significant Phenotypic Heterogeneity.” Genome Medicine, vol. 15, 102,
Springer Nature, 2023, doi:10.1186/s13073-023-01258-4.
short: S.-J. Lin, B. Vona, T. Lau, K. Huang, M.S. Zaki, H.S. Aldeen, E.G. Karimiani,
C. Rocca, M.M. Noureldeen, A.K. Saad, C. Petree, T. Bartolomaeus, R. Abou Jamra,
G. Zifarelli, A. Gotkhindikar, I.M. Wentzensen, M. Liao, E.E. Cork, P. Varshney,
N. Hashemi, M.H. Mohammadi, A. Rad, J. Neira, M.B. Toosi, C. Knopp, I. Kurth,
T.D. Challman, R. Smith, A. Abdalla, T. Haaf, M. Suri, M. Joshi, W.K. Chung, A.
Moreno-De-Luca, H. Houlden, R. Maroofian, G.K. Varshney, Genome Medicine 15 (2023).
date_created: 2023-12-04T08:10:55Z
date_published: 2023-11-23T00:00:00Z
date_updated: 2023-12-04T08:17:22Z
day: '23'
ddc:
- '570'
doi: 10.1186/s13073-023-01258-4
extern: '1'
file:
- access_level: open_access
checksum: 279efd212005549aba817a487d56d363
content_type: application/pdf
creator: dernst
date_created: 2023-12-04T08:15:43Z
date_updated: 2023-12-04T08:15:43Z
file_id: '14640'
file_name: 2023_GenomeMed_Lin.pdf
file_size: 14791081
relation: main_file
success: 1
file_date_updated: 2023-12-04T08:15:43Z
has_accepted_license: '1'
intvolume: ' 15'
keyword:
- Genetics (clinical)
- Genetics
- Molecular Biology
- Molecular Medicine
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
publication: Genome Medicine
publication_identifier:
issn:
- 1756-994X
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
status: public
title: Evaluating the association of biallelic OGDHL variants with significant phenotypic
heterogeneity
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: 15
year: '2023'
...
---
_id: '14077'
abstract:
- lang: eng
text: "The regulatory architecture of gene expression is known to differ substantially
between sexes in Drosophila, but most studies performed\r\nso far used whole-body
data and only single crosses, which may have limited their scope to detect patterns
that are robust across tissues\r\nand biological replicates. Here, we use allele-specific
gene expression of parental and reciprocal hybrid crosses between 6 Drosophila\r\nmelanogaster
inbred lines to quantify cis- and trans-regulatory variation in heads and gonads
of both sexes separately across 3 replicate\r\ncrosses. Our results suggest that
female and male heads, as well as ovaries, have a similar regulatory architecture.
On the other hand,\r\ntestes display more and substantially different cis-regulatory
effects, suggesting that sex differences in the regulatory architecture that\r\nhave
been previously observed may largely derive from testis-specific effects. We also
examine the difference in cis-regulatory variation\r\nof genes across different
levels of sex bias in gonads and heads. Consistent with the idea that intersex
correlations constrain expression\r\nand can lead to sexual antagonism, we find
more cis variation in unbiased and moderately biased genes in heads. In ovaries,
reduced cis\r\nvariation is observed for male-biased genes, suggesting that cis
variants acting on these genes in males do not lead to changes in ovary\r\nexpression.
