This NIAID-funded Population Genetics project (J. Gulcher, PI, deCODE Genetics) is aimed at discovering host genes involved in immune response and adverse effects to vaccination. Specifically, the teams at deCODE, NCGR and the University of New Mexico Health Sciences Center (UNM-HSC) will collaborate to study four different populations having

1. adverse effect to smallpox vaccination,
2. clinical tuberculosis infection versus seroconversion,
3. serious influenza infections, and
4. one or more severe infections associated with encapsulated bacteria such as S. pneumoniae, H. influenzae, and N. meningitidis.

Using the Icelandic genealogy database, deCODE is identifying extended families affected in each category and carrying out genome-wide linkage and case-control association studies to map host genes. Following identification of host genes that confer substantial risk for infection or vaccine response, the UNM-HSC team will functionally validate them by testing protein and mRNA expression differences in monocyte and dendritic cells of patients with infection susceptibility versus controls, with or without in vitro pathogen exposure. NCGR (S. Kingsmore, J. van Velkinburgh, R. Langly) used its expertise in creating informatics systems and analyzing large datasets to create and update a discovery platform of linkage analysis and validation results called GEYSIR. Dr. van Velkinburgh is also seeking validation of deCODE findings using mRNA-seq.