Genome-wide association study and whole-genome sequencing identify a deletion in LRIT3 associated with canine congenital stationary night blindness.

Das, Rueben G; Becker, Doreen; Jagannathan, Vidya; Goldstein, Orly; Santana, Evelyn; Carlin, Kendall; Sudharsan, Raghavi; Leeb, Tosso; Nishizawa, Yuji; Kondo, Mineo; Aguirre, Gustavo D; Miyadera, Keiko (2019). Genome-wide association study and whole-genome sequencing identify a deletion in LRIT3 associated with canine congenital stationary night blindness. Scientific reports, 9(1), p. 14166. Springer Nature 10.1038/s41598-019-50573-7

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Congenital stationary night blindness (CSNB), in the complete form, is caused by dysfunctions in ON-bipolar cells (ON-BCs) which are secondary neurons of the retina. We describe the first disease causative variant associated with CSNB in the dog. A genome-wide association study using 12 cases and 11 controls from a research colony determined a 4.6 Mb locus on canine chromosome 32. Subsequent whole-genome sequencing identified a 1 bp deletion in LRIT3 segregating with CSNB. The canine mutant LRIT3 gives rise to a truncated protein with unaltered subcellular expression in vitro. Genetic variants in LRIT3 have been associated with CSNB in patients although there is limited evidence regarding its apparently critical function in the mGluR6 pathway in ON-BCs. We determine that in the canine CSNB retina, the mutant LRIT3 is correctly localized to the region correlating with the ON-BC dendritic tips, albeit with reduced immunolabelling. The LRIT3-CSNB canine model has direct translational potential enabling studies to help understand the CSNB pathogenesis as well as to develop new therapies targeting the secondary neurons of the retina.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Research and Veterinary Public Health (DCR-VPH) > Institute of Genetics

UniBE Contributor:

Jagannathan, Vidya and Leeb, Tosso

Subjects:

500 Science > 590 Animals (Zoology)
600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Springer Nature

Language:

English

Submitter:

Tosso Leeb

Date Deposited:

08 Oct 2019 10:42

Last Modified:

22 Oct 2019 17:37

Publisher DOI:

10.1038/s41598-019-50573-7

PubMed ID:

31578364

BORIS DOI:

10.7892/boris.133747

URI:

https://boris.unibe.ch/id/eprint/133747

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