Finally, we examine the dominance patterns of gene expression and find that sex-
and tissue-specific patterns of inheritance\r\nas well as trans-regulatory variation
are highly variable across biological crosses, although these were performed in
highly controlled\r\nexperimental conditions. This highlights the importance of
using various genetic backgrounds to infer generalizable patterns."
acknowledged_ssus:
- _id: ScienComp
acknowledgement: We thank members of the Vicoso Group for comments on the manuscript,
the Scientific Computing Unit at ISTA for technical support, and 2 anonymous reviewers
for useful feedback. GP is the recipient of a DOC Fellowship of the Austrian Academy
of Sciences at the Institute of Science and Technology Austria (DOC 25817) and received
funding from the European Union’s Horizon 2020 research and innovation program under
the Marie Skłodowska-Curie Grant (agreement no. 665385).
article_processing_charge: Yes
article_type: original
author:
- first_name: Gemma
full_name: Puixeu Sala, Gemma
id: 33AB266C-F248-11E8-B48F-1D18A9856A87
last_name: Puixeu Sala
orcid: 0000-0001-8330-1754
- first_name: Ariana
full_name: Macon, Ariana
id: 2A0848E2-F248-11E8-B48F-1D18A9856A87
last_name: Macon
- first_name: Beatriz
full_name: Vicoso, Beatriz
id: 49E1C5C6-F248-11E8-B48F-1D18A9856A87
last_name: Vicoso
orcid: 0000-0002-4579-8306
citation:
ama: 'Puixeu Sala G, Macon A, Vicoso B. Sex-specific estimation of cis and trans
regulation of gene expression in heads and gonads of Drosophila melanogaster.
G3: Genes, Genomes, Genetics. 2023;13(8). doi:10.1093/g3journal/jkad121'
apa: 'Puixeu Sala, G., Macon, A., & Vicoso, B. (2023). Sex-specific estimation
of cis and trans regulation of gene expression in heads and gonads of Drosophila
melanogaster. G3: Genes, Genomes, Genetics. Oxford University Press. https://doi.org/10.1093/g3journal/jkad121'
chicago: 'Puixeu Sala, Gemma, Ariana Macon, and Beatriz Vicoso. “Sex-Specific Estimation
of Cis and Trans Regulation of Gene Expression in Heads and Gonads of Drosophila
Melanogaster.” G3: Genes, Genomes, Genetics. Oxford University Press, 2023.
https://doi.org/10.1093/g3journal/jkad121.'
ieee: 'G. Puixeu Sala, A. Macon, and B. Vicoso, “Sex-specific estimation of cis
and trans regulation of gene expression in heads and gonads of Drosophila melanogaster,”
G3: Genes, Genomes, Genetics, vol. 13, no. 8. Oxford University Press,
2023.'
ista: 'Puixeu Sala G, Macon A, Vicoso B. 2023. Sex-specific estimation of cis and
trans regulation of gene expression in heads and gonads of Drosophila melanogaster.
G3: Genes, Genomes, Genetics. 13(8).'
mla: 'Puixeu Sala, Gemma, et al. “Sex-Specific Estimation of Cis and Trans Regulation
of Gene Expression in Heads and Gonads of Drosophila Melanogaster.” G3: Genes,
Genomes, Genetics, vol. 13, no. 8, Oxford University Press, 2023, doi:10.1093/g3journal/jkad121.'
short: 'G. Puixeu Sala, A. Macon, B. Vicoso, G3: Genes, Genomes, Genetics 13 (2023).'
date_created: 2023-08-18T06:52:14Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2023-12-13T12:15:37Z
day: '01'
ddc:
- '570'
department:
- _id: BeVi
- _id: NiBa
- _id: GradSch
doi: 10.1093/g3journal/jkad121
ec_funded: 1
external_id:
isi:
- '001002997200001'
file:
- access_level: open_access
checksum: c62e29fc7c5efbf8356f4c60cab4a2d1
content_type: application/pdf
creator: dernst
date_created: 2023-11-07T09:00:19Z
date_updated: 2023-11-07T09:00:19Z
file_id: '14498'
file_name: 2023_G3_Puixeu.pdf
file_size: 845642
relation: main_file
success: 1
file_date_updated: 2023-11-07T09:00:19Z
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
issue: '8'
keyword:
- Genetics (clinical)
- Genetics
- Molecular Biology
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 9B9DFC9E-BA93-11EA-9121-9846C619BF3A
grant_number: '25817'
name: 'Sexual conflict: resolution, constraints and biomedical implications'
publication: 'G3: Genes, Genomes, Genetics'
publication_identifier:
issn:
- 2160-1836
publication_status: published
publisher: Oxford University Press
quality_controlled: '1'
related_material:
record:
- id: '12933'
relation: research_data
status: public
- id: '14058'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Sex-specific estimation of cis and trans regulation of gene expression in heads
and gonads of Drosophila melanogaster
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: 13
year: '2023'
...
