EASTBIO Developing Ovine Immune ‘Omics for sheep genomic improvement

Royal (Dick) School of Veterinary Studies / The Roslin Institute

The aim of this project is to use an ‘omics approach to identify genetic variants that can potentially be used in development of a next generation of productive sheep breeds or crossbreeds resilient to the on-going effects of changing disease pressures.

A major constraint on sheep production worldwide is the level of biological inefficiency associated with highly prevalent infectious diseases. This project will focus on understanding how genetic variation is driving immunity to infectious disease and exploiting the derived information in a breeding programme to mitigate future disease risk.

We will prioritise variants, underlying immunity, for genomic selection in sheep using a TWAS approach. Transcriptome-wide association analysis (TWAS) is a very powerful approach for studying the genetic architecture of complex traits. A key component of this approach is to build a model to impute gene expression levels from genotypes by using samples with matched genotypes and gene expression data in a given tissue or cell type (Hu et al., 2019).

As such the project has four main objectives: i) Collection of blood samples from 60 sheep, Ficoll separation and MACS cell sorting of immune cell types (e.g. monocytes, B-Cells and T-Cells; ii) RNA-extraction from one cell type (the remainder of the cell types will be banked as a valuable resource) and mRNA-sequencing; iii) Identification of functional variants using a TWAS approach, based on analysis of the RNA-Seq data with genotype data from the same animals; iv) Ranking and prioritisation of the functional variants in genomic selection algorithms.

Extrapolating from human studies with 60 animals we expect over 1800 genes to have a heritability p value < 0.01 and a suitable prediction model for imputation. By co-localising expression information with loci identified in GWAS for immune-mediated traits in sheep (e.g. Zhang et al. 2018), we will identify functional immune variants that can be prioritised in genomic selection algorithms.

The strategic goal of this project is to help the sheep industry become ready for a global trend towards using genomic selection to design efficient breeds/breeding programmes. Our project will contribute to the competitiveness of the sheep sector in response to the on-going and rapid effects of disease pressures. This information will effectively help to ‘future-proof’ the sheep sector against potential challenges from pathogens and provide a ‘proof of concept’ for other potential pressures the industry may face going forwards.

The successful applicant will join a research group focusing on the analysis of gene expression in sheep (Clark et al. 2017). Training will be provided in bioinformatic analysis, immune cell isolation and RNA extraction. The project offers the opportunity to work within the International Sheep Genomics Consortium (ISGC). Roslin Technologies are the CASE partner. They will provide a 3-month research placement and, with SRUC, will facilitate integration of the variants in a breeding programme for genomic improvement in sheep. As such the project will provide significant travel, collaboration and training opportunities, providing an excellent start to any research career.

Eligibility:
All candidates should have or expect to have a minimum of an appropriate upper 2nd class degree. To qualify for full funding students must be UK or EU citizens who have been resident in the UK for 3 years prior to commencement.