Measurements of telomere length at different life stages as predictive biomarkers of health, reproduction and longevity in dairy cattle

Lead Research Organisation: University of Edinburgh
Department Name: The Roslin Institute

Abstract

The key concept of the proposed work is based on three tenets:

1. Health, reproduction and longevity are key factors influencing the sustainability and profitability of the livestock industry in the UK and internationally. In addition to bearing considerable economic significance, these factors affect animal welfare, the environmental footprint of livestock operations, and the acceptability of animal products by consumers. Therefore, improvement of these traits will yield multi-faceted benefits.

2. Given the complexities and time requirements affecting the accurate recording of these traits, there is a need for reliable, early-life predictors that could provide early warnings for poor health, reproduction and longevity, effectively contributing practical tools for improvement.

3. Recent advances in human and laboratory animal research have revealed potentially useful biological markers that are associated with lifespan, as well as age and age-related conditions.

The proposed project aims to identify an early-life biomarker to predict health, reproduction and longevity in dairy cattle.

For this reason, the project will use a comprehensive database of cows raised in the experimental herd of the Crichton Royal Farm in Scotland. Animals belong to two different genetic lines (selected for high vs. average production) and two diet groups (high vs. low protein intake) and are closely monitored from the time of birth until they die or are removed from the herd. The database comprises records of individual animal pedigree, performance, feed intake, disease and reproductive events, and longevity. Detailed environmental descriptors associated with these records are also included in the database.

Approximately 1,000 animals from this herd have already been blood sampled at birth and then in 6-month intervals. These samples will be used to measure the length of the telomeres of each cow across her lifetime. Telomeres are small structures capping the chromosomes' ends in the animal cells and are known to be associated with aging in humans. Changes in telomere length measures obtained in the proposed study will be monitored throughout the animals' life and analysed together with data pertaining to health events, reproductive issues and length of productive life. These analyses will establish the link between animal telomere length and health, reproduction and longevity.

To achieve its objectives, the project will draw on complementary expertise in animal science, genetics, biotechnology, physiology and biology.

The potential applications and benefits of this study are as follows:

1. This is the first ever study in food producing animals that looks at the way telomeres change across time and how this change may relate to important animal traits. Also for the first time the effect of many genetic and environmental factors on telomeres and longevity will be examined.

2. The outcome of the project will bring a better understanding of the process of ageing of milk producing cows and will identify an early-life indicator that predicts the animals' future health, reproduction and longevity.

3. The end result will be an easily applicable, animal-friendly biomarker that could be used as a management and selection tool to improve the robustness, welfare and survival of dairy cattle, and reduce the rate of involuntary removal of high yielding animals from the herds. Further ramifications of the envisaged improvement include a healthier background for the production and consumption of animal products, and a lower environmental footprint of the sector as a whole.

4. Knowledge acquired in this project may have longer reaching consequences for animal conservation programmes to improve survival of rare animal breeds and endangered species, as well as detailed studies to better understand the aging process in other species including humans.

Technical Summary

We propose the first ever longitudinal study of telomere length (TL) in relation with health, reproduction and longevity (HRL) of dairy cattle. Key objectives include:

1. Examination of the genetic and environmental factors affecting TL.
2. Evaluation of the link of TL with animal production and HRL.
3. Identification of an early-life TL measure as a predictive biomarker of HRL.
4. Demonstration of the utility of the biomarker in breeding programmes.

A resource population of 1,000 dairy cows raised at the SRUC research herd will be used. Animals are split into two equally sized genetic lines (high vs. average genetic merit for production) and two diet groups (high vs. low protein intake) as part of an on-going selection and feeding experiment. Animals are closely-monitored on a daily basis from birth to death or removal from the herd. A dense phenotypic database including individual animal performance, feed intake, metabolic load, health status and reproductive events is already in place.