---
_id: '12142'
abstract:
- lang: eng
text: Theory for liability-scale models of the underlying genetic basis of complex
disease provides an important way to interpret, compare, and understand results
generated from biological studies. In particular, through estimation of the liability-scale
heritability (LSH), liability models facilitate an understanding and comparison
of the relative importance of genetic and environmental risk factors that shape
different clinically important disease outcomes. Increasingly, large-scale biobank
studies that link genetic information to electronic health records, containing
hundreds of disease diagnosis indicators that mostly occur infrequently within
the sample, are becoming available. Here, we propose an extension of the existing
liability-scale model theory suitable for estimating LSH in biobank studies of
low-prevalence disease. In a simulation study, we find that our derived expression
yields lower mean square error (MSE) and is less sensitive to prevalence misspecification
as compared to previous transformations for diseases with =< 2% population prevalence
and LSH of =< 0.45, especially if the biobank sample prevalence is less than that
of the wider population. Applying our expression to 13 diagnostic outcomes of =<
3% prevalence in the UK Biobank study revealed important differences in LSH obtained
from the different theoretical expressions that impact the conclusions made when
comparing LSH across disease outcomes. This demonstrates the importance of careful
consideration for estimation and prediction of low-prevalence disease outcomes
and facilitates improved inference of the underlying genetic basis of =< 2% population
prevalence diseases, especially where biobank sample ascertainment results in
a healthier sample population.
acknowledged_ssus:
- _id: ScienComp
acknowledgement: This project was funded by an SNSF Eccellenza grant to M.R.R. (PCEGP3-181181),
core funding from the Institute of Science and Technology Austria, and core funding
from the Department of Computational Biology of the University of Lausanne. Z.K.
was funded by the Swiss National Science Foundation (310030-189147). This research
was supported by the Scientific Service Units (SSUs) of IST Austria through resources
provided by Scientific Computing (SciComp). We would like to thank the participants
of the UK Biobank.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Sven E.
full_name: Ojavee, Sven E.
last_name: Ojavee
- first_name: Zoltan
full_name: Kutalik, Zoltan
last_name: Kutalik
- first_name: Matthew Richard
full_name: Robinson, Matthew Richard
id: E5D42276-F5DA-11E9-8E24-6303E6697425
last_name: Robinson
orcid: 0000-0001-8982-8813
citation:
ama: Ojavee SE, Kutalik Z, Robinson MR. Liability-scale heritability estimation
for biobank studies of low-prevalence disease. The American Journal of Human
Genetics. 2022;109(11):2009-2017. doi:10.1016/j.ajhg.2022.09.011
apa: Ojavee, S. E., Kutalik, Z., & Robinson, M. R. (2022). Liability-scale heritability
estimation for biobank studies of low-prevalence disease. The American Journal
of Human Genetics. Elsevier. https://doi.org/10.1016/j.ajhg.2022.09.011
chicago: Ojavee, Sven E., Zoltan Kutalik, and Matthew Richard Robinson. “Liability-Scale
Heritability Estimation for Biobank Studies of Low-Prevalence Disease.” The
American Journal of Human Genetics. Elsevier, 2022. https://doi.org/10.1016/j.ajhg.2022.09.011.
ieee: S. E. Ojavee, Z. Kutalik, and M. R. Robinson, “Liability-scale heritability
estimation for biobank studies of low-prevalence disease,” The American Journal
of Human Genetics, vol. 109, no. 11. Elsevier, pp. 2009–2017, 2022.
ista: Ojavee SE, Kutalik Z, Robinson MR. 2022. Liability-scale heritability estimation
for biobank studies of low-prevalence disease. The American Journal of Human Genetics.
