Co-Evolution of immune genes and global diversity
Release Date: 08-31-2007
Two sets of immune-related genes influence resistance to infections, complications in pregnancy, outcomes after stem cell transplantation, and susceptibility and progression for hundreds of diseases such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis, Hodgkin disease, tuberculosis, malaria, and AIDS. These genetic systems the human leukocyte antigen (HLA) genes and the killer cell immunoglobulin-like receptor (KIR) genes, which reside on different chromosomes interact to help coordinate our immune responses.
Increasing our knowledge of population-level variation in the HLA and KIR region is critical to the study of evolutionary patterns, identification of selection events, evaluation of associations with disease, research on vaccine design (e.g., HIV), and understanding the mechanisms by which disease-predisposing genes can become relatively common in a population. Knowledge of HLA and KIR variation in different ethnic groups is also vitally important in hematopoietic stem cell transplantation (e.g., for treatment of leukemia).
Given their functional relationship in the immune response, it's hypothesized that KIR and HLA may be co-evolving in humans and indeed, the population-level evidence that is described for this epistatic interaction is compelling. This paper describes the first population-based evolutionary genetic comparison of variation at these two complex genetic systems.