EASTBIO The genomic basis and evolution of immune responses in a wild mammal population.

Variation in immune responses to pathogens can have a large impact on an individual’s condition, disease resistance, survival and fecundity. If there is genetic variation in immune response within a population, then it can respond to natural or artificial selection. Much of our knowledge on the genetic basis of this trait comes from humans and livestock due to their effects on health and their economic impact on livestock breeding. However, these populations are often treated for prevalent infectious agents and/or live in controlled environmental conditions. As a result, they often fail to relationship between the genetic basis of immune response and its consequences on survival and fecundity of both hosts and parasites under natural conditions.

This PhD will investigate the genetic causes and evolutionary consequences of immune trait variation in a wild population. The Soay sheep of St Kilda (Ovis aries) are a primitive breed of domestic sheep that has been intensively studied since 1985 and are naturally infected with strongyle nematodes. Recently, a genome-wide association study (GWAS) found regions of the genome associated with anti-strongyle antibody expression (IgA, IgE and IgG), including a genomic region with a very large effect on IgA levels corresponding to two strong candidate genes, CLEC16A and CIITA. However, it is still unknown how this region affects the expression of either gene and if this genetic variation is under selection. 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 variation in immune response.

Key research objectives:

1. Conduct GWAS of IgA levels using >400K markers 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.

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