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A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull

Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and ca...

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Autores principales: Capitan, Aurélien, Allais-Bonnet, Aurélie, Pinton, Alain, Marquant-Le Guienne, Brigitte, Le Bourhis, Daniel, Grohs, Cécile, Bouet, Stéphan, Clément, Laëtitia, Salas-Cortes, Laura, Venot, Eric, Chaffaux, Stéphane, Weiss, Bernard, Delpeuch, Arnaud, Noé, Guy, Rossignol, Marie-Noëlle, Barbey, Sarah, Dozias, Dominique, Cobo, Emilie, Barasc, Harmonie, Auguste, Aurélie, Pannetier, Maëlle, Deloche, Marie-Christine, Lhuilier, Emeline, Bouchez, Olivier, Esquerré, Diane, Salin, Gérald, Klopp, Christophe, Donnadieu, Cécile, Chantry-Darmon, Céline, Hayes, Hélène, Gallard, Yves, Ponsart, Claire, Boichard, Didier, Pailhoux, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494662/
https://www.ncbi.nlm.nih.gov/pubmed/23152852
http://dx.doi.org/10.1371/journal.pone.0049084
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author Capitan, Aurélien
Allais-Bonnet, Aurélie
Pinton, Alain
Marquant-Le Guienne, Brigitte
Le Bourhis, Daniel
Grohs, Cécile
Bouet, Stéphan
Clément, Laëtitia
Salas-Cortes, Laura
Venot, Eric
Chaffaux, Stéphane
Weiss, Bernard
Delpeuch, Arnaud
Noé, Guy
Rossignol, Marie-Noëlle
Barbey, Sarah
Dozias, Dominique
Cobo, Emilie
Barasc, Harmonie
Auguste, Aurélie
Pannetier, Maëlle
Deloche, Marie-Christine
Lhuilier, Emeline
Bouchez, Olivier
Esquerré, Diane
Salin, Gérald
Klopp, Christophe
Donnadieu, Cécile
Chantry-Darmon, Céline
Hayes, Hélène
Gallard, Yves
Ponsart, Claire
Boichard, Didier
Pailhoux, Eric
author_facet Capitan, Aurélien
Allais-Bonnet, Aurélie
Pinton, Alain
Marquant-Le Guienne, Brigitte
Le Bourhis, Daniel
Grohs, Cécile
Bouet, Stéphan
Clément, Laëtitia
Salas-Cortes, Laura
Venot, Eric
Chaffaux, Stéphane
Weiss, Bernard
Delpeuch, Arnaud
Noé, Guy
Rossignol, Marie-Noëlle
Barbey, Sarah
Dozias, Dominique
Cobo, Emilie
Barasc, Harmonie
Auguste, Aurélie
Pannetier, Maëlle
Deloche, Marie-Christine
Lhuilier, Emeline
Bouchez, Olivier
Esquerré, Diane
Salin, Gérald
Klopp, Christophe
Donnadieu, Cécile
Chantry-Darmon, Céline
Hayes, Hélène
Gallard, Yves
Ponsart, Claire
Boichard, Didier
Pailhoux, Eric
author_sort Capitan, Aurélien
collection PubMed
description Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping and whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced control and affected 90-day old fetuses to characterize this syndrome by histological and expression analyses. Compared to wild type individuals, affected animals showed a decreased expression of the three deleted genes. Based on a comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation. Finally sperm-FISH, embryo genotyping and analysis of reproduction records confirmed somatic mosaicism in the founder bull and male-specific lethality during the first third of gestation. In conclusion, we identified a novel locus involved in bovid horn ontogenesis and suggest that epithelial-to-mesenchymal transition plays a critical role in horn bud differentiation. We also provide new insights into the pathogenicity of ZEB2 loss of heterozygosity in bovine and humans and describe the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species. This result sets PMS as a unique model to study sex-specific gene expression/regulation.
