Large‐scale structural variations linked to the NOTCH4 locus of the Human Major Histocompatibility Complex

The human major histocompability complex (MHC) encodes antigen‐presenting proteins and other proteins critical to the function of the the immune system. It is also the most polymorphic component of the human genome. Variations within the MHC region have been linked to both susceptibility and resistance to multiple autoimmune diseases. The objective of the present study is to determine whether the portion of the MHC linked to the NOTCH4 gene is characterized by large‐scale structural variation and if it is, whether that variation is linked to auto‐immune disease. The NCBI human genome reference sequence indicates that NOTCH4 is contained within a 450 kilobase PmeI restriction fragment. To date, this study has used polymerase chain reaction to isolate NOTCH4 specific probes from cDNA for NOTCH4. The probes will be hybridized with Southern blots of pulsed field electrophoresis gels of PmeI digested genomic DNA isolated from patients with systemic lupus erythematosus and normal controls. This will allow the observation of size variation and imply the possibility of copy number variations, insertions and/or deletion within the region and their possible role in autoimmune disease.