CNGB3 Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle

Autor: 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
Přispěvatelé: Häfliger, Irene M., Marchionatti, Emma, Stengård, Michele, Wolf-Hofstetter, Sonja, Paris, Julia M., Jacinto, Joana G. P., Watté, Christine, Voelter, Katrin, Occelli, Laurence M., Komáromy, András M., Oevermann, Anna, Goepfert, Christine, Borgo, Angelica, Roduit, Raphaël, Spengeler, Mirjam, Seefried, Franz R., Drögemüller, Cord
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 22
International journal of molecular sciences, vol. 22, no. 22, pp. 12440
Häfliger, Irene M.; Marchionatti, Emma; Stengard, Michele; Wolf-Hofstetter, Sonja; Paris, Julia M.; Jacinto, Joana G. P.; Watté, Christine; Voelter, Katrin; Occelli, Laurence M.; Komáromy, András M.; Oevermann, Anna; Goepfert, Christine; Borgo, Angelica; Roduit, Raphaël; Spengeler, Mirjam; Seefried, Franz R.; Drögemüller, Cord (2021). CNGB3 Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle. International journal of molecular sciences, 22(22), p. 12440. MDPI 10.3390/ijms222212440
International Journal of Molecular Sciences, Vol 22, Iss 12440, p 12440 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms222212440
Popis: 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.
Databáze: OpenAIRE
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