109(11), 2009–2017.
mla: Ojavee, Sven E., et al. “Liability-Scale Heritability Estimation for Biobank
Studies of Low-Prevalence Disease.” The American Journal of Human Genetics,
vol. 109, no. 11, Elsevier, 2022, pp. 2009–17, doi:10.1016/j.ajhg.2022.09.011.
short: S.E. Ojavee, Z. Kutalik, M.R. Robinson, The American Journal of Human Genetics
109 (2022) 2009–2017.
date_created: 2023-01-12T12:05:28Z
date_published: 2022-11-03T00:00:00Z
date_updated: 2023-08-04T08:56:46Z
day: '03'
ddc:
- '570'
department:
- _id: MaRo
doi: 10.1016/j.ajhg.2022.09.011
external_id:
isi:
- '000898683500006'
file:
- access_level: open_access
checksum: 4cd7f12bfe21a8237bb095eedfa26361
content_type: application/pdf
creator: dernst
date_created: 2023-01-24T09:23:01Z
date_updated: 2023-01-24T09:23:01Z
file_id: '12353'
file_name: 2022_AJHG_Ojavee.pdf
file_size: 705195
relation: main_file
success: 1
file_date_updated: 2023-01-24T09:23:01Z
has_accepted_license: '1'
intvolume: ' 109'
isi: 1
issue: '11'
keyword:
- Genetics (clinical)
- Genetics
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '11'
oa: 1
oa_version: Published Version
page: 2009-2017
project:
- _id: 9B8D11D6-BA93-11EA-9121-9846C619BF3A
grant_number: PCEGP3_181181
name: Improving estimation and prediction of common complex disease risk
publication: The American Journal of Human Genetics
publication_identifier:
issn:
- 0002-9297
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: Liability-scale heritability estimation for biobank studies of low-prevalence
disease
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 109
year: '2022'
...
---
_id: '12189'
abstract:
- lang: eng
text: Meiotic crossovers (COs) are important for reshuffling genetic information
between homologous chromosomes and they are essential for their correct segregation.
COs are unevenly distributed along chromosomes and the underlying mechanisms controlling
CO localization are not well understood. We previously showed that meiotic COs
are mis-localized in the absence of AXR1, an enzyme involved in the neddylation/rubylation
protein modification pathway in Arabidopsis thaliana. Here, we report that in
axr1-/-, male meiocytes show a strong defect in chromosome pairing whereas the
formation of the telomere bouquet is not affected. COs are also redistributed
towards subtelomeric chromosomal ends where they frequently form clusters, in
contrast to large central regions depleted in recombination. The CO suppressed
regions correlate with DNA hypermethylation of transposable elements (TEs) in
the CHH context in axr1-/- meiocytes. Through examining somatic methylomes, we
found axr1-/- affects DNA methylation in a plant, causing hypermethylation in
all sequence contexts (CG, CHG and CHH) in TEs. Impairment of the main pathways
involved in DNA methylation is epistatic over axr1-/- for DNA methylation in somatic
cells but does not restore regular chromosome segregation during meiosis. Collectively,
our findings reveal that the neddylation pathway not only regulates hormonal perception
and CO distribution but is also, directly or indirectly, a major limiting pathway
of TE DNA methylation in somatic cells.
acknowledgement: The authors wish to thank Cécile Raynaud, Eric Jenczewski, Rajeev
Kumar, Raphaël Mercier and Jean Molinier for critical reading of the manuscript.