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spelling pubmed-34946622012-11-14 A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull Capitan, Aurélien Allais-Bonnet, Aurélie Pinton, Alain Marquant-Le Guienne, Brigitte Le Bourhis, Daniel Grohs, Cécile Bouet, Stéphan Clément, Laëtitia Salas-Cortes, Laura Venot, Eric Chaffaux, Stéphane Weiss, Bernard Delpeuch, Arnaud Noé, Guy Rossignol, Marie-Noëlle Barbey, Sarah Dozias, Dominique Cobo, Emilie Barasc, Harmonie Auguste, Aurélie Pannetier, Maëlle Deloche, Marie-Christine Lhuilier, Emeline Bouchez, Olivier Esquerré, Diane Salin, Gérald Klopp, Christophe Donnadieu, Cécile Chantry-Darmon, Céline Hayes, Hélène Gallard, Yves Ponsart, Claire Boichard, Didier Pailhoux, Eric PLoS One Research Article Polled and Multisystemic Syndrome (PMS) is a novel developmental disorder occurring in the progeny of a single bull. Its clinical spectrum includes polledness (complete agenesis of horns), facial dysmorphism, growth delay, chronic diarrhea, premature ovarian failure, and variable neurological and cardiac anomalies. PMS is also characterized by a deviation of the sex-ratio, suggesting male lethality during pregnancy. Using Mendelian error mapping and whole-genome sequencing, we identified a 3.7 Mb deletion on the paternal bovine chromosome 2 encompassing ARHGAP15, GTDC1 and ZEB2 genes. We then produced control and affected 90-day old fetuses to characterize this syndrome by histological and expression analyses. Compared to wild type individuals, affected animals showed a decreased expression of the three deleted genes. Based on a comparison with human Mowat-Wilson syndrome, we suggest that deletion of ZEB2, is responsible for most of the effects of the mutation. Finally sperm-FISH, embryo genotyping and analysis of reproduction records confirmed somatic mosaicism in the founder bull and male-specific lethality during the first third of gestation. In conclusion, we identified a novel locus involved in bovid horn ontogenesis and suggest that epithelial-to-mesenchymal transition plays a critical role in horn bud differentiation. We also provide new insights into the pathogenicity of ZEB2 loss of heterozygosity in bovine and humans and describe the first case of male-specific lethality associated with an autosomal locus in a non-murine mammalian species. This result sets PMS as a unique model to study sex-specific gene expression/regulation. Public Library of Science 2012-11-09 /pmc/articles/PMC3494662/ /pubmed/23152852 http://dx.doi.org/10.1371/journal.pone.0049084 Text en © 2012 Capitan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Capitan, Aurélien
Allais-Bonnet, Aurélie
Pinton, Alain
Marquant-Le Guienne, Brigitte
Le Bourhis, Daniel
Grohs, Cécile
Bouet, Stéphan
Clément, Laëtitia
Salas-Cortes, Laura
Venot, Eric
Chaffaux, Stéphane
Weiss, Bernard
Delpeuch, Arnaud
Noé, Guy
Rossignol, Marie-Noëlle
Barbey, Sarah
Dozias, Dominique
Cobo, Emilie
Barasc, Harmonie
Auguste, Aurélie
Pannetier, Maëlle
Deloche, Marie-Christine
Lhuilier, Emeline
Bouchez, Olivier
Esquerré, Diane
Salin, Gérald
Klopp, Christophe
Donnadieu, Cécile
Chantry-Darmon, Céline
Hayes, Hélène
Gallard, Yves
Ponsart, Claire
Boichard, Didier
Pailhoux, Eric
A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull
title A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull
title_full A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull
title_fullStr A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull
title_full_unstemmed A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull
title_short A 3.7 Mb Deletion Encompassing ZEB2 Causes a Novel Polled and Multisystemic Syndrome in the Progeny of a Somatic Mosaic Bull
title_sort 3.7 mb deletion encompassing zeb2 causes a novel polled and multisystemic syndrome in the progeny of a somatic mosaic bull
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494662/
https://www.ncbi.nlm.nih.gov/pubmed/23152852
http://dx.doi.org/10.1371/journal.pone.0049084
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