由自然发生的无义突变导致的莫尔加尼白内障阐明了CPAMD8在哺乳动物晶状体发育中的作用。
Morgagnian cataract resulting from a naturally occurring nonsense mutation elucidates a role of CPAMD8 in mammalian lens development.
作者信息
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
机构信息
University of Goettingen, Institute of Veterinary Medicine, Goettingen, Germany.
University Medical Center Goettingen, Department of Neuropathology, Prion and Dementia Research Unit, Goettingen, Germany.
出版信息
PLoS One. 2017 Jul 6;12(7):e0180665. doi: 10.1371/journal.pone.0180665. eCollection 2017.
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.
为了研究遗传性晶状体混浊的遗传基础，我们分析了31例红荷斯坦弗里生牛的双侧先天性白内障病例。全基因组关联研究揭示了在牛7号染色体上6,166,179和12,429,691位置存在显著关联。对1例病例及其4个亲属进行全基因组重测序，结果显示在含PZP样α-2-巨球蛋白结构域8（CPAMD8）基因中存在一个无义突变（g.5995966C>T），导致提前终止密码子（CPAMD8 p.Gln74*），这与牛的白内障发生有关。通过免疫组织化学，我们证实CPAMD8在未受影响牛的眼睫状体上皮中有生理性表达，而在患白内障牛的睫状体中未检测到该蛋白。在健康成年、胎儿和白内障晶状体中均检测到CPAMD8的RNA表达。
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