1. CNGB3 Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle.
- Author
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Häfliger IM, Marchionatti E, Stengård M, Wolf-Hofstetter S, Paris JM, Jacinto JGP, Watté C, Voelter K, Occelli LM, Komáromy AM, Oevermann A, Goepfert C, Borgo A, Roduit R, Spengeler M, Seefried FR, and Drögemüller C
- Subjects
- Amino Acid Substitution, Animals, Asparagine metabolism, Aspartic Acid metabolism, Cattle, Color Vision Defects diagnostic imaging, Color Vision Defects metabolism, Color Vision Defects pathology, Cyclic Nucleotide-Gated Cation Channels deficiency, Electroretinography, Female, Gene Expression, Gene Frequency, Homozygote, Male, Phenotype, Protein Subunits deficiency, Retinal Cone Photoreceptor Cells pathology, Retinal Rod Photoreceptor Cells cytology, Retinal Rod Photoreceptor Cells metabolism, Whole Genome Sequencing, Alleles, Color Vision Defects genetics, Cyclic Nucleotide-Gated Cation Channels genetics, Mutation, Missense, Protein Subunits genetics, Retinal Cone Photoreceptor Cells metabolism
- Abstract
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 CNGB3 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 CNGB3 -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 CNGB3 in mammals.
- Published
- 2021
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