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Professor Jim Kaufman

Abstract:

The major histocompatibility complex (MHC) is the genetic region with the most associations with disease in humans, many due to highly polymorphic class I and class II genes involved in adaptive immunity. Other genes in the MHC are involved in regulation and innate immunity, including cell-surface molecules called butyrophilins, which recently have been associated with various autoimmune diseases (Abeler-Dorner et al 2011 Trends Immunol). The closest relatives in chickens are the BG genes, which are extremely polymorphic and associated with resistance to certain viral diseases, including the economically-important Marek’s disease, caused by an oncogenic herpesvirus (Goto et al 2010 PNAS).  We discovered, sequenced and ordered all 14 BG genes of a single haplotype, determined their cell/tissue distribution, and compared them to other haplotypes (Salomonsen et al, in revision for PLoS Genetics). We found that individual BG genes have very specific expression patterns, but altogether they have a wide tissue distribution. Comparison between haplotypes shows that the BG multigene family is undergoing extremely rapid expansion and contraction, leading to hybrid genes and copy number variation. We have expressed the extracellular domains of BG genes as Fc-fusion proteins, in order to produce specific monoclonal antibodies, search for ligands and use in functional assays. We will express the long cytoplasmic tails of BG genes for use in interaction assays. In doing so, we hope to discover and then examine in detail the biological roles of individual BG genes, in particular how they are involved in resistance to infectious pathogens.

References:

  1. Abeler-Dorner et al. 2011. Butyrophilins: an emerging family of immune regulators.Trends Immunol 33: 34-41  
  2. Goto et al. 2009. BG1 has a major role in MHC-linked resistance to malignant lymphoma in the chicken. PNAS 106: 16740-5  
  3. Salomonsen et al. 2014. Sequence of a complete BG haplotype shows two gene lineages with specific expression patterns and dynamic expansion and contraction. PLoS Genetics, in revision