Accepted_test

Single nucleotide polymorphisms associated with the development of accelerated aging phenotype in OXYS rats
by Devyatkin Vasiliy | Redina Olga | Kolosova Nataliya | Myraleva Natalia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia | Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia
Abstract ID: 394
Event: BGRS-abstracts
Sections: Section “Genetics and systems biology of aging”

The genetic basis of predisposition to the development of comorbid age-related conditions remains unclear. The goal of this work was to search for nucleotide variants that are associated with the early development of a phenotype similar to human geriatric diseases in OXYS rats (ICiG SB RAS), a unique model of accelerated aging. With mildly elevated blood pressure, OXYS rats develop cataracts, cardiomyopathy, retinopathy similar to AMD in humans, and key features of AD in the absence of mutations in the App, Psen1, and Psen2 genes.

Comparison of transcriptome data from the prefrontal cortex, hippocampus, and retina of OXYS rats with the reference genome of BN/NHsdMcwi rats revealed 42478 SNPs, among which 2105 SNPs are not found in the genomes of the rat strains used as controls. 7 SNPs leading to functionally significant structural rearrangements of transcripts and 33 SNPs causing nonsynonymous amino acid substitutions characterized by a strong effect on protein structure and/or function in OXYS rats were identified as SNPs that presumably contribute to accelerated aging in OXYS rats. These SNPs are located in genes associated with aging and neurodegenerative diseases and involved in the main metabolic and signaling pathways associated with the development of hypertension, AD, AMD and other age-related diseases. At the same time, we did not identify mutations that could unambiguously determine the phenotype of OXYS rats, which indicates either the cumulative effect of multiple gene disorders or factors not associated with mutations in the coding regions of the genome of OXYS rats.