|dc.contributor.author||Seeker, Luise Avelina||en
|dc.description.abstract||Telomeres form protective caps at the ends of linear chromosomes. They consist of
repetitive DNA nucleotides and associated proteins of the shelterin complex. In vitro
telomeres become shorter during cell division and when a critical shortness is
reached they trigger a DNA damage response that leads to replicative senescence
or apoptosis. Telomere shortening is a recognised hallmark of cellular ageing and
seems to be also associated with organismal ageing. Telomere length (TL) and the
rate of shortening vary across individuals and several studies have found that short
telomeres and fast telomere depletion are associated with poor survival and early
onset of age related diseases. However, longitudinal studies are needed to better
understand the relationship of TL and TL dynamics with longevity measures.
Relevant studies on livestock species are largely missing from the literature.
In the dairy industry, farmers are forced to cull a considerable percentage of their
heifers and cows at a young age due to fertility problems or diseases. As a
consequence many replacement heifers have to be reared to maintain a specific
herd size. This results in increased costs, consumption of resources, and damage to
the environment. Breeding for an improved productive lifespan is difficult because
longevity measures are recorded at the end of life and are known to have a low
heritability. Therefore, the expected genetic improvement is generally slow, but
could be considerably accelerated if an early life heritable biomarker was identified
that is predictive of productive lifespan and could be used for animal selection. The
question is if TL could be used as such a biomarker.
The objectives of this thesis were to 1) develop robust methods to measure average
relative leukocyte TL (RLTL) in cattle, 2) examine RLTL dynamics with age at a
population as well as at an individual level, 3) estimate genetic parameters and 4)
assess the association of RLTL and RLTL dynamics with productive lifespan.
A quantitative polymerase chain reaction (qPCR) based assay developed for human
studies was adapted to cattle and delivered robust results (repeatability > 80%,
coefficient of variation=0.05). Different DNA extraction methods were tested for their
effect on RLTL measurements and it was demonstrated that fast silica based DNA
extraction methods are suitable for telomere projects which can improve the sample
throughput and enable large-scale projects. Subsequently, RLTL in 1328 whole
blood samples of 308 Holstein Friesian dairy cows and additionally in 284 whole
blood samples of 38 female calves was measured. Repeatability and random
regression models were used for the statistical analysis of telomere data.
RLTL decreased considerably within the first year of life, but remained relatively
stable afterwards at population level. Animals varied significantly in their amount and
direction of telomere change. The genetic correlation between consecutive
measurements in the same individual weakened with increasing sample interval
from r=1 to r=0.69 which indicates that TL in the beginning of life might be under a
different genetic control than TL later in life. For the first time in a livestock species
we calculated heritability estimates for RLTL which were high (0.32-0.38) and
remained constant over life. Long telomeres at birth were not predictive of better
productive lifespan. However, animals with long RLTL at the ages of one and five
years had a survival advantage. Also, animals that showed less average RLTL
attrition over their lives remained in production for longer.
TL dynamics differed among individuals and a considerable subset of individuals
demonstrated telomere lengthening between consecutive measurements. On
average, telomeres tend to shorten early in life and then remain relatively constant.
While TL is a heritable trait throughout lifetime, telomere change is not heritable.
Short TL at specific ages and telomere attrition over life were associated with poorer
|dc.publisher||The University of Edinburgh||en
|dc.relation.hasversion||Seeker, L.A. et al., 2018. Longitudinal changes in telomere length and associated genetic parameters in dairy cattle analysed using random regression models. Plos One, pp.1–15. Available at: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0192864.||en
|dc.relation.hasversion||Seeker, L.A. et al., 2016. Method specific calibration corrects for DNA extraction method effects on relative telomere length measurements by quantitative PCR. PLoS ONE, 11(10), pp.1–15. Available at: http://dx.doi.org/10.1371/journal.pone.0164046.||en
|dc.subject||random regression models||en
|dc.subject||telomere length dynamics||en
|dc.title||Characterisation of telomere length dynamics in dairy cattle and association with productive lifespan||en
|dc.type||Thesis or Dissertation||en
|dc.type.qualificationname||PhD Doctor of Philosophy||en