Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep

[EN] Lissencephaly is an inherited developmental disorder in which neuronal migration is impaired. A type of lissencephaly associated with cerebellar hypoplasia (LCH) was diagnosed in a commercial flock of Spanish Churra sheep. The genotyping of 7 affected animals and 33 controls with the OvineSNP50...

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Authors: Suárez Vega, Aroa, Gutiérrez Gil, Beatriz, Cuchillo Ibáñez, Inmaculada, Sáez Valero, Javier, Pérez Pérez, Valentín, García Gámez, Elsa, Benavides Silván, Julio, Arranz Santos, Juan José
Format: article
Status:Published version
Publication Date:2013
Country:España
Institution:Universidad de León
Repository:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/24705
Online Access:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081072
https://hdl.handle.net/10612/24705
Access Level:Open access
Keyword:Genética
Producción animal
Veterinaria
31-bp
Cerebellar hypoplasia
RELN
Sheep
3109 Ciencias Veterinarias
3104 Producción Animal
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spelling Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in SheepSuárez Vega, AroaGutiérrez Gil, BeatrizCuchillo Ibáñez, InmaculadaSáez Valero, JavierPérez Pérez, ValentínGarcía Gámez, ElsaBenavides Silván, JulioArranz Santos, Juan JoséGenéticaProducción animalVeterinaria31-bpCerebellar hypoplasiaRELNSheep3109 Ciencias Veterinarias3104 Producción Animal[EN] Lissencephaly is an inherited developmental disorder in which neuronal migration is impaired. A type of lissencephaly associated with cerebellar hypoplasia (LCH) was diagnosed in a commercial flock of Spanish Churra sheep. The genotyping of 7 affected animals and 33 controls with the OvineSNP50 BeadChip enabled the localization of the causative mutation for ovine LCH to a 4.8-Mb interval on sheep chromosome 4 using genome-wide association and homozygosity mapping. The RELN gene, which is located within this interval, was considered a strong positional and functional candidate because it plays critical roles in neuronal migration and layer formation. By performing a sequencing analysis of this gene's specific mRNA in a control lamb, we obtained the complete CDS of the ovine RELN gene. The cDNA sequence from an LCH-affected lamb revealed a deletion of 31 bp (c.5410-5440del) in predicted exon 36 of RELN, resulting in a premature termination codon. A functional analysis of this mutation revealed decreased levels of RELN mRNA and a lack of reelin protein in the brain cortex and blood of affected lambs. This mutation showed a complete concordance with the Mendelian recessive pattern of inheritance observed for the disease. The identification of the causal mutation of LCH in Churra sheep will facilitate the implementation of gene-assisted selection to detect heterozygous mutants, which will help breeders avoid at-risk matings in their flocks. Moreover, the identification of this naturally occurring RELN mutation provides an opportunity to use Churra sheep as a genetically characterized large animal model for the study of reelin functions in the developing and mature brainSIThis work was supported by the Spanish Ministry of Science (Project AGL2009-07000) and by the European Commission 3SR Project (Sustainable Solutions for Small Ruminants; http://www.3srbreeding.eu) (to JJA). Fondo de Investigaciones Sanitarias (PS09/00684; PI12/00593), Fundación Ramón Areces, and CIBERNED, Instituto de Salud Carlos III from Spain (to JSV). Aroa Suarez-Vega is funded by an FPU contract from the Spanish Ministry of Education. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPublic Library of ScienceProducción AnimalFacultad de Veterinaria2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081072https://hdl.handle.net/10612/24705reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Universidad de LeónInglésinfo:eu-repo/grantAgreement/MICINN/Programa Nacional de Investigación Fundamental/AGL2009-07000info:eu-repo/grantAgreement/MICINN/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/PS09info:eu-repo/grantAgreement/MINECO/Acción Estratégica de Salud/ PI12http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:buleria.unileon.es:10612/247052026-06-24T12:43:27Z
dc.title.none.fl_str_mv Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep
title Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep
spellingShingle Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep
Suárez Vega, Aroa
Genética
Producción animal
Veterinaria
31-bp
Cerebellar hypoplasia
RELN
Sheep
3109 Ciencias Veterinarias
3104 Producción Animal
title_short Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep
title_full Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep
title_fullStr Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep
title_full_unstemmed Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep
title_sort Identification of a 31-bp Deletion in the RELN Gene Causing Lissencephaly with Cerebellar Hypoplasia in Sheep
dc.creator.none.fl_str_mv Suárez Vega, Aroa
Gutiérrez Gil, Beatriz
Cuchillo Ibáñez, Inmaculada
Sáez Valero, Javier
Pérez Pérez, Valentín
García Gámez, Elsa
Benavides Silván, Julio
Arranz Santos, Juan José
author Suárez Vega, Aroa
author_facet Suárez Vega, Aroa
Gutiérrez Gil, Beatriz
Cuchillo Ibáñez, Inmaculada
Sáez Valero, Javier
Pérez Pérez, Valentín
García Gámez, Elsa
Benavides Silván, Julio
Arranz Santos, Juan José
author_role author
author2 Gutiérrez Gil, Beatriz
Cuchillo Ibáñez, Inmaculada
Sáez Valero, Javier
Pérez Pérez, Valentín
García Gámez, Elsa
Benavides Silván, Julio
Arranz Santos, Juan José
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Producción Animal
Facultad de Veterinaria
dc.subject.none.fl_str_mv Genética
Producción animal
Veterinaria
31-bp
Cerebellar hypoplasia
RELN
Sheep
3109 Ciencias Veterinarias
3104 Producción Animal
topic Genética
Producción animal
Veterinaria
31-bp
Cerebellar hypoplasia
RELN
Sheep
3109 Ciencias Veterinarias
3104 Producción Animal
description [EN] Lissencephaly is an inherited developmental disorder in which neuronal migration is impaired. A type of lissencephaly associated with cerebellar hypoplasia (LCH) was diagnosed in a commercial flock of Spanish Churra sheep. The genotyping of 7 affected animals and 33 controls with the OvineSNP50 BeadChip enabled the localization of the causative mutation for ovine LCH to a 4.8-Mb interval on sheep chromosome 4 using genome-wide association and homozygosity mapping. The RELN gene, which is located within this interval, was considered a strong positional and functional candidate because it plays critical roles in neuronal migration and layer formation. By performing a sequencing analysis of this gene's specific mRNA in a control lamb, we obtained the complete CDS of the ovine RELN gene. The cDNA sequence from an LCH-affected lamb revealed a deletion of 31 bp (c.5410-5440del) in predicted exon 36 of RELN, resulting in a premature termination codon. A functional analysis of this mutation revealed decreased levels of RELN mRNA and a lack of reelin protein in the brain cortex and blood of affected lambs. This mutation showed a complete concordance with the Mendelian recessive pattern of inheritance observed for the disease. The identification of the causal mutation of LCH in Churra sheep will facilitate the implementation of gene-assisted selection to detect heterozygous mutants, which will help breeders avoid at-risk matings in their flocks. Moreover, the identification of this naturally occurring RELN mutation provides an opportunity to use Churra sheep as a genetically characterized large animal model for the study of reelin functions in the developing and mature brain
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081072
https://hdl.handle.net/10612/24705
url https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081072
https://hdl.handle.net/10612/24705
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MICINN/Programa Nacional de Investigación Fundamental/AGL2009-07000
info:eu-repo/grantAgreement/MICINN/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/PS09
info:eu-repo/grantAgreement/MINECO/Acción Estratégica de Salud/ PI12
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:BULERIA. Repositorio Institucional de la Universidad de León
instname:Universidad de León
instname_str Universidad de León
reponame_str BULERIA. Repositorio Institucional de la Universidad de León
collection BULERIA. Repositorio Institucional de la Universidad de León
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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