Large transcripts and sequence from a polymorphic 170 kb MHC region implicated in susceptibility to autoimmune disease.

Abstract

We have used the novel strategy of overlapping yeast artificial chromosome (YAC) clones to localize a series of new transcripts within a 170 kb region of the human major histocompatibility complex (MHC), containing genes likely to be of importance for disease susceptibility. Using cloned genomic probes we have further localized these transcripts to a region 15 kilobases (kb) centromeric of HLA-B. In the liver there are at least four transcripts ranging in size between 7.5 kb and 3.4 kb, while in the lung two transcripts of 5.8 kb and 4.2 kb are detected. The possible implications of these transcripts for autoimmune disease are discussed, given that they are located in a region previously shown to be of importance for susceptibility to insulin-dependent diabetes mellitus and myasthenia gravis. Furthermore, we conclude that YACs as large as 360 kb are able to be used as probes to identify new transcripts and that the MHC region between HLA-B and BAT1 is the site of a large multiply spliced gene, provisionally designated PERB6.