title: Variation in European harbour seal immune response genes and susceptibility to phocine distemper virus (PDV).
abstract: Phocine distemper virus (PDV) has caused two mass mortalities of European harbour seals (Phoca vitulina) in recent decades. Levels of mortality varied considerably among European populations in both the 1988 and 2002 epidemics, with higher mortality in continental European populations in comparison to UK populations. High levels of genetic differentiation at neutral makers among seal populations allow for the possibility that there could be potential genetic differences at functional loci that may account for some of the variation in mortality. Recent genome sequencing of carnivore species and development of genomic tools have now made it possible to explore the possible contribution of variation in candidate genes from harbour seals in relation to the differential mortality patterns. We assessed variation in eight genes (CD46, IFNG, IL4, IL8, IL10, RARa, SLAM and TLR2) encoding key proteins involved in host cellular interactions with Morbilliviruses and the relationship of variants to disease status. This work constitutes the first genetic association study for Morbillivirus disease susceptibility in a non-model organism, and for a natural mortality event. We found no variation in harbour seals from across Europe in the protein coding domains of the viral receptors SLAM and CD46, but SNPs were present in SLAM intron 2. SNPs were also present in IL8 p2 and RARa exon 1. There was no significant association of SLAM or RARa polymorphisms with disease status implying no role of these genes in determining resistance to PDV induced mortality, that could be detected with the available samples and the small number of polymorphisms indentified. However there was significant differentiation of allele frequencies among populations. PDV and other morbilliviruses are important models for wildlife epidemiology, host switches and viral evolution. Despite a negative result in this case, full sequencing of pinniped and other 'non-model' carnivore genomes will help in refining understanding the role of host genetics in disease susceptibility for these viruses.
authors.affiliation: Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: McCarthy
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Shaw
authors.forename: Paul D
authors.initials: PD
authors.lastname: Jepson
authors.forename: Sophie M J M
authors.initials: SM
authors.lastname: Brasseur
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Reijnders
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Goodman
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D004216:Distemper / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000821:virology; D018104:Distemper Virus, Phocine / Q000472:pathogenicity*; D005060:Europe / Q000453:epidemiology; D005802:Genes, MHC Class II; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005828:Genetics, Population; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D046049:Phoca / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
chemical_list: D015703:Antigens, CD; D017931:DNA Primers; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1