Morgagnian cataract resulting from a naturally occurring nonsense mutation elucidates a role of CPAMD8 in mammalian lens development

To investigate the genetic basis of hereditary lens opacities we analyzed 31 cases of bilateral congenital cataract in Red Holstein Friesian cattle. A genome-wide association study revealed a significant association on bovine chromosome 7 at positions 6,166,179 and 12,429,691. Whole genome re-sequen...

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Bibliographic Details
Published in:PloS one 2017-07, Vol.12 (7), p.e0180665-e0180665
Main Authors: Hollmann, Anne K, Dammann, Insa, Wemheuer, Wiebke M, Wemheuer, Wilhelm E, Chilla, Almuth, Tipold, Andrea, Schulz-Schaeffer, Walter J, Beck, Julia, Schütz, Ekkehard, Brenig, Bertram
Format: Article
Language:English
Subjects:
a2-Macroglobulin
alpha-Macroglobulins - physiology
Analysis
Animals
Beef cattle
Bioinformatics
Biology and Life Sciences
Cataract - genetics
Cataract - veterinary
Cataracts
Cattle
Chromosome 7
Chromosome Mapping
Codon, Nonsense
Codons
Congenital diseases
Epithelium
Eye
Eye lens
Female
Fetuses
Gene expression
Gene sequencing
Genes
Genetic aspects
Genetic disorders
Genome-wide association studies
Genomes
Genomics
Immunohistochemistry
Lens, Crystalline - growth & development
Lenses
Mammals
Medicine and Health Sciences
Mutation
Neuropathology
Nonsense mutation
Research and analysis methods
Ribonucleic acid
RNA
Stop codon
Veterinary medicine
α2-Macroglobulin
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Summary:To investigate the genetic basis of hereditary lens opacities we analyzed 31 cases of bilateral congenital cataract in Red Holstein Friesian cattle. A genome-wide association study revealed a significant association on bovine chromosome 7 at positions 6,166,179 and 12,429,691. Whole genome re-sequencing of one case and four relatives showed a nonsense mutation (g.5995966C>T) in the PZP-like, alpha-2-macroglobulin domain containing 8 (CPAMD8) gene leading to a premature stop codon (CPAMD8 p.Gln74*) associated with cataract development in cattle. With immunohistochemistry we confirmed a physiological expression of CPAMD8 in the ciliary body epithelium of the eye in unaffected cattle, while the protein was not detectable in the ciliary body of cattle with cataracts. RNA expression of CPAMD8 was detected in healthy adult, fetal and cataractous lenses.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0180665