Evolutionary history of copy-number-variable locus for the low-affinity Fcγ receptor: mutation rate, autoimmune disease, and the legacy of helminth infection.

ABSTRACT: Both sequence variation and copy-number variation (CNV) of the genes encoding receptors for immunoglobulin G (Fcγ receptors) have been genetically and functionally associated with a number of autoimmune diseases. However, the molecular nature and evolutionary context of this variation is unknown. Here, we describe the structure of the CNV, estimate its mutation rate and diversity, and place it in the context of the known functional alloantigen variation of these genes. Deletion of Fcγ receptor IIIB, associated with systemic lupus erythematosus, is a result of independent nonallelic homologous recombination events with a frequency of approximately 0.1%. We also show that pathogen diversity, in particular helminth diversity, has played a critical role in shaping the functional variation at t

SUBMITTER: Machado LR 

PROVIDER: S-EPMC3370267 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature