Individual differences in immune responses are widely observed in nature and are likely to be a major factor underlying variation in disease resistance, health and evolutionary fitness. Understanding the role of genetics in immune variation is important in studies of immunology, medicine and evolutionary biology. If there is genetic variation in immune response, then it can respond to natural or artificial selection. However, efforts to identify the genetic basis of immune traits have been limited to humans, domesticated animals and laboratory rodents, which have regular treatment against prevalent infectious agents and/or live controlled environmental conditions. Widening immunological studies to include natural, untreated systems will help us understand the role of genetics in driving variation in immunity in complex environments, and how it affects survival and reproduction in hosts and parasites.
The Soay sheep of St Kilda are a primitive breed of domestic sheep that has been intensively studied since 1985 and are naturally infected with strongyle gastrointestinal nematodes. Recently, a genome-wide association study (GWAS) found regions of the genome associated with anti-Teladorsagia circumcincta antibody expression (IgA, IgE and IgG), including a genomic region with a very large effect on IgA levels. The region occurs around 1 Megabase away from two strong candidate genes, CLEC16A and CIITA. However, it is not known if and how the region affects the expression of either of these genes. The aim of this project is to use novel genome-sequencing techniques to fine map the IgA-associated region to a higher resolution in thousands of individuals, and to untangle the molecular mechanisms and evolutionary history of this variation.
Key research objectives:
1. Conduct GWAS of IgA levels using genomic data imputed from the Ovine Infinium HD SNP chip and whole genome sequence information.
2. Use transcriptomics to identify differences in gene expression between genotypes at loci associated with IgA.
3. Determine the breed of origin of loci driving immune variation – are they ancient or recently introgressed from modern breeds?
4. Investigate signatures of contemporary and long-term selection at immune loci – can we detect selection that is cryptic at the phenotypic level?
Research Training: The project will be mostly computational and will suit students who are willing to learn and further develop bioinformatic skills. The first year includes an intensive course on population genetics, quantitative genetics and statistics which will provide a basis for the analytical work. Further training will be provided by EASTBIO workshops/symposia and Edinburgh Genomics coding and bioinformatics courses. The student will also be able to take advantage of national and international collaborative links of the supervisors in the livestock and wild genomics communities.
Fieldwork: The student will be encouraged to contribute to fieldwork to collect samples and aid the field team to learn about the ecology of the system.
Lab work: Experience in molecular lab techniques is not necessary as training will be provided.
The “Visit Website” button will take you to our Online Application checklist. Complete each step and download the checklist which will provide a list of funding options and guide you through the application process. Follow the instructions on the EASTBIO website (you will be directed here from our application checklist), ensuring you upload an EASTBIO application form and transcripts to your application, and ticking the box to request references. Your referees should upload their references using the EASTBIO reference form, in time for the 5th January deadline so please give them plenty of time to do this by applying early.
Sparks AM, K Watt, R Sinclair, JG Pilkington, JM Pemberton, TN McNeilly, DH Nussey, SE Johnston (2019) The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries). bioRxiv 628271; doi: https://doi.org/10.1101/628271
Feulner PGD, J Gratten, JW. Kijas, PM Visscher, JM. Pemberton,J Slate (2013)
Introgression and the fate of domesticated genes in a wild mammal population. Mol Ecol 22, 4210–4221.
How good is research at University of Edinburgh in Biological Sciences?
FTE Category A staff submitted: 109.70
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