Blood samples have been taken from these animals at 6-month intervals starting at birth. These samples will be used to extract DNA from blood cells and measure TL with a quantitative Polymerase Chain Reaction. Repeated measures of TL for each animal will determine the telomere attrition rate. The bovine TERT gene locus will be sequenced and influential polymorphisms will be determined with association analyses.

Mixed statistical models will be developed for data analyses to:

1. Portray the TL profile across an animal's lifetime.
2. Quantify the effect of genetic and environmental factors on TL.
3. Estimate heritability of TL.
4. Estimate genetic and phenotypic correlations of TL with production and HRL.
5. Assess the predictive capacity of TL as a biomarker of HRL.

Cross-validation will be used to identify the most accurate telomere predictor. A simulation study will be designed to demonstrate the optimal way of incorporating this into breeding programmes.

Planned Impact

The sustainability and profitability of dairy farms depend on cows producing milk normally for at least 3-4 years. Given that dairy cows start producing milk when they calve for the first time (approximately 2 years old) the desirable length of life in the herd is at least 5-6 years. Cows that leave the herd earlier due to diseases or poor fertility incur considerable costs for the farmer. Currently, nearly 20% of dairy cows in the UK fail to reach their first calving and onset of milking whilst many more leave the herd before achieving their full production potential.

This project offers an innovative approach, utilises unique data and combines complementary scientific expertise in order to develop knowledge and practical, early-life tools to predict health, reproduction and longevity of dairy cows. The project will also investigate and propose optimal ways of incorporating these tools in the national breeding and genetic improvement programme. Thus, the outcomes of this project will contribute directly to the reduction of health and reproductive problems, the enhancement of dairy cow longevity and, consequently, the improvement of animal welfare. Benefits would apply to individual cow, farm and population levels.

In this respect, the impact of the proposed work is expected to be multi-faceted:

1. Early identification of animals prone to repeat health and reproductive problems will assist selection and replacement strategies, and minimise animal suffering.

2. Dairy farmers will directly benefit from improved cow longevity as cost of replacements (i.e. young animals kept in the herd to replace older animals at the end of their productive utility) will decrease. More offspring will then be obtained from animals with high genetic merit. The intensity of selection will increase as there will be more selection candidates to choose from. Fewer health and reproductive problems will also signify enhanced animal welfare.

3. The dairy industry will benefit from advances and optimisations of the genetic improvement programmes brought about by outcomes of the proposed project. Currently, the economic benefits of such programmes in the UK are worth nearly £106 million/year; more than half of this is being realised by improvements in cow health, reproduction and longevity.

4. Improved health and longevity of the milking cows will enhance the health profile of their products and, eventually, the image of the sector and acceptability by consumers.

5. Benefits in the dairy industry will permeate the entire food producing animal sector, where outcomes from this project could be used as models for pertinent activities.

6. Environmental benefits are expected to accrue because of the reduced number of on-farm replacements, the latter accounting for 27% of the methane produced on-farm.

7. Policy makers and government can use outcomes and evidence from this project in the formulation and regulation of actions aiming at animal welfare and the social acceptability and environmental image of the livestock sector.

8. Considerable scientific benefits are anticipated which are described in detail in the Academic Beneficiaries section. Staff hired for the project will have the opportunity for training, attend courses and conferences, and develop scientific and professional skills in the laboratory, computer, numerical and quantitative analyses.

9. The UK as a whole will benefit through the links between the scientific partners in the project and their industry contacts, ensuring quick uptake and implementation of the research results, contributing to the enhancement of farm output, health and living standards.

This is a 3-year project whose benefits are expected to start materialising as soon as the first results become available and continue long after the completion of the project.
 
Description Assessed and devised best PCVR-assay protocol.

Used the above to demonstrate for the first time that bovine RLTL is a heritable trait, and its association with productive lifespan may be used in breeding programmes aiming to enhance cow longevity.
Exploitation Route Working towards biomarker assay.
Sectors Agriculture, Food and Drink

 
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