{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:43:41Z","timestamp":1784123021685,"version":"3.55.0"},"reference-count":30,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:00:00Z","timestamp":1637193600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["31003A_172911"],"award-info":[{"award-number":["31003A_172911"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms222212440","type":"journal-article","created":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T08:53:56Z","timestamp":1637225636000},"page":"12440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["CNGB3 Missense Variant Causes Recessive Achromatopsia in Original Braunvieh Cattle"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5648-963X","authenticated-orcid":false,"given":"Irene M.","family":"H\u00e4fliger","sequence":"first","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9113-5829","authenticated-orcid":false,"given":"Emma","family":"Marchionatti","sequence":"additional","affiliation":[{"name":"Clinic for Ruminants, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Steng\u00e5rd","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, L\u00e4nggassstrasse 128, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Wolf-Hofstetter","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia M.","family":"Paris","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6438-7975","authenticated-orcid":false,"given":"Joana G. P.","family":"Jacinto","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medical Sciences, University of Bologna, 50 Ozzano Emilia, 40064 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Watt\u00e9","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, L\u00e4nggassstrasse 128, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6349-6782","authenticated-orcid":false,"given":"Katrin","family":"Voelter","sequence":"additional","affiliation":[{"name":"Ophthalmology Section, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1568-4527","authenticated-orcid":false,"given":"Laurence M.","family":"Occelli","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Michigan State University, 736 Wilson Rd., East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e1s M.","family":"Kom\u00e1romy","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Michigan State University, 736 Wilson Rd., East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3569-8547","authenticated-orcid":false,"given":"Anna","family":"Oevermann","sequence":"additional","affiliation":[{"name":"Division of Neurological Sciences, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Goepfert","sequence":"additional","affiliation":[{"name":"COMPATH, Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, L\u00e4nggassstrasse 122, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelica","family":"Borgo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Av. de France 15, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7440-2799","authenticated-orcid":false,"given":"Rapha\u00ebl","family":"Roduit","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Lausanne, Jules-Gonin Eye Hospital, Av. de France 15, 1004 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Spengeler","sequence":"additional","affiliation":[{"name":"Qualitas AG, Chamerstrasse 56, 6300 Zug, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4396-2747","authenticated-orcid":false,"given":"Franz R.","family":"Seefried","sequence":"additional","affiliation":[{"name":"Qualitas AG, Chamerstrasse 56, 6300 Zug, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-522X","authenticated-orcid":false,"given":"Cord","family":"Dr\u00f6gem\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,18]]},"reference":[{"key":"ref_1","unstructured":"Lavach, J.D. (1990). Large Animal Ophthalmology, Mosby."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"xi","DOI":"10.1016\/j.cvfa.2010.09.005","article-title":"Production animal ophthalmology","volume":"26","author":"Williams","year":"2010","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.cvfa.2010.08.005","article-title":"Welfare issues in farm animal ophthalmology","volume":"26","author":"Williams","year":"2010","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_4","first-page":"577","article-title":"Congenital ocular defects in food-producing animals","volume":"6","author":"Leipold","year":"1984","journal-title":"Vet. Clin. N. Am. Large Anim. Pract."},{"key":"ref_5","unstructured":"Gelatt, K.N., Ben-Shlomo, G., Gilger, B.C., Hendrix, D.V., Kern, T.J., and Plummer, C.E. (2021). Veterinary Ophthalmology, John Wiley & Sons. [6th ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.cvfa.2010.09.001","article-title":"Congenital abnormalities in production animals","volume":"26","author":"Williams","year":"2010","journal-title":"Vet. Clin. N. Am. Food Anim. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"He, X., Li, Y., Li, M., Jia, G., Dong, H., Zhang, Y., He, C., Wang, C., Deng, L., and Yang, Y. (2012). Hypovitaminosis A coupled to secondary bacterial infection in beef cattle. BMC Vet. Res., 8.","DOI":"10.1186\/1746-6148-8-222"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Murgiano, L., Jagannathan, V., Calderoni, V., Joechler, M., Gentile, A., and Dr\u00f6gem\u00fcller, C. (2014). Looking the cow in the eye: Deletion in the NID1 gene is associated with recessive inherited cataract in Romagnola cattle. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110628"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hollmann, A.K., Dammann, I., Wemheuer, W.M., Wemheuer, W.E., Chilla, A., Tipold, A., Schulz-Schaeffer, W.J., Beck, J., Sch\u00fctz, E., and Brenig, B. (2017). Morgagnian cataract resulting from a naturally occurring nonsense mutation elucidates a role of CPAMD8 in mammalian lens development. