Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.

<h4>Purpose</h4>Three related male English Cocker Spaniels (ECS) were reported to be congenitally blind. Examination of one of these revealed complete retinal detachment. A presumptive diagnosis of retinal dysplasia (RD) was provided and pedigree analysis was suggestive of an X-linked mo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hannah Joyce, Louise M Burmeister, Hattie Wright, Lorraine Fleming, James A C Oliver, Cathryn Mellersh
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/68f0e84fb78246afb814979f7bbeaf34
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:68f0e84fb78246afb814979f7bbeaf34
record_format	dspace
spelling	oai:doaj.org-article:68f0e84fb78246afb814979f7bbeaf342021-11-25T06:19:21ZIdentification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.1932-620310.1371/journal.pone.0251071https://doaj.org/article/68f0e84fb78246afb814979f7bbeaf342021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0251071https://doaj.org/toc/1932-6203<h4>Purpose</h4>Three related male English Cocker Spaniels (ECS) were reported to be congenitally blind. Examination of one of these revealed complete retinal detachment. A presumptive diagnosis of retinal dysplasia (RD) was provided and pedigree analysis was suggestive of an X-linked mode of inheritance. We sought to investigate the genetic basis of RD in this family of ECS.<h4>Methods</h4>Following whole genome sequencing (WGS) of the one remaining male RD-affected ECS, two distinct investigative approaches were employed: a candidate gene approach and a whole genome approach. In the candidate gene approach, COL9A2, COL9A3, NHEJ1, RS1 and NDP genes were investigated based on their known associations with RD and retinal detachment in dogs and humans. In the whole genome approach, affected WGS was compared with 814 unaffected canids to identify candidate variants, which were filtered based on appropriate segregation and predicted pathogenic effects followed by subsequent investigation of gene function. Candidate variants were tested for appropriate segregation in the ECS family and association with disease was assessed using samples from a total of 180 ECS.<h4>Results</h4>The same variant in NDP (c.653_654insC, p.Met114Hisfs*16) that was predicted to result in 15 aberrant amino acids before a premature stop in norrin protein, was identified independently by both approaches and was shown to segregate appropriately within the ECS family. Association of this variant with X-linked RD was significant (P = 0.0056).<h4>Conclusions</h4>For the first time, we report a variant associated with canine X-linked RD. NDP variants are already known to cause X-linked RD, along with other abnormalities, in human Norrie disease. Thus, the dog may serve as a useful large animal model for research.Hannah JoyceLouise M BurmeisterHattie WrightLorraine FlemingJames A C OliverCathryn MellershPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 5, p e0251071 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hannah Joyce Louise M Burmeister Hattie Wright Lorraine Fleming James A C Oliver Cathryn Mellersh Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.
description	<h4>Purpose</h4>Three related male English Cocker Spaniels (ECS) were reported to be congenitally blind. Examination of one of these revealed complete retinal detachment. A presumptive diagnosis of retinal dysplasia (RD) was provided and pedigree analysis was suggestive of an X-linked mode of inheritance. We sought to investigate the genetic basis of RD in this family of ECS.<h4>Methods</h4>Following whole genome sequencing (WGS) of the one remaining male RD-affected ECS, two distinct investigative approaches were employed: a candidate gene approach and a whole genome approach. In the candidate gene approach, COL9A2, COL9A3, NHEJ1, RS1 and NDP genes were investigated based on their known associations with RD and retinal detachment in dogs and humans. In the whole genome approach, affected WGS was compared with 814 unaffected canids to identify candidate variants, which were filtered based on appropriate segregation and predicted pathogenic effects followed by subsequent investigation of gene function. Candidate variants were tested for appropriate segregation in the ECS family and association with disease was assessed using samples from a total of 180 ECS.<h4>Results</h4>The same variant in NDP (c.653_654insC, p.Met114Hisfs*16) that was predicted to result in 15 aberrant amino acids before a premature stop in norrin protein, was identified independently by both approaches and was shown to segregate appropriately within the ECS family. Association of this variant with X-linked RD was significant (P = 0.0056).<h4>Conclusions</h4>For the first time, we report a variant associated with canine X-linked RD. NDP variants are already known to cause X-linked RD, along with other abnormalities, in human Norrie disease. Thus, the dog may serve as a useful large animal model for research.
format	article
author	Hannah Joyce Louise M Burmeister Hattie Wright Lorraine Fleming James A C Oliver Cathryn Mellersh
author_facet	Hannah Joyce Louise M Burmeister Hattie Wright Lorraine Fleming James A C Oliver Cathryn Mellersh
author_sort	Hannah Joyce
title	Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.
title_short	Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.
title_full	Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.
title_fullStr	Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.
title_full_unstemmed	Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.
title_sort	identification of a variant in ndp associated with x-linked retinal dysplasia in the english cocker spaniel dog.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/68f0e84fb78246afb814979f7bbeaf34
work_keys_str_mv	AT hannahjoyce identificationofavariantinndpassociatedwithxlinkedretinaldysplasiaintheenglishcockerspanieldog AT louisemburmeister identificationofavariantinndpassociatedwithxlinkedretinaldysplasiaintheenglishcockerspanieldog AT hattiewright identificationofavariantinndpassociatedwithxlinkedretinaldysplasiaintheenglishcockerspanieldog AT lorrainefleming identificationofavariantinndpassociatedwithxlinkedretinaldysplasiaintheenglishcockerspanieldog AT jamesacoliver identificationofavariantinndpassociatedwithxlinkedretinaldysplasiaintheenglishcockerspanieldog AT cathrynmellersh identificationofavariantinndpassociatedwithxlinkedretinaldysplasiaintheenglishcockerspanieldog
_version_	1718413867080482816

Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.

Ejemplares similares