article_number: e1008894
article_processing_charge: No
article_type: original
author:
- first_name: Nicolas
full_name: Christophorou, Nicolas
last_name: Christophorou
- first_name: Wenjing
full_name: She, Wenjing
last_name: She
- first_name: Jincheng
full_name: Long, Jincheng
last_name: Long
- first_name: Aurélie
full_name: Hurel, Aurélie
last_name: Hurel
- first_name: Sébastien
full_name: Beaubiat, Sébastien
last_name: Beaubiat
- first_name: Yassir
full_name: Idir, Yassir
last_name: Idir
- first_name: Marina
full_name: Tagliaro-Jahns, Marina
last_name: Tagliaro-Jahns
- first_name: Aurélie
full_name: Chambon, Aurélie
last_name: Chambon
- first_name: Victor
full_name: Solier, Victor
last_name: Solier
- first_name: Daniel
full_name: Vezon, Daniel
last_name: Vezon
- first_name: Mathilde
full_name: Grelon, Mathilde
last_name: Grelon
- first_name: Xiaoqi
full_name: Feng, Xiaoqi
id: e0164712-22ee-11ed-b12a-d80fcdf35958
last_name: Feng
orcid: 0000-0002-4008-1234
- first_name: Nicolas
full_name: Bouché, Nicolas
last_name: Bouché
- first_name: Christine
full_name: Mézard, Christine
last_name: Mézard
citation:
ama: Christophorou N, She W, Long J, et al. AXR1 affects DNA methylation independently
of its role in regulating meiotic crossover localization. PLOS Genetics.
2020;16(6). doi:10.1371/journal.pgen.1008894
apa: Christophorou, N., She, W., Long, J., Hurel, A., Beaubiat, S., Idir, Y., …
Mézard, C. (2020). AXR1 affects DNA methylation independently of its role in regulating
meiotic crossover localization. PLOS Genetics. Public Library of Science
(PLoS). https://doi.org/10.1371/journal.pgen.1008894
chicago: Christophorou, Nicolas, Wenjing She, Jincheng Long, Aurélie Hurel, Sébastien
Beaubiat, Yassir Idir, Marina Tagliaro-Jahns, et al. “AXR1 Affects DNA Methylation
Independently of Its Role in Regulating Meiotic Crossover Localization.” PLOS
Genetics. Public Library of Science (PLoS), 2020. https://doi.org/10.1371/journal.pgen.1008894.
ieee: N. Christophorou et al., “AXR1 affects DNA methylation independently
of its role in regulating meiotic crossover localization,” PLOS Genetics,
vol. 16, no. 6. Public Library of Science (PLoS), 2020.
ista: Christophorou N, She W, Long J, Hurel A, Beaubiat S, Idir Y, Tagliaro-Jahns
M, Chambon A, Solier V, Vezon D, Grelon M, Feng X, Bouché N, Mézard C. 2020. AXR1
affects DNA methylation independently of its role in regulating meiotic crossover
localization. PLOS Genetics. 16(6), e1008894.
mla: Christophorou, Nicolas, et al. “AXR1 Affects DNA Methylation Independently
of Its Role in Regulating Meiotic Crossover Localization.” PLOS Genetics,
vol. 16, no. 6, e1008894, Public Library of Science (PLoS), 2020, doi:10.1371/journal.pgen.1008894.
short: N. Christophorou, W. She, J. Long, A. Hurel, S. Beaubiat, Y. Idir, M. Tagliaro-Jahns,
A. Chambon, V. Solier, D. Vezon, M. Grelon, X. Feng, N. Bouché, C. Mézard, PLOS
Genetics 16 (2020).
date_created: 2023-01-16T09:16:10Z
date_published: 2020-06-29T00:00:00Z
date_updated: 2023-05-08T10:54:39Z
day: '29'
department:
- _id: XiFe
doi: 10.1371/journal.pgen.1008894
extern: '1'
external_id:
pmid:
- '32598340'
intvolume: ' 16'
issue: '6'
keyword:
- Cancer Research
- Genetics (clinical)
- Genetics
- Molecular Biology
- Ecology
- Evolution
- Behavior and Systematics
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351236/
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLOS Genetics
publication_identifier:
issn:
- 1553-7404
publication_status: published
publisher: Public Library of Science (PLoS)
quality_controlled: '1'
scopus_import: '1'
status: public
title: AXR1 affects DNA methylation independently of its role in regulating meiotic
crossover localization
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2020'
...
