engleski

CDGs & CGDs ; - do the share the same mutations?

Glycosylation, the most abundant and the most diverse posttranslational modification affects structure and function of many glycoproteins, thus controlling various biological processes including adhesion, immune reactions and cancerogenesis. Changes in glycan structures are associated with many medicinal problems such as heart disease, cancer and degenerative diseases although in many cases it is not known whether they are cause or consequence of the disease. The process of glycan biosynthesis involves several hundreds of gene products – transporters and enzymes. Some of mutations and polymorphisms of the genes encoding them (e.g. R141H mutation of PMM2 gene encoding phosphomannomutase, and Y131H mutation and polymorphism F304S of ALG6 gene encoding  1, 3glucosyl transferase), when present in homozygous form cause congenital disorders of glycosylation (CDG Ia and CDG Ic, respectively). Surprisingly, in contrary to the very low incidence of CDG Ia and Ic, the frequency of the mutations in heterozygous form is relatively high in healthy population. Causes and consequences of the high frequency of these mutations are unknown, but the most likely explanation for these prevalent glycosylation-compromising mutations is that they confer some advantage over full glycosylation. Complex genetic disorders (CGD), such as already mentioned cardiovascular diseases, tumors and degenerative diseases represent the major cause of death in Western civilization. In order to develop novel therapies and diagnostic tools, scientists seek to identify all genetic factors contributing occurrence and development of these diseases. The most promising approach for dealing such complex, demanding and challenging task is forming biobanks and undertake large-scale research projects that will enable multilateral dealing with the problem. The aim of our part of the project is to determine correlation between mentioned high frequency mutations and pathogeneses of certain chronic and degenerative diseases and tumors. Single strand conformation polymorphism (SSCP) analysis will be used to detect mutations in PMM2 and ALG6 genes. The identity of detected mutations will be confirmed by DNA sequencing.

Congenital disorders of glycosylation; complex genetic diseases

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