New polymorphic microsatellite markers in the human MHC class III region

The human major histocompatibility complex (MHC) class LII region spanning approximately 760 kb is characterized by a remarkably high gene density wit h 59 expressed genes (one gene every 12.9 kb). Recently, susceptibility loc i to numerous diseases, such as Graves disease, Crohn disease, and SLE have been suggested to be localized to this region, as assessed by associations mainly with genetic polymorphisms of TNF and TNF-linked microsatellite loc i. However, it has been difficult to precisely localize these susceptibilit y loci to a single gene due to a paucity to date of polymorphic markers in the HLA class III region. To facilitate disease mapping within this region, we have analyzed 2 similar to5 bases short tandem repeats (microsatellites ) in this region. A total of 297 microsatellites were identified from the g enomic sequence, consisting of 69 di-, 62 tri-, 107 tetra-, and 59 penta-nu cleotide repeats. It was noted that among them as many as 17 microsatellite s were located within the coding sequence of expressed genes (NOTCH4, PBX2, RAGE, G16, LPAAT, PPT2, TNXB, P450-CYP21B, G9a, HSP70-2, HSP70-1, HSP-hom, MuTSH5 and BAT2), Eight microsatellite repeats were collected as polymorph ic markers due to their high number of alleles (11.9 on average) as well as their high polymorphic content value (PIC) (0.63). By combining the 38 and the 22 polymorphic microsatellites we have previously collected in the HLA class I and class II regions, respectively we have now established a total of 68 novel genetic markers which are uniformly interspersed with a high d ensity of one every 63.3 kb throughout the HLA region. This collection of p olymorphic microsatellites will enable us to search for the location of any disease susceptible loci within the HLA region by association analysis.