<i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle

Sporadic occurrence of inherited eye disorders has been reported in cattle but so far pathogenic variants were found only for rare forms of cataract but not for retinopathies. The aim of this study was to characterize the phenotype and the genetic aetiology of a recessive form of congenital day-blin...

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Autores principales:	Irene M. Häfliger, Emma Marchionatti, Michele Stengård, Sonja Wolf-Hofstetter, Julia M. Paris, Joana G. P. Jacinto, Christine Watté, Katrin Voelter, Laurence M. Occelli, András M. Komáromy, Anna Oevermann, Christine Goepfert, Angelica Borgo, Raphaël Roduit, Mirjam Spengeler, Franz R. Seefried, Cord Drögemüller
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Bos taurus</i> animal model day-blindness retina development mendelian genetics Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/4cbbfd0ed9054484b355f5c1b84aa098
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spelling	oai:doaj.org-article:4cbbfd0ed9054484b355f5c1b84aa0982021-11-25T17:56:41Z<i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle10.3390/ijms2222124401422-00671661-6596https://doaj.org/article/4cbbfd0ed9054484b355f5c1b84aa0982021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12440https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Sporadic occurrence of inherited eye disorders has been reported in cattle but so far pathogenic variants were found only for rare forms of cataract but not for retinopathies. The aim of this study was to characterize the phenotype and the genetic aetiology of a recessive form of congenital day-blindness observed in several cases of purebred Original Braunvieh cattle. Electroretinography in an affected calf revealed absent cone-mediated function, whereas the rods continue to function normally. Brain areas involved in vision were morphologically normal. When targeting cones by immunofluorescence, a decrease in cone number and an accumulation of beta subunits of cone cyclic-nucleotide gated channel (CNGB3) in the outer plexiform layer of affected animals was obvious. Achromatopsia is a monogenic Mendelian disease characterized by the loss of cone photoreceptor function resulting in day-blindness, total color-blindness, and decreased central visual acuity. After SNP genotyping and subsequent homozygosity mapping with twelve affected cattle, we performed whole-genome sequencing and variant calling of three cases. We identified a single missense variant in the bovine <i>CNGB3</i> gene situated in a ~2.5 Mb homozygous genome region on chromosome 14 shared between all cases. All affected cattle were homozygous carriers of the p.Asp251Asn mutation that was predicted to be deleterious, affecting an evolutionary conserved residue. In conclusion, we have evidence for the occurrence of a breed-specific novel <i>CNGB3</i>-related form of recessively inherited achromatopsia in Original Braunvieh cattle which we have designated OH1 showing an allele frequency of the deleterious allele of ~8%. The identification of carriers will enable selection against this inherited disorder. The studied cattle might serve as an animal model to further elucidate the function of <i>CNGB3</i> in mammals.Irene M. HäfligerEmma MarchionattiMichele StengårdSonja Wolf-HofstetterJulia M. ParisJoana G. P. JacintoChristine WattéKatrin VoelterLaurence M. OccelliAndrás M. KomáromyAnna OevermannChristine GoepfertAngelica BorgoRaphaël RoduitMirjam SpengelerFranz R. SeefriedCord DrögemüllerMDPI AGarticle<i>Bos taurus</i>animal modelday-blindnessretinadevelopmentmendelian geneticsBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12440, p 12440 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Bos taurus</i> animal model day-blindness retina development mendelian genetics Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	<i>Bos taurus</i> animal model day-blindness retina development mendelian genetics Biology (General) QH301-705.5 Chemistry QD1-999 Irene M. Häfliger Emma Marchionatti Michele Stengård Sonja Wolf-Hofstetter Julia M. Paris Joana G. P. Jacinto Christine Watté Katrin Voelter Laurence M. Occelli András M. Komáromy Anna Oevermann Christine Goepfert Angelica Borgo Raphaël Roduit Mirjam Spengeler Franz R. Seefried Cord Drögemüller <i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle
description	Sporadic occurrence of inherited eye disorders has been reported in cattle but so far pathogenic variants were found only for rare forms of cataract but not for retinopathies. The aim of this study was to characterize the phenotype and the genetic aetiology of a recessive form of congenital day-blindness observed in several cases of purebred Original Braunvieh cattle. Electroretinography in an affected calf revealed absent cone-mediated function, whereas the rods continue to function normally. Brain areas involved in vision were morphologically normal. When targeting cones by immunofluorescence, a decrease in cone number and an accumulation of beta subunits of cone cyclic-nucleotide gated channel (CNGB3) in the outer plexiform layer of affected animals was obvious. Achromatopsia is a monogenic Mendelian disease characterized by the loss of cone photoreceptor function resulting in day-blindness, total color-blindness, and decreased central visual acuity. After SNP genotyping and subsequent homozygosity mapping with twelve affected cattle, we performed whole-genome sequencing and variant calling of three cases. We identified a single missense variant in the bovine <i>CNGB3</i> gene situated in a ~2.5 Mb homozygous genome region on chromosome 14 shared between all cases. All affected cattle were homozygous carriers of the p.Asp251Asn mutation that was predicted to be deleterious, affecting an evolutionary conserved residue. In conclusion, we have evidence for the occurrence of a breed-specific novel <i>CNGB3</i>-related form of recessively inherited achromatopsia in Original Braunvieh cattle which we have designated OH1 showing an allele frequency of the deleterious allele of ~8%. The identification of carriers will enable selection against this inherited disorder. The studied cattle might serve as an animal model to further elucidate the function of <i>CNGB3</i> in mammals.
format	article
author	Irene M. Häfliger Emma Marchionatti Michele Stengård Sonja Wolf-Hofstetter Julia M. Paris Joana G. P. Jacinto Christine Watté Katrin Voelter Laurence M. Occelli András M. Komáromy Anna Oevermann Christine Goepfert Angelica Borgo Raphaël Roduit Mirjam Spengeler Franz R. Seefried Cord Drögemüller
author_facet	Irene M. Häfliger Emma Marchionatti Michele Stengård Sonja Wolf-Hofstetter Julia M. Paris Joana G. P. Jacinto Christine Watté Katrin Voelter Laurence M. Occelli András M. Komáromy Anna Oevermann Christine Goepfert Angelica Borgo Raphaël Roduit Mirjam Spengeler Franz R. Seefried Cord Drögemüller
author_sort	Irene M. Häfliger
title	<i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle
title_short	<i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle
title_full	<i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle
title_fullStr	<i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle
title_full_unstemmed	<i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle
title_sort	<i>cngb3</i> missense variant causes recessive achromatopsia in original braunvieh cattle
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4cbbfd0ed9054484b355f5c1b84aa098
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<i>CNGB3</i> Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle

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