A missense variant in IFT122 associated with a canine model of retinitis pigmentosa

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Kaukonen , M , Pettinen , I-T , Wickstrom , K , Arumilli , M , Donner , J , Juhola , I-J , Holopainen , S , Turunen , J A , Yoshihara , M , Kere , J & Lohi , H 2021 , ' A missense variant in IFT122 associated with a canine model of retinitis pigmentosa ' , Human Genetics , vol. 140 , pp. 1569–1579 . https://doi.org/10.1007/s00439-021-02266-3

Title: A missense variant in IFT122 associated with a canine model of retinitis pigmentosa
Author: Kaukonen, Maria; Pettinen, Inka-Tuulevi; Wickstrom, Kaisa; Arumilli, Meharji; Donner, Jonas; Juhola, Ida-Julia; Holopainen, Saila; Turunen, Joni A.; Yoshihara, Masahito; Kere, Juha; Lohi, Hannes
Contributor: University of Helsinki, Medicum
University of Helsinki, Department of Medical and Clinical Genetics
University of Helsinki, Hannes Tapani Lohi / Principal Investigator
University of Helsinki, Department of Ophthalmology and Otorhinolaryngology
University of Helsinki, Juha Kere / Principal Investigator
University of Helsinki, Helsinki One Health (HOH)
Date: 2021-11
Language: eng
Number of pages: 11
Belongs to series: Human Genetics
ISSN: 0340-6717
URI: http://hdl.handle.net/10138/335462
Abstract: Retinitis pigmentosa (RP) is a blinding eye disease affecting nearly two million people worldwide. Dogs are affected with a similar illness termed progressive retinal atrophy (PRA). Lapponian herders (LHs) are affected with several types of inherited retinal dystrophies, and variants in PRCD and BEST1 genes have been associated with generalized PRA and canine multifocal retinopathy 3 (cmr3), respectively. However, all retinal dystrophy cases in LHs are not explained by these variants, indicating additional genetic causes of disease in the breed. We collected DNA samples from 10 PRA affected LHs, with known PRCD and BEST1 variants excluded, and 34 unaffected LHs. A genome-wide association study identified a locus on CFA20 (p(raw) = 2.4 x 10(-7), p(Bonf) = 0.035), and subsequent whole-genome sequencing of an affected LH revealed a missense variant, c.3176G>A, in the intraflagellar transport 122 (IFT122) gene. The variant was also found in Finnish Lapphunds, in which its clinical relevancy needs to be studied further. The variant interrupts a highly conserved residue, p.(R1059H), in IFT122 and likely impairs its function. Variants in IFT122 have not been associated with retinal degeneration in mammals, but the loss of ift122 in zebrafish larvae impaired opsin transport and resulted in progressive photoreceptor degeneration. Our study establishes a new spontaneous dog model to study the role of IFT122 in RP biology, while the affected breed will benefit from a genetic test for a recessive condition.
Subject: 1184 Genetics, developmental biology, physiology

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