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180665"},{"key":"ref_10","first-page":"588","article-title":"Genotypes and phenotypes of genes associated with achromatopsia: A reference for clinical genetic testing","volume":"26","author":"Sun","year":"2020","journal-title":"Mol. Vis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ygeno.2009.10.003","article-title":"A mutation in gene CNGA3 is associated with day blindness in sheep","volume":"95","author":"Reicher","year":"2010","journal-title":"Genomics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19314","DOI":"10.1038\/s41598-020-76205-z","article-title":"Naturally-occurring myopia and loss of cone function in a sheep model of achromatopsia","volume":"10","author":"Ross","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.tvjl.2009.07.007","article-title":"Day blind sheep and the importance of large animal disease models","volume":"185","year":"2010","journal-title":"Vet. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Winkler, P.A., Occelli, L.M., and Petersen-Jones, S.M. (2020). Large animal models of inherited retinal degenerations: A review. Cells, 9.","DOI":"10.3390\/cells9040882"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rothammer, S., Seichter, D., F\u00f6rster, M., and Medugorac, I. (2013). A genome-wide scan for signatures of differential artificial selection in ten cattle breeds. BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-908"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s12711-017-0358-6","article-title":"Population structure and genomic inbreeding in nine Swiss dairy cattle populations","volume":"49","author":"Burren","year":"2017","journal-title":"Genet. Sel. Evol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bhati, M., Kadri, N.K., Crysnanto, D., and Pausch, H. (2020). Assessing genomic diversity and signatures of selection in Original Braunvieh cattle using whole-genome sequencing data. BMC Genom., 21.","DOI":"10.1186\/s12864-020-6446-y"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1093\/bioinformatics\/btv195","article-title":"PROVEAN web server: A tool to predict the functional effect of amino acid substitutions and indels","volume":"31","author":"Choi","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s00335-011-9361-3","article-title":"Genetic and phenotypic variations of inherited retinal diseases in dogs: The power of within- and across-breed studies","volume":"23","author":"Miyadera","year":"2012","journal-title":"Mamm. Genome"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Yeh, C.Y., Goldstein, O., Kukekova, A.V., Holley, D., Knollinger, A.M., Huson, H.J., Pearce-Kelling, S.E., Acland, G.M., and Kom\u00e1romy, A.M. (2013). Genomic deletion of CNGB3 is identical by descent in multiple canine breeds and causes achromatopsia. BMC Genet., 14.","DOI":"10.1186\/1471-2156-14-27"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tanaka, N., Delemotte, L., Klein, M.L., Kom\u00e1romy, A.M., and Tanaka, J.C. (2014). A cyclic nucleotide-gated channel mutation associated with canine daylight blindness provides insight into a role for the S2 segment tri-Asp motif in channel biogenesis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0088768"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Tanaka, N., Dutrow, E.V., Miyadera, K., Delemotte, L., MacDermaid, C.M., Reinstein, S.L., Crumley, W.R., Dixon, C.J., Casal, M.L., and Klein, M.L. (2015). Canine CNGA3 Gene Mutations Provide Novel Insights into Human Achromatopsia-Associated Channelopathies and Treatment. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0138943"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1093\/hmg\/11.16.1823","article-title":"Canine CNGB3 mutations establish cone degeneration as orthologous to the human achromatopsia locus ACHM3","volume":"11","author":"Sidjanin","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_24","first-page":"910","article-title":"Achromatopsia caused by novel missense mutations in the CNGA3 gene","volume":"8","author":"Chen","year":"2015","journal-title":"Int. J. Ophthalmol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1439-0388.2005.00552.x","article-title":"Estimates of genetic diversity in the brown cattle population of Switzerland obtained from pedigree information","volume":"122","author":"Hagger","year":"2005","journal-title":"J. Anim. Breed. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","first-page":"421","article-title":"FImpute\u2014An efficient imputa- tion algorithm for dairy cattle populations","volume":"94","author":"Sargolzaei","year":"2011","journal-title":"J. Dairy Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/age.12923","article-title":"Identification of small and large genomic candidate variants in bovine pulmonary hypoplasia and anasarca syndrome","volume":"51","author":"Wiedemar","year":"2020","journal-title":"Anim. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev-animal-020518-115024","article-title":"1000 Bull Genomes Project to Map Simple and Complex Genetic Traits in Cattle: Applications and Outcomes","volume":"7","author":"Hayes","year":"2019","journal-title":"Annu. Rev. Anim. Biosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12440\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:32:12Z","timestamp":1760167932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,18]]},"references-count":30,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222212440"],"URL":"https:\/\/doi.org\/10.3390\/ijms222212440","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,18]]}}}