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• W2024174331 abstract "The master player in the transcriptional regulation of major histocompatibility (MHC) class II genes is a factor known as the MHC class II transactivator (CIITA). In this study we searched for polymorphisms in the 5′ and 3′ ends of the human CIITA gene to assess whether or not there is an association between alleles of this gene and multiple sclerosis (MS). Polymorphism screening based upon detection of single strand conformational changes (SSCP analysis) followed by sequencing revealed six single nucleotide variations, namely one in the promoter utilized by B cells and five in the 3′ untranslated region (UTR) of the gene. Determination of alleles at these polymorphic sites was facilitated by treatment of amplified DNA fragments with a panel of appropriate restriction enzymes. The distributions of CIITA alleles did not differ between MS patients and control subjects (p > 0.05). After subgrouping of the patients into relapsing-remitting MS and primary progressive MS we found that the distribution of promoter alleles in the latter of these two patient groups differed from that of healthy control subjects (p = 0.04). There was no evidence of linkage disequilibrium between the polymorphic site in the B cell specific promoter and those in the 3′ UTR. Based upon the polymorphic sites in the 3′ UTR we identified two common CIITA haplotypes which were present at similar frequencies in patients and control subjects. Assuming that susceptibility to MS depends upon type of MHC class II molecule as well as the amounts of expressed class II molecules we tested for interaction between DR15 status and CIITA alleles. No such interaction was detected. Unexpectedly, we identified an intron in the 3′ UTR of the human as well as the mouse CIITA gene. Due to the proximity of these introns to the termination codon in both the human and mouse CIITA gene, the mechanism for regulation of transcript stability known as nonsense-mediated decay is probably not involved in the posttranscriptional control of the expression of these genes. So far, the function and significance of the intron in the human and mouse CIITA genes are unknown." @default.
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• W2024174331 date "2001-04-01" @default.
• W2024174331 modified "2023-10-14" @default.
• W2024174331 title "Genetic susceptibility to multiple sclerosis: detection of polymorphic nucleotides and an intron in the 3′ untranslated region of the major histocompatibility complex class II transactivator gene" @default.
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• W2024174331 doi "https://doi.org/10.1016/s0198-8859(01)00215-4" @default.
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