MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA)
We investigated a hereditary syndrome in Cane Corso dogs. Affected dogs developed dental-skeletal-retinal anomaly (DSRA), clinically characterized by brittle, discolored, translucent teeth, disproportionate growth and progressive retinal degeneration resulting in vision loss. Combined linkage and ho...
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ftunivutrecht:oai:dspace.library.uu.nl:1874/415846 2023-11-12T04:15:40+01:00 MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) Christen, Matthias Booij-Vrieling, Henriëtte Oksa-Minalto, Jelena de Vries, Cynthia Kehl, Alexandra Jagannathan, Vidhya Leeb, Tosso Chirurgie dCSCA AVR 2021-10 application/pdf https://dspace.library.uu.nl/handle/1874/415846 en eng 2073-4425 https://dspace.library.uu.nl/handle/1874/415846 info:eu-repo/semantics/OpenAccess Animal model Canis lupus familiaris Collagen Endoplasmic reticulum Non-coding Precision medicine Splicing TANGO1 Genetics Genetics(clinical) Article 2021 ftunivutrecht 2023-11-01T23:27:31Z We investigated a hereditary syndrome in Cane Corso dogs. Affected dogs developed dental-skeletal-retinal anomaly (DSRA), clinically characterized by brittle, discolored, translucent teeth, disproportionate growth and progressive retinal degeneration resulting in vision loss. Combined linkage and homozygosity mapping delineated a 5.8 Mb critical interval. The comparison of whole genome sequence data of an affected dog to 789 control genomes revealed a private homozygous splice region variant in the critical interval. It affected the MIA3 gene encoding the MIA SH3 domain ER export factor 3, which has an essential role in the export of collagen and other secreted proteins. The identified variant, XM_005640835.3:c.3822+3_3822+4del, leads to skipping of two exons from the wild type transcript, XM_005640835.3:r.3712_3822del. Genotypes at the variant were consistent with monogenic autosomal recessive mode of inheritance in a complete family and showed perfect genotype-phenotype association in 18 affected and 22 unaffected Cane Corso dogs. MIA3 variants had previously been shown to cause related phenotypes in humans and mice. Our data in dogs together with the existing functional knowledge of MIA3 variants in other mammalian species suggest the MIA3 splice defect and a near complete loss of gene function as causative molecular pathomechanism for the DSRA phenotype in the investigated dogs. Article in Journal/Newspaper Canis lupus Utrecht University Repository |
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Open Polar |
collection |
Utrecht University Repository |
op_collection_id |
ftunivutrecht |
language |
English |
topic |
Animal model Canis lupus familiaris Collagen Endoplasmic reticulum Non-coding Precision medicine Splicing TANGO1 Genetics Genetics(clinical) |
spellingShingle |
Animal model Canis lupus familiaris Collagen Endoplasmic reticulum Non-coding Precision medicine Splicing TANGO1 Genetics Genetics(clinical) Christen, Matthias Booij-Vrieling, Henriëtte Oksa-Minalto, Jelena de Vries, Cynthia Kehl, Alexandra Jagannathan, Vidhya Leeb, Tosso MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
topic_facet |
Animal model Canis lupus familiaris Collagen Endoplasmic reticulum Non-coding Precision medicine Splicing TANGO1 Genetics Genetics(clinical) |
description |
We investigated a hereditary syndrome in Cane Corso dogs. Affected dogs developed dental-skeletal-retinal anomaly (DSRA), clinically characterized by brittle, discolored, translucent teeth, disproportionate growth and progressive retinal degeneration resulting in vision loss. Combined linkage and homozygosity mapping delineated a 5.8 Mb critical interval. The comparison of whole genome sequence data of an affected dog to 789 control genomes revealed a private homozygous splice region variant in the critical interval. It affected the MIA3 gene encoding the MIA SH3 domain ER export factor 3, which has an essential role in the export of collagen and other secreted proteins. The identified variant, XM_005640835.3:c.3822+3_3822+4del, leads to skipping of two exons from the wild type transcript, XM_005640835.3:r.3712_3822del. Genotypes at the variant were consistent with monogenic autosomal recessive mode of inheritance in a complete family and showed perfect genotype-phenotype association in 18 affected and 22 unaffected Cane Corso dogs. MIA3 variants had previously been shown to cause related phenotypes in humans and mice. Our data in dogs together with the existing functional knowledge of MIA3 variants in other mammalian species suggest the MIA3 splice defect and a near complete loss of gene function as causative molecular pathomechanism for the DSRA phenotype in the investigated dogs. |
author2 |
Chirurgie dCSCA AVR |
format |
Article in Journal/Newspaper |
author |
Christen, Matthias Booij-Vrieling, Henriëtte Oksa-Minalto, Jelena de Vries, Cynthia Kehl, Alexandra Jagannathan, Vidhya Leeb, Tosso |
author_facet |
Christen, Matthias Booij-Vrieling, Henriëtte Oksa-Minalto, Jelena de Vries, Cynthia Kehl, Alexandra Jagannathan, Vidhya Leeb, Tosso |
author_sort |
Christen, Matthias |
title |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_short |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_full |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_fullStr |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_full_unstemmed |
MIA3 Splice Defect in Cane Corso Dogs with Dental-Skeletal-Retinal Anomaly (DSRA) |
title_sort |
mia3 splice defect in cane corso dogs with dental-skeletal-retinal anomaly (dsra) |
publishDate |
2021 |
url |
https://dspace.library.uu.nl/handle/1874/415846 |
genre |
Canis lupus |
genre_facet |
Canis lupus |
op_relation |
2073-4425 https://dspace.library.uu.nl/handle/1874/415846 |
op_rights |
info:eu-repo/semantics/OpenAccess |
_version_ |
1782332954591100928 |