Complex disease: Ups and downs at the MHC

The human major histocompatibility complex (MHC) is an unusual part of the genome. This ~3.5 Mb region has the highest density of genes in the human genome (the majority of which have fundamental roles in immunity), as well as high levels of variation and extensive linkage disequilibrium. It is also the region that has the most identified associations with diseases, many (but not all) of which are immunity related. However, identifying causal variants in the MHC is uniquely challenging because the association may be with an extended haplotype that spans hundreds of genes. A transcriptomic study now offers hope of progress in MHC disease genetics.