Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.

Microphthalmia in sheep is an autosomal recessive inherited congenital anomaly found within the Texel breed. It is characterized by extremely small or absent eyes and affected lambs are absolutely blind. For the first time, we use a genome-wide ovine SNP array for positional cloning of a Mendelian t...

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Autores principales:	Doreen Becker, Jens Tetens, Adrian Brunner, Daniela Bürstel, Martin Ganter, James Kijas, International Sheep Genomics Consortium, Cord Drögemüller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b63a50765ed4d2f96e31250ad3fe78e
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spelling	oai:doaj.org-article:5b63a50765ed4d2f96e31250ad3fe78e2021-11-25T06:26:47ZMicrophthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.1932-620310.1371/journal.pone.0008689https://doaj.org/article/5b63a50765ed4d2f96e31250ad3fe78e2010-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20084168/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Microphthalmia in sheep is an autosomal recessive inherited congenital anomaly found within the Texel breed. It is characterized by extremely small or absent eyes and affected lambs are absolutely blind. For the first time, we use a genome-wide ovine SNP array for positional cloning of a Mendelian trait in sheep. Genotyping 23 cases and 23 controls using Illumina's OvineSNP50 BeadChip allowed us to localize the causative mutation for microphthalmia to a 2.4 Mb interval on sheep chromosome 22 by association and homozygosity mapping. The PITX3 gene is located within this interval and encodes a homeodomain-containing transcription factor involved in vertebrate lens formation. An abnormal development of the lens vesicle was shown to be the primary event in ovine microphthalmia. Therefore, we considered PITX3 a positional and functional candidate gene. An ovine BAC clone was sequenced, and after full-length cDNA cloning the PITX3 gene was annotated. Here we show that the ovine microphthalmia phenotype is perfectly associated with a missense mutation (c.338G>C, p.R113P) in the evolutionary conserved homeodomain of PITX3. Selection against this candidate causative mutation can now be used to eliminate microphthalmia from Texel sheep in production systems. Furthermore, the identification of a naturally occurring PITX3 mutation offers the opportunity to use the Texel as a genetically characterized large animal model for human microphthalmia.Doreen BeckerJens TetensAdrian BrunnerDaniela BürstelMartin GanterJames KijasInternational Sheep Genomics ConsortiumCord DrögemüllerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 1, p e8689 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Doreen Becker Jens Tetens Adrian Brunner Daniela Bürstel Martin Ganter James Kijas International Sheep Genomics Consortium Cord Drögemüller Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.
description	Microphthalmia in sheep is an autosomal recessive inherited congenital anomaly found within the Texel breed. It is characterized by extremely small or absent eyes and affected lambs are absolutely blind. For the first time, we use a genome-wide ovine SNP array for positional cloning of a Mendelian trait in sheep. Genotyping 23 cases and 23 controls using Illumina's OvineSNP50 BeadChip allowed us to localize the causative mutation for microphthalmia to a 2.4 Mb interval on sheep chromosome 22 by association and homozygosity mapping. The PITX3 gene is located within this interval and encodes a homeodomain-containing transcription factor involved in vertebrate lens formation. An abnormal development of the lens vesicle was shown to be the primary event in ovine microphthalmia. Therefore, we considered PITX3 a positional and functional candidate gene. An ovine BAC clone was sequenced, and after full-length cDNA cloning the PITX3 gene was annotated. Here we show that the ovine microphthalmia phenotype is perfectly associated with a missense mutation (c.338G>C, p.R113P) in the evolutionary conserved homeodomain of PITX3. Selection against this candidate causative mutation can now be used to eliminate microphthalmia from Texel sheep in production systems. Furthermore, the identification of a naturally occurring PITX3 mutation offers the opportunity to use the Texel as a genetically characterized large animal model for human microphthalmia.
format	article
author	Doreen Becker Jens Tetens Adrian Brunner Daniela Bürstel Martin Ganter James Kijas International Sheep Genomics Consortium Cord Drögemüller
author_facet	Doreen Becker Jens Tetens Adrian Brunner Daniela Bürstel Martin Ganter James Kijas International Sheep Genomics Consortium Cord Drögemüller
author_sort	Doreen Becker
title	Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.
title_short	Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.
title_full	Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.
title_fullStr	Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.
title_full_unstemmed	Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.
title_sort	microphthalmia in texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (pitx3) gene.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/5b63a50765ed4d2f96e31250ad3fe78e
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Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene.

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