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Data from: The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries)

Citation

Sparks, Alexandra et al. (2019), Data from: The genetic architecture of helminth-specific immune responses in a wild population of Soay sheep (Ovis aries), Dryad, Dataset, https://doi.org/10.5061/dryad.zgmsbcc6f

Abstract

Much of our knowledge of the drivers of immune variation, and how these responses vary over time, comes from humans, domesticated livestock or laboratory organisms. While the genetic basis of variation in immune responses have been investigated in these systems, there is a poor understanding of how genetic variation influences immunity in natural, untreated populations living in complex environments. Here, we examine the genetic architecture of variation in immune traits in the Soay sheep of St Kilda, an unmanaged population of sheep infected with strongyle gastrointestinal nematodes. We assayed IgA, IgE and IgG antibodies against the prevalent nematode Teladorsagia circumcincta in the blood plasma of > 3,000 sheep collected over 26 years. Antibody levels were significantly heritable (h2 = 0.21 to 0.57) and highly stable over an individual’s lifespan. IgA levels were strongly associated with a region on chromosome 24 explaining 21.1% and 24.5% of heritable variation in lambs and adults, respectively. This region was adjacent to two candidate loci, Class II Major Histocompatibility Complex Transactivator (CIITA) and C-Type Lectin Domain Containing 16A (CLEC16A). Lamb IgA levels were also associated with the immunoglobulin heavy constant loci (IGH) complex, and adult IgE levels and lamb IgA and IgG levels were associated with the major histocompatibility complex (MHC). This study provides evidence of high heritability of a complex immunological trait under natural conditions and provides the first evidence from a genome-wide study that large effect genes located outside the MHC region exist for immune traits in the wild.

Methods

This data was collected as part of the long term individual based study on the Soay sheep of St Kilda in Scotland. Details of dataset processing is provided in the usage notes and READ ME associated with this repository.

Usage Notes

#~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~#

SOAY SHEEP PROJECT DATA REUSE:

The attached file(s) contain data derived from the long term field project
monitoring individual Soay sheep on St Kilda and their environment.  This is a
request to please let us know if you use them.  Several people have spent the
best part of their careers collecting the data.  If you plan to analyse the
data, there are a number of reasons why it would be very helpful if you could
contact Josephine Pemberton (j.pemberton@ed.ac.uk) before doing so.

[NB. If you are interested in analysing the detailed project data in any depth 
you may find it helpful to have our full relational database rather than the
file(s) available here.  If so, then we have a simple process for bringing you
onto the project as a collaborator.]

1) The data can be subject to change due to updates in the pedigree, merging of
records, occasional errors and so on.

2) The data are complex and workers who do not know the study system may
benefit from advice when interpreting it.

3) At any one time a number of people within the existing project collaboration
are analysing data from this project. Someone else may already be conducting
the analysis you have in mind and it is desirable to prevent duplication of
effort.

4) In order to maintain funding for the project(s), every few years we have to
write proposals for original analyses to funding agencies. It is therefore very
helpful for those running the project to know what data analyses are in
progress.

5) Sheep identifiers may vary relative to other data archives from papers using
the Soay sheep data.

#~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~#

DATA DESCRIPTION:

These data are related to the manuscript:

The genetic architecture of helminth-specific immune responses in a wild
population of Soay sheep (Ovis aries).

A. M. Sparks, K. Watt, R. Sinclair, J. G. Pilkington, J. M. Pemberton, 
T. N. McNeilly, D. H. Nussey, S. E. Johnston

For questions related specifically to this dataset, please contact Susan
Johnston (Susan.Johnston@ed.ac.uk) or Alexandra Sparks (A.M.Sparks@leeds.ac.uk).

All analysis scripts are provided at https://github.com/sejlab/Soay_Immune_GWAS 
and use the same directory structure as outlined in the file paths below. 

Scripts are run in the following order:

1.1_BeastAnModGRM070218.R
1.2_Format_Results.R
1.3_BEAST_Genetic_Correlations.R
1.4_Parse_Genetic_Correlations.R
brute_GWAS/2_BEAST_GWAS_Prepare.R 
brute_GWAS/2_BEAST_GWAS_Run.R
brute_GWAS_log_Lambs/2_BEAST_GWAS_Prepare.R 
brute_GWAS_log_Lambs/2_BEAST_GWAS_Run.R
2.2.2_BEAST_GWAS_Parse_BiomaRt_log_Lambs.R
2.2_BEAST_GWAS_Parse_BiomaRt.R
2.3_Reparse_and_format_gene_GO_tables.R
3.1_Imputation_in_Sig_Regions.R
3.1_Imputation_in_Sig_Regions_log_Lambs.R
alphaimpute/3_Imputed_GWAS_Prepare.R
alphaimpute/3_Imputed_GWAS_Run.R
alphaimpute/3_Imputed_GWAS_Run_log_Lambs.R
3.2_Parse_Genotypes_Prepare_for_GWAS.R
3.2_Parse_Genotypes_Prepare_for_GWAS_log_Lambs.R
3.3_Parse_Alphaimpute_GWAS.R
3.3_Parse_Alphaimpute_GWAS_log_Lambs.R
4_Examine_GWAS_Results_LD_Genes.R 
5_Variance_Attributed_to_Regions.R
6_BiomaRt_SNP_functions.R
6_BLAST_MHC_with_Rambouillet_Genome.R
7_Sex_Specific_Effects_v1.R
7_SNP_Effects.R

The data files used are as follows:

* data/20181107_BEAST_data_formatted.RData

This is an .RData file containing the data frame `pedigree` (ID, MOTHER, FATHER
information) and data frame `BEASTX` which contains individual immune phenotype
measures.
[N.B. All .RData files can be read into R using the command: load("FILENAME")]


* data/20181107_Genabel_Data.RData

This is an .RData file containing the 50K genotype data in GenABEL format after
quality control (N.B. requires R v3.4.3 and the R library GenABEL v1.8-0).

* data/20181107_SoayGRM.Rdata

This is an .RData file containing the genomic relatedness matrix used for
estimating trait heritability.

* data/Ovis_aries.Oar_v3.1.94.genes.txt

This is a text file containing the gene information for Ovis aries, as obtained
from Ensembl.

* data/20180209_SoayPlates1-83.bed/.bim/.fam

These are the PLINK files containing the 50K genotype data after quality 
control.

* data/20180209_SoayPlates1-83.bed/.bim/.fam

These are the PLINK files containing the 50K genotype data after quality 
control.

* data/20140214_SheepHD_QC1_Polym.bed/.bim/.fam

These are the PLINK files containing the HD genotype data after quality control.


 

Funding

Natural Environment Research Council,

European Research Council, Award: EC 250098 WEG

Biotechnology and Biological Sciences Research Council, Award: BB/H021868/1

Scottish Government,

Medical Research Council, Award: 1369297

Royal Society, Award: UF150448