Texel genomics of disease resistance pdf

TEXEL

A Texel Sheep Society Publication

Genomics of disease resistance

National Agricultural Centre, Stoneleigh Park, Kenilworth, Warwickshire, CV8 2LG Tel: 02476 696 629 Fax: 02476 696 472 Email: office@texel.co.uk

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INTRODUCTION

T

he ‘Genomics of mastitis in meat sheep’ project is an exciting Society-led research project supported by world leading geneticists at SRUC. This £450,000 pioneering project funded by InnovateUK and the Society uses cutting edge genomic technology to gain a better insight into the genetic ability of Texel sheep to resist mastitis infections.

The aim is to provide a new breeding tool and production of genomic breeding values for Texel breeders to help breed sheep with an innate genetic resistance to mastitis. Additionally, with Texel sired ewes now making up more than 12% of the UK ewe flock (AHDB Breed census 2012), the impact of this work will quickly influence the industry.

As an evolutionary step for the UK sheep industry, this research will use novel tools in genomic studies to support genetic improvement from hard to measure traits. Mastitis is a substantially important and fatal disease that causes major production losses across the entire industry The Society is renowned for being a progressive, well-structured and financially robust organisation. This combination of strengths provides an ideal platform for developing genomic studies by utilising the large Texel population and dataset, supported by enthusiastic and proactive Texel breeders. In this way, new challenges and opportunities in breeding Texel sheep can be explored.

A cluster of genetically well connected pedigree performance recorded flocks, along with a large amount of specific data (phenotypes) from more than 2500 ewes is being used for the project. Background data on performance and pedigree history that is already being collected from the breed as part of their general production system is an important component of the project. Combined with a world class team of sheep geneticists and researchers, the project has one of the best frameworks available to make considerable progress into this area of genomic research.

PROJECT AIMS • Predict both genetic (EBVs) and genomic estimated breeding values (GEBVs) for mastitis resistance • Identify the most appropriate measurements (phenotypes) for Breeders to record on-farm • Improve breed resistance to mastitis and reduce antibiotic use • Provide farmers with new tools to • Improve animal welfare • Improve production • Increase overall sustainability

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Footrot research - An added extra!

Research into the genomics of footrot resistance within the breed is also being carried out.

Each ewe, if eligible, is also foot scored helping to develop data held on the breed. DNA samples are taken from each ewe and full pedigree and performance data is also available.

The objectives of this project bolt-on, are similar to the mastitis project and to support development of previous research outcomes between the SRUC and Society in 2008.

The primary aim is to produce Genomic Breeding values (GEBV’s) for footrot resistance for Texel sheep providing the potential to add a significant benefit initially for Texel breeders, and the wider industry as those Texel genetics are used in pure bred and cross breeding programmes.

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Technical team collect measurements and samples.

WHY FOOTROT? Similarly to mastitis, SRUC previous research showed that there is a genetic component for resistance to footrot.

• Footrot is the main form of lameness in sheep and a major welfare concern within the sheep industry • Footrot is a major cause of production losses with: • Reduced growth rates • Reduced fertility • Reduced milk yield • It is estimated that footrot costs about £5/ lamb and £7/ewe

Cluster of phenotype farms

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WHAT’S INVOLVED? The flocks located throughout the UK involved in this study form a cluster of unique “Phenotype Farms” solely for the purpose to generate measurements for ‘hard to measure’ traits.

• A Society technical team visit each farm to collect measurements and each ewe is sampled using a welfare friendly novel nasal sampling device for the collection of DNA. • The DNA is sent to a genomics laboratory and extracted and analysed using the latest genomics tests. Currently two SNP Chips are used, the 50K and 700K. • The resultant genotypes are stored as part of the Texel whole breed “gene-tex” genomic reference population. This is a valuable and essential resource containing a rising number of over 3000 high density genotypes that will support this research and also new genomics research projects in the future.

California Milk Test.

Right = Subclinical/Clinical Mastitis identified

• Commercial application will be in the form of novel GEBVs and future identification of genomic markers of great importance for the breed.

The measurements being researched are taken in the form of • Scores for udder conformation and teat placement/alignment.

• Milk samples are taken and tested at a laboratory for Somatic Cell Counts (SCC) as well as tested on farm using the California Milk Test (CMT) Researchers aim to understand the relationships between udder, teat dimensions and positioning to the occurrence of mastitis. Additionally, foot scores are taken to assess the structure of the foot and to quantify if any infection is present. The data collected is then analysed by SRUC to assess whether Texel ewes are able to resist both mastitis and/or footrot and identify the variety of genes involved.

The research team at SRUC plan to develop Texel breed specific genomic breeding values (Texel SNP Key), for mastitis and potentially foot rot resistance.

