Searching for New Genes That Cause Usher Syndrome.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Moshiri Ala, Kasiri Niusha, Shea Michael, Ali Layla, Yang Benjamin, Shao Andy, Clary Dave, Flenniken Ann M, Eskandarian Mohammad, Amarie Oana V, Becker Lore, Sangermano Riccardo, Place Emily M, Bujakowska Kinga M, Huckfeldt Rachel M, Berberovic Zorana, Bour Raphaël, Riet Fabrice, Brown Steve D, D'Souza Abigail, Fuchs Helmut, Gailus-Durner Valerie, Guimond Alain, Hérault Yann, Angelis Martin Hrabě DE, Lux Aline, Mittelhaeuser Christophe, Nutter Lauryl M J, Palkova Marcela, Lindovsky Jiri, Petit-Demouliere Benoit, Prochazka Jan, Bradaschia Vivian, Kelsey Lois, McKerlie Colin, Raishbrook Miles Joseph, Sedlacek Radislav, INTERNATIONAL MOUSE PHENOTYPING CONSORTIUM, Lanoue Louise, Lloyd K C Kent, Roux Michel J, Bermingham-McDonogh Olivia
Аннотация
METHODS: We evaluated phenotype data for concurrent retinopathy and hearing abnormalities in single-gene KO mice generated by the International Mouse Phenotyping Consortium (IMPC). A search was performed to determine whether each gene had been previously associated with retinopathy and/or deafness in humans. Bioinformatic tools were used to predict protein interactions, molecular functions, signaling pathways, and the expression of human orthologues of candidate genes in the retina and inner ear.
RESULTS: We identified 18 single-gene KO lines exhibiting hearing abnormality and retinopathy after ear and eye examinations, respectively, and/or by histopathology. The molecular functions and signaling pathways of the human orthologues of the 18 candidate genes partially overlapped with those of USH genes. Particularly, FER and DYRK1B proteins were predicted to interact with proteins encoded by known ciliopathy genes. ADIPOR1, ATP8B1, and MPDZ were associated with retinal degeneration in humans. CHSY1 and IDUA may be pathogenic causes of hearing impairment in people. Furthermore, CHSY1, CSTB, and SPRED1 were located adjacent to unsolved genetic loci related to USH.
CONCLUSIONS: A screen of 9139 KO mouse lines revealed 18 candidate genes exhibiting both retinal and inner ear abnormalities consistent with the principal clinical features associated with USH. As the observed phenotypes are attributed to gene deletion in mice, these genes warrant further study to determine the causation of retinal degeneration and hearing loss in patients.