---
_id: '11059'
abstract:
- lang: eng
text: The genome is packaged and organized nonrandomly within the 3D space of the
nucleus to promote efficient gene expression and to faithfully maintain silencing
of heterochromatin. The genome is enclosed within the nucleus by the nuclear envelope
membrane, which contains a set of proteins that actively participate in chromatin
organization and gene regulation. Technological advances are providing views of
genome organization at unprecedented resolution and are beginning to reveal the
ways that cells co-opt the structures of the nuclear periphery for nuclear organization
and gene regulation. These genome regulatory roles of proteins of the nuclear
periphery have important influences on development, disease and ageing.
article_processing_charge: No
article_type: review
author:
- first_name: Abigail
full_name: Buchwalter, Abigail
last_name: Buchwalter
- first_name: Jeanae M.
full_name: Kaneshiro, Jeanae M.
last_name: Kaneshiro
- first_name: Martin W
full_name: HETZER, Martin W
id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
last_name: HETZER
orcid: 0000-0002-2111-992X
citation:
ama: 'Buchwalter A, Kaneshiro JM, Hetzer M. Coaching from the sidelines: The nuclear
periphery in genome regulation. Nature Reviews Genetics. 2019;20(1):39-50.
doi:10.1038/s41576-018-0063-5'
apa: 'Buchwalter, A., Kaneshiro, J. M., & Hetzer, M. (2019). Coaching from the
sidelines: The nuclear periphery in genome regulation. Nature Reviews Genetics.
Springer Nature. https://doi.org/10.1038/s41576-018-0063-5'
chicago: 'Buchwalter, Abigail, Jeanae M. Kaneshiro, and Martin Hetzer. “Coaching
from the Sidelines: The Nuclear Periphery in Genome Regulation.” Nature Reviews
Genetics. Springer Nature, 2019. https://doi.org/10.1038/s41576-018-0063-5.'
ieee: 'A. Buchwalter, J. M. Kaneshiro, and M. Hetzer, “Coaching from the sidelines:
The nuclear periphery in genome regulation,” Nature Reviews Genetics, vol.
20, no. 1. Springer Nature, pp. 39–50, 2019.'
ista: 'Buchwalter A, Kaneshiro JM, Hetzer M. 2019. Coaching from the sidelines:
The nuclear periphery in genome regulation. Nature Reviews Genetics. 20(1), 39–50.'
mla: 'Buchwalter, Abigail, et al. “Coaching from the Sidelines: The Nuclear Periphery
in Genome Regulation.” Nature Reviews Genetics, vol. 20, no. 1, Springer
Nature, 2019, pp. 39–50, doi:10.1038/s41576-018-0063-5.'
short: A. Buchwalter, J.M. Kaneshiro, M. Hetzer, Nature Reviews Genetics 20 (2019)
39–50.
date_created: 2022-04-07T07:44:45Z
date_published: 2019-01-01T00:00:00Z
date_updated: 2022-07-18T08:31:42Z
day: '01'
doi: 10.1038/s41576-018-0063-5
extern: '1'
external_id:
pmid:
- '30356165'
intvolume: ' 20'
issue: '1'
keyword:
- Genetics (clinical)
- Genetics
- Molecular Biology
language:
- iso: eng
month: '01'
oa_version: None
page: 39-50
pmid: 1
publication: Nature Reviews Genetics
publication_identifier:
eissn:
- 1471-0064
issn:
- 1471-0056
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Coaching from the sidelines: The nuclear periphery in genome regulation'
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 20
year: '2019'
...
