Quantitative trait loci for variation in immune response to a Foot-and-Mouth Disease virus peptide.
BACKGROUND
Infectious disease of livestock continues to be a cause of substantial economic loss and has adverse welfare consequences in both the developing and developed world. New solutions to control disease are needed and research focused on the genetic loci determining variation in immune-related traits has the potential to deliver solutions. However, identifying selectable markers and the causal genes involved in disease resistance and vaccine response is not straightforward. The aims of this study were to locate regions of the bovine genome that control the immune response post immunisation. 195 F2 and backcross Holstein Charolais cattle were immunised with a 40-mer peptide derived from foot-and-mouth disease virus (FMDV). T cell and antibody (IgG1 and IgG2) responses were measured at several time points post immunisation. All experimental animals (F0, F1 and F2, n = 982) were genotyped with 165 microsatellite markers for the genome scan.


RESULTS
Considerable variability in the immune responses across time was observed and sire, dam and age had significant effects on responses at specific time points. There were significant correlations within traits across time, and between IgG1 and IgG2 traits, also some weak correlations were detected between T cell and IgG2 responses. The whole genome scan detected 77 quantitative trait loci (QTL), on 22 chromosomes, including clusters of QTL on BTA 4, 5, 6, 20, 23 and 25. Two QTL reached 5% genome wide significance (on BTA 6 and 24) and one on BTA 20 reached 1% genome wide significance.


CONCLUSIONS
A proportion of the variance in the T cell and antibody response post immunisation with an FDMV peptide has a genetic component. Even though the antigen was relatively simple, the humoral and cell mediated responses were clearly under complex genetic control, with the majority of QTL located outside the MHC locus. The results suggest that there may be specific genes or loci that impact on variation in both the primary and secondary immune responses, whereas other loci may be specifically important for early or later phases of the immune response. Future fine mapping of the QTL clusters identified has the potential to reveal the causal variations underlying the variation in immune response observed.
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin Biocentre, Roslin, Midlothian, EH25 9PS, UK. richard.leach@roslin.ed.ac.uk
Richard J
RJ
Leach
Susan C
SC
Craigmile
Sara A
SA
Knott
John L
JL
Williams
Elizabeth J
EJ
Glass
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology*; D002417:Cattle / Q000235:genetics*; D005260:Female; D005536:Foot-and-Mouth Disease / Q000235:genetics* / Q000276:immunology*; D029544:Foot-and-Mouth Disease Virus / Q000276:immunology; D005838:Genotype; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D018895:Microsatellite Repeats; D010446:Peptide Fragments / Q000276:immunology*; D040641:Quantitative Trait Loci; D013601:T-Lymphocytes / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; C094837:FMDV 15 peptide; D007074:Immunoglobulin G; D010446:Peptide Fragments; D014765:Viral Vaccines