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Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice

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Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice. / Spielmann, Malte; Kakar, Naseebullah; Tayebi, Naeimeh; Leettola, Catherine; Nürnberg, Gudrun; Sowada, Nadine; Lupiáñez, Darío G; Harabula, Izabela; Flöttmann, Ricarda; Horn, Denise; Chan, Wing Lee; Wittler, Lars; Yilmaz, Rüstem; Altmüller, Janine; Thiele, Holger; van Bokhoven, Hans; Schwartz, Charles E; Nürnberg, Peter; Bowie, James U; Ahmad, Jamil; Kubisch, Christian; Mundlos, Stefan; Borck, Guntram.

in: GENOME RES, Jahrgang 26, Nr. 2, 02.2016, S. 183-91.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Spielmann, M, Kakar, N, Tayebi, N, Leettola, C, Nürnberg, G, Sowada, N, Lupiáñez, DG, Harabula, I, Flöttmann, R, Horn, D, Chan, WL, Wittler, L, Yilmaz, R, Altmüller, J, Thiele, H, van Bokhoven, H, Schwartz, CE, Nürnberg, P, Bowie, JU, Ahmad, J, Kubisch, C, Mundlos, S & Borck, G 2016, 'Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice', GENOME RES, Jg. 26, Nr. 2, S. 183-91. https://doi.org/10.1101/gr.199430.115

APA

Spielmann, M., Kakar, N., Tayebi, N., Leettola, C., Nürnberg, G., Sowada, N., Lupiáñez, D. G., Harabula, I., Flöttmann, R., Horn, D., Chan, W. L., Wittler, L., Yilmaz, R., Altmüller, J., Thiele, H., van Bokhoven, H., Schwartz, C. E., Nürnberg, P., Bowie, J. U., ... Borck, G. (2016). Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice. GENOME RES, 26(2), 183-91. https://doi.org/10.1101/gr.199430.115

Vancouver

Spielmann M, Kakar N, Tayebi N, Leettola C, Nürnberg G, Sowada N et al. Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice. GENOME RES. 2016 Feb;26(2):183-91. https://doi.org/10.1101/gr.199430.115

Bibtex

@article{35fdd413b28841d8b083413b48bed5c5,
title = "Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice",
abstract = "The CRISPR/Cas technology enables targeted genome editing and the rapid generation of transgenic animal models for the study of human genetic disorders. Here we describe an autosomal recessive human disease in two unrelated families characterized by a split-foot defect, nail abnormalities of the hands, and hearing loss, due to mutations disrupting the SAM domain of the protein kinase ZAK. ZAK is a member of the MAPKKK family with no known role in limb development. We show that Zak is expressed in the developing limbs and that a CRISPR/Cas-mediated knockout of the two Zak isoforms is embryonically lethal in mice. In contrast, a deletion of the SAM domain induces a complex hindlimb defect associated with down-regulation of Trp63, a known split-hand/split-foot malformation disease gene. Our results identify ZAK as a key player in mammalian limb patterning and demonstrate the rapid utility of CRISPR/Cas genome editing to assign causality to human mutations in the mouse in <10 wk.",
author = "Malte Spielmann and Naseebullah Kakar and Naeimeh Tayebi and Catherine Leettola and Gudrun N{\"u}rnberg and Nadine Sowada and Lupi{\'a}{\~n}ez, {Dar{\'i}o G} and Izabela Harabula and Ricarda Fl{\"o}ttmann and Denise Horn and Chan, {Wing Lee} and Lars Wittler and R{\"u}stem Yilmaz and Janine Altm{\"u}ller and Holger Thiele and {van Bokhoven}, Hans and Schwartz, {Charles E} and Peter N{\"u}rnberg and Bowie, {James U} and Jamil Ahmad and Christian Kubisch and Stefan Mundlos and Guntram Borck",
note = "{\textcopyright} 2016 Spielmann et al.; Published by Cold Spring Harbor Laboratory Press.",
year = "2016",
month = feb,
doi = "10.1101/gr.199430.115",
language = "English",
volume = "26",
pages = "183--91",
journal = "GENOME RES",
issn = "1088-9051",
publisher = "Cold Spring Harbor Laboratory Press",
number = "2",

}

RIS

TY - JOUR

T1 - Exome sequencing and CRISPR/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice

AU - Spielmann, Malte

AU - Kakar, Naseebullah

AU - Tayebi, Naeimeh

AU - Leettola, Catherine

AU - Nürnberg, Gudrun

AU - Sowada, Nadine

AU - Lupiáñez, Darío G

AU - Harabula, Izabela

AU - Flöttmann, Ricarda

AU - Horn, Denise

AU - Chan, Wing Lee

AU - Wittler, Lars

AU - Yilmaz, Rüstem

AU - Altmüller, Janine

AU - Thiele, Holger

AU - van Bokhoven, Hans

AU - Schwartz, Charles E

AU - Nürnberg, Peter

AU - Bowie, James U

AU - Ahmad, Jamil

AU - Kubisch, Christian

AU - Mundlos, Stefan

AU - Borck, Guntram

N1 - © 2016 Spielmann et al.; Published by Cold Spring Harbor Laboratory Press.

PY - 2016/2

Y1 - 2016/2

N2 - The CRISPR/Cas technology enables targeted genome editing and the rapid generation of transgenic animal models for the study of human genetic disorders. Here we describe an autosomal recessive human disease in two unrelated families characterized by a split-foot defect, nail abnormalities of the hands, and hearing loss, due to mutations disrupting the SAM domain of the protein kinase ZAK. ZAK is a member of the MAPKKK family with no known role in limb development. We show that Zak is expressed in the developing limbs and that a CRISPR/Cas-mediated knockout of the two Zak isoforms is embryonically lethal in mice. In contrast, a deletion of the SAM domain induces a complex hindlimb defect associated with down-regulation of Trp63, a known split-hand/split-foot malformation disease gene. Our results identify ZAK as a key player in mammalian limb patterning and demonstrate the rapid utility of CRISPR/Cas genome editing to assign causality to human mutations in the mouse in <10 wk.

AB - The CRISPR/Cas technology enables targeted genome editing and the rapid generation of transgenic animal models for the study of human genetic disorders. Here we describe an autosomal recessive human disease in two unrelated families characterized by a split-foot defect, nail abnormalities of the hands, and hearing loss, due to mutations disrupting the SAM domain of the protein kinase ZAK. ZAK is a member of the MAPKKK family with no known role in limb development. We show that Zak is expressed in the developing limbs and that a CRISPR/Cas-mediated knockout of the two Zak isoforms is embryonically lethal in mice. In contrast, a deletion of the SAM domain induces a complex hindlimb defect associated with down-regulation of Trp63, a known split-hand/split-foot malformation disease gene. Our results identify ZAK as a key player in mammalian limb patterning and demonstrate the rapid utility of CRISPR/Cas genome editing to assign causality to human mutations in the mouse in <10 wk.

U2 - 10.1101/gr.199430.115

DO - 10.1101/gr.199430.115

M3 - SCORING: Journal article

C2 - 26755636

VL - 26

SP - 183

EP - 191

JO - GENOME RES

JF - GENOME RES

SN - 1088-9051

IS - 2

ER -