SINGLE-STRAND CONFORMATION ANALYSIS OF 2 GENES CONTAINED WITHIN THE FIRST INTRON OF THE NEUROFIBROMATOSIS TYPE-I GENE IN PATIENTS WITH MULTIPLE-SCLEROSIS

Single strand conformation analysis has become the most widely used te chnique to screen large numbers of DNA samples for unknown mutations w hich may contribute to genetic susceptibility to disease, The method r elies on the electrophoretic migration of a single strand of nucleic a cid in a polyacrylamide gel being dependent on its conformation which is in turn dependent on its sequence, We have examined two closely rel ated genes present in the first intron of the neurofibromatosis type I gene-the oligodendrocyte myelin glycoprotein (OMGP) gene and the ecot ropic viral integration 2A (EVI2A) gene-in 36 patients with multiple s clerosis (MS) and 36 healthy controls, A single mutation was found in the OMGP gene which resulted in an amino-acid change of glycine to asp artic acid. This occurred in identical proportions (16.6%) in MS patie nts and controls. Two rare mutations were found in the EVI2A gene, one resulting in an arginine substituting for a glutamine (one control an d one patient), the other in the replacement of a glycine with serine (one control only). A third common polymorphism was seen in 5'-untrans lated region of the EVI2A gene, with 65% of patients and controls show ing a T-->C transition in either a heterozygous or a homozygous form, This makes it unlikely that either of these genes is involved in genet ic susceptibility to MS, but regions of these genes outside of the exo nic sequences have not been examined.