Research Article: Longitudinal changes in telomere length and associated genetic parameters in dairy cattle analysed using random regression models

Date Published: February 13, 2018

Publisher: Public Library of Science

Author(s): Luise A. Seeker, Joanna J. Ilska, Androniki Psifidi, Rachael V. Wilbourn, Sarah L. Underwood, Jennifer Fairlie, Rebecca Holland, Hannah Froy, Ainsley Bagnall, Bruce Whitelaw, Mike Coffey, Daniel H. Nussey, Georgios Banos, François Criscuolo.

http://doi.org/10.1371/journal.pone.0192864

Abstract

Telomeres cap the ends of linear chromosomes and shorten with age in many organisms. In humans short telomeres have been linked to morbidity and mortality. With the accumulation of longitudinal datasets the focus shifts from investigating telomere length (TL) to exploring TL change within individuals over time. Some studies indicate that the speed of telomere attrition is predictive of future disease. The objectives of the present study were to 1) characterize the change in bovine relative leukocyte TL (RLTL) across the lifetime in Holstein Friesian dairy cattle, 2) estimate genetic parameters of RLTL over time and 3) investigate the association of differences in individual RLTL profiles with productive lifespan. RLTL measurements were analysed using Legendre polynomials in a random regression model to describe TL profiles and genetic variance over age. The analyses were based on 1,328 repeated RLTL measurements of 308 female Holstein Friesian dairy cattle. A quadratic Legendre polynomial was fitted to the fixed effect of age in months and to the random effect of the animal identity. Changes in RLTL, heritability and within-trait genetic correlation along the age trajectory were calculated and illustrated. At a population level, the relationship between RLTL and age was described by a positive quadratic function. Individuals varied significantly regarding the direction and amount of RLTL change over life. The heritability of RLTL ranged from 0.36 to 0.47 (SE = 0.05–0.08) and remained statistically unchanged over time. The genetic correlation of RLTL at birth with measurements later in life decreased with the time interval between samplings from near unity to 0.69, indicating that TL later in life might be regulated by different genes than TL early in life. Even though animals differed in their RLTL profiles significantly, those differences were not correlated with productive lifespan (p = 0.954).

Partial Text

Telomeres are located at the ends of linear chromosomes. They consist of non-coding nucleotide tandem repeats (TTAGGG in vertebrates) and attached proteins of the shelterin complex [1–3]. Since telomeres were first shown to shorten with the number of cell divisions in vitro [4], they have been intensely studied in relation to ageing and lifespan in various species in vivo [5–9]. Such studies have reported mixed results. While some observed a positive correlation between telomere length and longevity [5,10–12], others found no relationship [13,14]. Many authors claimed that longitudinal studies were necessary to better understand telomere dynamics within the individual, and to investigate the association of not only telomere length but also change in telomere length with lifespan [10,15–17]. In longitudinal studies of Alpine swifts and Seychelles warblers, faster telomere attrition, but not telomere length per se, was associated with poorer survival [18,19]. In humans telomere length maintenance was associated with better survival than telomere length attrition in patients with cardiovascular disease [20,21]. However, the relationship between telomere length attrition and survival has not been investigated in a livestock species to date.

Raw RLTL measures ranged from 0.693 to 1.727 with a mean of 1.082. The coefficient of variation was 0.162. The model that included the animal identity as a random effect fitted the data significantly better than a model including only the fixed effects (delta AIC = 204.97) suggesting that animals differed significantly in their average RLTL across time. Fitting animal identity with pedigree information further improved the model fit (delta AIC = 55.46). Fitting an individual curve for each animal (using a quadratic Legendre polynomial) additionally increased the model fit (delta AIC = 3.24), meaning that monthly RLTL dynamics also differ among individual animals. A quadratic Legendre polynomial fitted marginally better than a linear function (delta AIC = 2.07) and had the advantage that the same order of Legendre polynomial was fitted to the fixed and the random effect which facilitates interpretation of the results.

This is the first study exploring individual RLTL profiles of farm animals across time and the largest longitudinal telomere study outside the human literature so far. Our results suggest that individual cattle differ in their RLTL dynamics over life. Although most of the difference between animals is explained by a different average RLTL (intercept) (94.7%), a small proportion is due to different shapes of RLTL profiles (5.3%). This is an important observation that justifies the further investigation of differences in telomere profiles in association with traits of interest such as health, fertility and mortality. The only other study we are aware of that used random regression models for the analysis of longitudinal telomere data did not report a significant difference in telomere dynamics among Seychelles warblers [18], which might have been due to the relatively small sample size of that study.

 

Source:

http://doi.org/10.1371/journal.pone.0192864

 

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