These genomic breeding values (GEBV’s) will offer similar uses to that of normal EBVs, building in greater accuracy and precision thereby supporting faster rates of genetic gain for the selected trait.

The data collection phase will span two breeding seasons (2015 and 2016), with farms visited twice in each breeding season collecting measurements from mostly the same ewes at each visit. These visits take place four weeks post lambing and at weaning.

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Milk sample for laboratory Somatic Cell Count (SCC)

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Is mastitis worth all this effort?

Previous research suggests 5% of ewes (all breeds/and crosses) in the UK suffer from acute mastitis and a further 20-30% suffer from sub-acute mastitis. This coupled with losses (through culling and deaths) of 7-12% of breeding ewes a year due to intramammary infections, makes mastitis a significant issue for the entire sheep sector.

Although the full affect of mastitis in sheep is not fully understood, mastitis impacts on the health, welfare and productivity of sheep in the following ways: • Loss of milk production

Progress made so far • Recruitment protocol and cluster of dedicated breeders has been established • Year one data collection and genotyping has been completed • SRUC researchers are undertaking preliminary analysis • Creation of a Texel genomic reference population has been developed and will continue to be expanded to ensure greater accuracy of genomic predictions into the future • An additional 1000 pedigree performance recorded rams have been genotyped using the High Density 700K SNP Chip

• Premature culling of ewes • Altered milk composition • Decreased lamb growth rates • Possible death of ewes To exacerbate the issue, there is no sign of a vaccine for mastitis being produced anytime soon due to the many types of bacteria that can cause the disease. By applying genomic studies, that are proven to support the genetic improvement of ‘hard to measure’ traits, the Society led project is applying the right tool at a breed level to begin to manage the challenge of mastitis at an industry wide level. By recording mastitis, breeders can use genetic and genomic information to ensure that high-performance does not come hand in hand with an increase in disease levels.

“Society led project is applying the right tool at the a breed level to begin to manage the challenge of mastitis at an industry level”

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WHY USE GENOMICS TO MANAGE MASTITIS AND FOOTROT? Genomics is the study of genes. In animal breeding, genomics are used to understand which genes influence certain traits. By using SNPs to detect tiny variations in DNA sequences a road map can be developed that displays gene/trait influence. It is these tiny variations in the animals DNA which can explain which particular sequence of DNA is responsible for a trait of interest, for example a disease or meat quality trait. For some diseases a single gene can be identified that has a great effect on a single trait, such as Scrapie, where a simple DNA test can provide information that shows an animal’s susceptibility or resistance.

With Mastitis and footrot a ‘single gene’ effect isn’t expected, although there may be genes of major influence on mastitis resistance or susceptibility. It is most likely that several hundred different gene variants (or ‘SNPs’) are implicated in mastitis resistance which the technology being used should be able to identify. As such, different methods are required and this project focuses on producing “genomic breeding values” as the tool to breed sheep of greater disease resistance.

This approach requires the development of accurate methods of scoring for a disease/trait by trained operators and collecting the DNA from a reference population. Using the latest High Density genotypes from the same reference population, and by developing a breeding value based on a set of mathematical algorithms, to interpret the data and DNA, a single genomic breeding value (GEBV) will provide breeders with a bench mark to select sheep for greater resistance to disease.

Genomic studies is now an important technology within the livestock industry, used widely in the dairy, pig and poultry sectors with considerable breeding advances being achieved, reducing cost by removing the reliance on progeny testing whilst fast tracking genetic improvement with improved accuracies of breeding values. There is no doubt the technology will allow similar advances to be made in certain sections of the sheep industry.

Ultimately, genomics will give breeders far greater accuracy and precision when assessing the genetic merit of a sheep than standard EBVs, particularly for hard to measure traits.

This will not mean conventional EBVs become redundant, or remove the need for trait measurements. Rather, genomic technology is dependent on having a large number of data collected, especially for hard to measure traits, traits that are measured later in life or are only expressed in one sex. GEBV’s will be essential when assessing the genetic merit for meat quality, maternal ability and health traits.

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DNA collection using novel nasal sampling device.

SUITABILITY OF THIS TECHNOLOGY FOR THE TEXEL BREED. Getting started in genomics provides major challenges.

• Ideally a large population with similar genetic makeup is required i.e. one breed. This is because the genes responsible for certain traits can be different between breeds.

• Sheep need to be well recorded with lots of pedigree and performance data behind them. These are called phenotypes.

• Large amounts of genotyped animals are needed This forms the “Reference Population” used for the estimation of GEBVs. • The lead organisation needs the right infrastructure, financial resources and cooperation between many breeders, (or else just a very large flock)!

