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The rate of ageing-associated DNA methylation dynamics is a molecular readout of lifespan variation amongst mammalian species [Bis-PCR: dog]

ABSTRACT: We used buccal samples from two different dog breeds with well established differences in average lifespan to perform genome-scale identification of ageing-associated differentially methylated positions (aDMPs) in a total of 48 different dogs. A significant proportion of aDMPs that gained methylation with age replicated in an independent cohort. Furthermore, we also show that human aDMPs show similar ageing-associated dynamics at the homologous genomic regions in the dog. The replicated aDMPs show a faster rate of change with age in the shorter lived dog species. Strikingly, these aDMPs also show a faster rate of change with age in dogs overall compared with humans.

ORGANISM(S): Canis lupus familiaris

PROVIDER: GSE86058 | GEO | 2018/01/17

SECONDARY ACCESSION(S): PRJNA340147

REPOSITORIES: GEO

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Project description:Dogs are commonly used models of human inherited retinal disorders. Because the dog retina contains a macula-like region, dogs are susceptible to maculopathies with many shared genetic etiologies with humans. Human macular gene expression has been characterized and provides insight into the underlying basis of macular disease. We sought to compare macular gene expression profiles in dogs and humans and interrogate macular disease-associated genes for differential expression between macula and periphery. RNA sequencing was performed on 8mm samples of the dog macular region and superior peripheral region, sampling retina and retinal pigmented epithelium/choroid separately. Read sequences were mapped to CanFam3.1 and raw read counts were analyzed to determine significantly differentially expressed genes between macula and periphery within each tissue. A similar analytic pipeline was used with a published dataset of human samples to allow direct dog/human comparisons. Pathways and processes involved in significantly DEGs were identified using the Database for Annotation, Visualization and Integrated Discovery. Dogs and humans shared the extent and direction of macular retinal differential gene expression, with multiple shared biological pathways implicated in differential expression. There were fewer similarities between dog and human in the supporting tissues of the retina (the RPE, choroid, sclera). Many genes implicated in heritable retinal and macular disorders in both dogs and humans were differentially expressed between macula and periphery. Approximately 2/3 of genes associated with human age-related macular degeneration were differentially expressed in at least one human tissue, whereas approximately half were differentially expressed in at least one dog tissue. This work underpins the dog macular retinal region as analogous to the human macula in terms of differential gene expression. Whilst age-related maculopathy has not been described in dogs, evidence supports the study of aging of the macula and susceptibility to age-associated pathology in dogs.

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The rate of ageing-associated DNA methylation dynamics is a molecular readout of lifespan variation amongst mammalian species [Bis-PCR: dog]

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