---
_id: '11086'
abstract:
- lang: eng
text: Faithful execution of developmental gene expression programs occurs at multiple
levels and involves many different components such as transcription factors, histone-modification
enzymes, and mRNA processing proteins. Recent evidence suggests that nucleoporins,
well known components that control nucleo-cytoplasmic trafficking, have wide-ranging
functions in developmental gene regulation that potentially extend beyond their
role in nuclear transport. Whether the unexpected role of nuclear pore proteins
in transcription regulation, which initially has been described in fungi and flies,
also applies to human cells is unknown. Here we show at a genome-wide level that
the nuclear pore protein NUP98 associates with developmentally regulated genes
active during human embryonic stem cell differentiation. Overexpression of a dominant
negative fragment of NUP98 levels decreases expression levels of NUP98-bound genes.
In addition, we identify two modes of developmental gene regulation by NUP98 that
are differentiated by the spatial localization of NUP98 target genes. Genes in
the initial stage of developmental induction can associate with NUP98 that is
embedded in the nuclear pores at the nuclear periphery. Alternatively, genes that
are highly induced can interact with NUP98 in the nuclear interior, away from
the nuclear pores. This work demonstrates for the first time that NUP98 dynamically
associates with the human genome during differentiation, revealing a role of a
nuclear pore protein in regulating developmental gene expression programs.
article_number: e1003308
article_processing_charge: No
article_type: original
author:
- first_name: Yun
full_name: Liang, Yun
last_name: Liang
- first_name: Tobias M.
full_name: Franks, Tobias M.
last_name: Franks
- first_name: Maria C.
full_name: Marchetto, Maria C.
last_name: Marchetto
- first_name: Fred H.
full_name: Gage, Fred H.
last_name: Gage
- first_name: Martin W
full_name: HETZER, Martin W
id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
last_name: HETZER
orcid: 0000-0002-2111-992X
citation:
ama: Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer M. Dynamic association of
NUP98 with the human genome. PLoS Genetics. 2013;9(2). doi:10.1371/journal.pgen.1003308
apa: Liang, Y., Franks, T. M., Marchetto, M. C., Gage, F. H., & Hetzer, M. (2013).
Dynamic association of NUP98 with the human genome. PLoS Genetics. Public
Library of Science. https://doi.org/10.1371/journal.pgen.1003308
chicago: Liang, Yun, Tobias M. Franks, Maria C. Marchetto, Fred H. Gage, and Martin
Hetzer. “Dynamic Association of NUP98 with the Human Genome.” PLoS Genetics.
Public Library of Science, 2013. https://doi.org/10.1371/journal.pgen.1003308.
ieee: Y. Liang, T. M. Franks, M. C. Marchetto, F. H. Gage, and M. Hetzer, “Dynamic
association of NUP98 with the human genome,” PLoS Genetics, vol. 9, no.
2. Public Library of Science, 2013.
ista: Liang Y, Franks TM, Marchetto MC, Gage FH, Hetzer M. 2013. Dynamic association
of NUP98 with the human genome. PLoS Genetics. 9(2), e1003308.
mla: Liang, Yun, et al. “Dynamic Association of NUP98 with the Human Genome.” PLoS
Genetics, vol. 9, no. 2, e1003308, Public Library of Science, 2013, doi:10.1371/journal.pgen.1003308.
short: Y. Liang, T.M. Franks, M.C. Marchetto, F.H. Gage, M. Hetzer, PLoS Genetics
9 (2013).
date_created: 2022-04-07T07:50:59Z
date_published: 2013-02-28T00:00:00Z
date_updated: 2022-07-18T08:45:58Z
day: '28'
doi: 10.1371/journal.pgen.1003308
extern: '1'
external_id:
pmid:
- '23468646'
intvolume: ' 9'
issue: '2'
keyword:
- Cancer Research
- Genetics (clinical)
- Genetics
- Molecular Biology
- Ecology
- Evolution
- Behavior and Systematics
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1371/journal.pgen.1003308
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: PLoS Genetics
publication_identifier:
issn:
- 1553-7404
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dynamic association of NUP98 with the human genome
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 9
year: '2013'
...
