An Epigenetic Aging Clock for Cattle Using Portable Sequencing Technology

Abstract

Extensively grazed cattle are often mustered only once a year. Therefore, birthdates are typically unknown or inaccurate. Birthdates would be useful for deriving important traits (growth rate; calving interval), breed registrations, and making management decisions. Epigenetic clocks use methylation of DNA to predict an individual’s age. An epigenetic clock for cattle could provide a solution to the challenges of industry birthdate recording. Here we derived the first epigenetic clock for tropically adapted cattle using portable sequencing devices from tail hair, a tissue which is widely used in industry for genotyping. Cattle (n = 66) with ages ranging from 0.35 to 15.7 years were sequenced using Oxford Nanopore Technologies MinION and methylation was called at CpG sites across the genome. Sites were then filtered and used to calculate a covariance relationship matrix based on methylation state. Best linear unbiased prediction was used with 10-fold cross validation to predict age. A second methylation relationship matrix was also calculated that contained sites associated with genes used in the dog and human epigenetic clocks. The correlation between predicted age and actual age was 0.71 for all sites and 0.60 for dog and human gene epigenetic clock sites. The mean absolute deviation was 1.4 years for animals aged less than 3 years of age, and 1.5 years for animals aged 3–10 years. This is the first reported epigenetic clock using industry relevant samples in cattle.

Genomic characterization of autozygosity and recent inbreeding trends in all major breeds of US dairy cattle

“…The genomic region harboring these genes has been previously associated with age at puberty and calving difficulty in beef cattle (Fernández et al, 2014;Purfield et al, 2020). Furthermore, Hayes et al (2021) found the ISL1 gene to be significantly associated with maturity in cattle. Previous studies have reported low and positive genetic correlations (r g = 0.22-0.28) between age at reproductive milestones (puberty, first calving) and calving difficulty (Bennett and Gregory, 2001;Berry and Evans, 2014).…”

Imputation strategies for near real-time genomic prediction using nanopore sequencing

“…ONT sequence data from 64 samples (Additional file 1) sequenced in Hayes, Nguyen [27] on a MinION was subsampled down to 2x, 1x, 0.5x, 0.1x and 0.05x sequencing coverage. The samples included Brahman and Droughtmaster breed animals.…”

DNA methylation profile in beef cattle is influenced by additive genetics and age

“…Marttila et al 11 observed that age-associated DNA hypermethylation seems to originate from programmed developmental changes while DNA hypomethylation could result from environmental in uences 11 . Furthermore, DNAm pro les in several species have been demonstrated to predict individuals' biological age, known as epigenetic clocks [12][13][14][15][16][17][18][19][20][21][22][23] . Recently, Caulton et al 13 reported a prediction accuracy of 0.95 for epigenetic clocks based on DNAm in a dairy herd.…”

“…More recently, based on DNAm of liver and blood samples of horses, Horvath et al16 reported accuracy greater than 0.95 for epigenetic clocks.Kordowitzki et al 18 developed epigenetic clocks of reproductive aging in oocytes and blood from cattle with accuracy greater than 0.86. Hayes et al17 achieved a prediction accuracy for birthdate of 0.71 in beef cattle from a diverse genetic background. These results are encouraging for using epigenetic clocks to estimate age in cattle reared in extensive production systems, which usually have unknown or inaccurate birthdates records.…”

“…However, accurately predicting differences in birthdates among cohorts requires substantial reductions in the average error reported by Hayes et al that could perhaps be achieved with much larger training sets. Overcoming the challenges of industry birthdate recording with epigenetic clocks could contribute to herd management and estimation of genomic breeding values for economically important traits that depend on accurate age records, such as growth rate and calving interval17 . Given epigenetic clocks have proven to be accurate predictors of biological age, epigenetic indicators could provide a mechanism to infer age-related pathologies and identify genetic, environmental, or lifestyle factors that accelerate or slow aging in humans and livestock30 .…”