These simple facts limit the ability of most of the sheep industry to exploit genomics as many breed populations are small.

Managing at a multi breed level also creates many challenges.

The Texel Society has been progressive in technology development and transfer for decades, driving performance recording for many years. The Texel breed is well suited to genomic studies due to the large number of recorded Texels and the high volume of trait data stored by its members. The Societies appetite to drive change and develop the use of this technology in the breed provides the next chapter in the development of the breed into the future.

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HOW CAN GENOMICS HELP THE TEXEL BREED? Genomics will be of most use when making breeding selection for hard to measure traits, examples include hardiness, maternal ability, meat quality and disease resistance.

Genomics can potentially assess these traits much more easily and determine the raw genetic potential of an animal to perform better for the given trait.

GEBV’s for meat quality traits could determine how good the meat eating experience would be and allow for improved selection in breeding programmes. Potentially, DNA sampling and genotyping a young unproven lamb, a well managed genomic breeding programme could produce GEBV’s for the given traits, increasing genetic improvement and shortening the generation interval.

The opportunities provided by including genomics in the Texel breeding programmes is vast, speeding up genetic gain in the traits that are already selected for, and by making additional advances in novel traits such as disease resistance.

MOVING FORWARD The benefits of this work will not end here as the implications of this initial study will be a game changer. Helping to identify superior genetic lines that provide solutions for commercial producers. A catalyst to influence the increased use of modern breeding tools, to benefit the Texel breeds genetic improvement across a wide range of traits, both now and in the future.

By the end of 2016 there will be more than 2500 50k high density genotypes stored as well as up to 1000 700k high density genotypes in the Texel reference population. Selection methods for assessment of hard to measure disease traits will have been developed to aid disease prevention. Supporting the increase in productivity, reducing wastage through improvements in ewe longevity, directly benefiting greenhouse emission targets, whilst improving health and welfare, by reducing reliance on antibiotics.

This alone is a massive step forward for the Society, supporting the Society’s genomic programme. The challenge remains for the industry and the breed to identify traits of commercial importance. Develop accurate measurement strategies and wide scale data collection to support the development of novel Genomic Breeding Values.

With 27% of the rams used in the UK being Texels, there is a considerable scope to boost the performance of the UK sheep industry and the Texel breed.

Animal identification linked to Texel dataset key to research

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In touch with Texel

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@BritishTexel

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#addtexeladdvalue

Glossary Genomics: The study of genes EBVs: The prediction of an animal’s genetic merit based on a number of sources of information such as the animal’s own performance data and that of its relatives.

GEBVs: Genomic estimated breeding values. The prediction of an animal’s genetic merit using information gained from both the animal’s genotype and its phenotypic data.

SNPs: (Pronounced snip) Single nucleotide polymorphism is a form of variation within a DNA sequence. These variations are found in the DNA between and sometimes within genes and can act as markers to help geneticists to locate genes of interest.

SNP chip: A small piece of hardware that operates as the platform whereby DNA is placed on it in order to conduct the genotyping.

50K SNP chip: This contains around 50,000 SNPs uniformly distributed across the genome.

700K SNP chip: This contains around 700,000 SNPs distributed across the genome and has a far greater density than the 50k SNP chip.

SNP key: Algorithm linking genotypic information to prediction of genomic merit for a trait of interest.

Disease resistance: The ability of an animal to resist the manifestation of a disease. The animal may do this through having or developing an immune response to the infection.

Hard to measure traits: Traits that breeders struggle to collect reliable data on based on the nature of the trait.

Disease resistance, longevity and meat quality are just some of the traits that we consider to be ‘hard’ to measure traits that are often expensive to collect, too.

Genotyping: Undertaken in the lab whereby extracted DNA is processed to reveal individual genomic information.

California milk test: A reference test used to quantify the level of mastitis in milk. Traditionally used in dairy cows but also applicable to sheep. The test can determine the extent of infection on a graded 5-point scale to categorize the varying levels of mastitis present in the milk.

Somatic cell count: An indicator of the amount mastitis present in the milk, usually performed in a laboratory from a milk sample. White blood cells make up the majority of somatic cells and these increase in response to pathogenic bacteria in the udder.

Reference population: A cohort of animals used to collect phenotypic and genotypic information to generate genomic breeding values, GEBVs. The reference population is critical for the execution of robust estimates of GEBVs.

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www.texel.co.uk | 02476 696629 British Texel Sheep Society, National Agricultural Centre, Stoneleigh Park, Kenilworth, Warwickshire, CV8 2LG

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Tel: 024 7669 6629 Fax: 024 7669 6472 Email: office@texel.co.uk

www.texel.co.uk • tel: 024 7669 6629 • email: office@texel.co.uk