---
_id: '11099'
abstract:
- lang: eng
text: Nuclear pore complexes (NPCs) serve as transport channels across the nuclear
membrane, a double lipid bilayer that physically separates the nucleoplasm and
cytoplasm of eukaryotic cells. New evidence suggests that the multiprotein nuclear
pores also play a role in chromatin organization and gene expression. Given the
importance of NPC function, it is not surprising that a growing list of human
diseases and developmental defects have been linked to its malfunction. In order
to fully understand the functional repertoire of NPCs and their essential role
for nuclear organization, it is critical to determine the sequence of events that
lead to the formation of nuclear pores. This is particularly relevant since NPC
number, and possibly composition, are tightly linked to metabolic activity. Most
of our knowledge is derived from NPC formation that occurs in dividing cells at
the end of mitosis when the nuclear envelope (NE) and NPCs reform from disassembled
precursors. However, NPC assembly also takes place during interphase into an intact
NE. Importantly, this process is not restricted to dividing cells but also occurs
during cell differentiation. Here, we will review aspects unique to this process,
namely the regulation of nuclear expansion and the mechanisms of fusion between
the outer and inner nuclear membranes. We will then discuss conserved and diverging
mechanisms between post-mitotic and interphase assembly of the proteinaceous structure
in light of recently published data.
article_processing_charge: No
article_type: review
author:
- first_name: Christine M.
full_name: Doucet, Christine M.
last_name: Doucet
- first_name: Martin W
full_name: HETZER, Martin W
id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
last_name: HETZER
orcid: 0000-0002-2111-992X
citation:
ama: Doucet CM, Hetzer M. Nuclear pore biogenesis into an intact nuclear envelope.
Chromosoma. 2010;119:469-477. doi:10.1007/s00412-010-0289-2
apa: Doucet, C. M., & Hetzer, M. (2010). Nuclear pore biogenesis into an intact
nuclear envelope. Chromosoma. Springer Nature. https://doi.org/10.1007/s00412-010-0289-2
chicago: Doucet, Christine M., and Martin Hetzer. “Nuclear Pore Biogenesis into
an Intact Nuclear Envelope.” Chromosoma. Springer Nature, 2010. https://doi.org/10.1007/s00412-010-0289-2.
ieee: C. M. Doucet and M. Hetzer, “Nuclear pore biogenesis into an intact nuclear
envelope,” Chromosoma, vol. 119. Springer Nature, pp. 469–477, 2010.
ista: Doucet CM, Hetzer M. 2010. Nuclear pore biogenesis into an intact nuclear
envelope. Chromosoma. 119, 469–477.
mla: Doucet, Christine M., and Martin Hetzer. “Nuclear Pore Biogenesis into an Intact
Nuclear Envelope.” Chromosoma, vol. 119, Springer Nature, 2010, pp. 469–77,
doi:10.1007/s00412-010-0289-2.
short: C.M. Doucet, M. Hetzer, Chromosoma 119 (2010) 469–477.
date_created: 2022-04-07T07:53:12Z
date_published: 2010-10-01T00:00:00Z
date_updated: 2022-07-18T08:54:20Z
day: '01'
doi: 10.1007/s00412-010-0289-2
extern: '1'
external_id:
pmid:
- '20721671'
intvolume: ' 119'
keyword:
- Genetics (clinical)
- Genetics
language:
- iso: eng
month: '10'
oa_version: None
page: 469-477
pmid: 1
publication: Chromosoma
publication_identifier:
eissn:
- 1432-0886
issn:
- 0009-5915
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Nuclear pore biogenesis into an intact nuclear envelope
type: journal_article
user_id: 72615eeb-f1f3-11ec-aa25-d4573ddc34fd
volume: 119
year: '2010'
...