الفهرس 
Introduction and Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
This study includes four sections: the first part is based on a case with compound heterozygous mutations (R737H and R112C with 0.17% and 81% recombination activity), so R112C’s recombination activity is near that of the wild type. Given that RAG mutations are autosomal recessive and the patient’s mother has no symptoms with only R737H in one allele, it is interesting that when the R737H and R112C mutations are present together, immunodeficiency develops. That is unexpected because it was anticipated that the patient with the compound heterozygous mutations would have a phenotype that was near normal. As a result, the R112C mutation is apparently having a higher impact than would be predicted by the recombination assay. We found that the co-existence of both mutations lowers the recombination activity of R112C, and this is the cause of the development of immunodeficiency in the patient.
The second is a practical part conducted to assess RAG involvement in patients with chronic myeloid leukaemia. We found a significant increase in RAG1, RAG2, and DNTT levels compared to healthy controls. The third is an in-silico analysis of some RAG mutations found as heterozygous compound mutations in patients with primary immunodeficiencies. We compared the usage of Pymol, a protein remodelling programme, and the recombination assays conducted in the laboratories in detecting the more damaging mutation to be corrected via Gene therapy. We found no correlation between Pymol MatchAlign scores and the recombination assay scores. The fourth is a data analysis project that tested the hypothesis that the origin of RAG1 was a RAG transposon, which immigrated to the vertebrate genome comparatively late and affected the mutational pattern of the gene. Thus, the frequency of methylation-mediated mutations in RAG1 was significantly higher than in RAG2 and the whole genome.
In conclusion, investigation of the recombination activity of both R112C and R737H mutations revealed that the co-existence of both mutations resulted in medium recombination activity. Assessment of RAG1, RAG2 and DNTT expression levels in CML patients showed a high significant increase compared to controls and a positive correlation between RAG1 and BCR/ABL levels. Comparison of Pymol results and recombination activity obtained from recombination assays showed no correlation. The origin of RAG1 as a RAG transposon may elucidate the relatively high frequency of CpG methylation-mediated mutagenesis.