title: Looking the cow in the eye: deletion in the NID1 gene is associated with recessive inherited cataract in Romagnola cattle.
abstract: Cataract is a known condition leading to opacification of the eye lens causing partial or total blindness. Mutations are known to cause autosomal dominant or recessive inherited forms of cataracts in humans, mice, rats, guinea pigs and dogs. The use of large-sized animal models instead of those using mice for the study of this condition has been discussed due to the small size of rodent lenses. Four juvenile-onset cases of bilateral incomplete immature nuclear cataract were recently observed in Romagnola cattle. Pedigree analysis suggested a monogenic autosomal recessive inheritance. In addition to the cataract, one of the cases displayed abnormal head movements. Genome-wide association and homozygosity mapping and subsequent whole genome sequencing of a single case identified two perfectly associated sequence variants in a critical interval of 7.2 Mb on cattle chromosome 28: a missense point mutation located in an uncharacterized locus and an 855 bp deletion across the exon 19/intron 19 border of the bovine nidogen 1 (NID1) gene (c.3579_3604+829del). RT-PCR showed that NID1 is expressed in bovine lenses while the transcript of the second locus was absent. The NID1 deletion leads to the skipping of exon 19 during transcription and is therefore predicted to cause a frameshift and premature stop codon (p.1164fs27X). The truncated protein lacks a C-terminal domain essential for binding with matrix assembly complexes. Nidogen 1 deficient mice show neurological abnormalities and highly irregular crystal lens alterations. This study adds NID1 to the list of candidate genes for inherited cataract in humans and is the first report of a naturally occurring mutation leading to non-syndromic catarct in cattle provides a potential large animal model for human cataract.
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Murgiano
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Jagannathan
authors.affiliation: Bovine practitioner, Fontanelice, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Calderoni
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: Monika
authors.initials: M
authors.lastname: Joechler
authors.affiliation: Department of Veterinary Medical Sciences, University of Bologna, Ozzano dell'Emilia, Italy.
authors.forename: Arcangelo
authors.initials: A
authors.lastname: Gentile
authors.affiliation: Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Cord
authors.initials: C
authors.lastname: Drögemüller
mesh_terms: D000818:Animals; D001947:Breeding; D002386:Cataract / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D017353:Gene Deletion; D005808:Genes, Recessive; D056726:Genetic Association Studies; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D008562:Membrane Glycoproteins; C029967:nidogen