engleski

Genomics and epigenomics of the human glycome

The majority of all proteins are glycosylated and glycans have numerous important structural, functional and regulatory roles in various physiological processes. While structure of the polypeptide part of a glycoprotein is defined by the sequence of nucleotides in the corresponding gene, structure of a glycan part results from dynamic interactions between hundreds of genes, their protein products and environmental factors. The composition of the glycome attached to an individual protein, or to a complex mixture of proteins, like human plasma, is stable within an individual, but very variable between individuals. This variability stems from numerous common genetic polymorphisms reflecting in changes in the complex biosynthetic pathway of glycans, but also from the interaction with the environment. Environment can affect glycan biosynthesis at the level of substrate availability, regulation of enzyme activity and/or hormonal signals, but also through gene- environment interactions. Epigenetics provides a molecular basis how the environment can modify phenotype of an individual. The epigenetic information (DNA methylation pattern and histone code) is especially vulnerable to environmental effects in the early intrauterine and neo-natal development and many common late- onset diseases take root already at that time. The evidences showing the link between epigenetics and glycosylation are accumulating. Recent progress in high-throughput glycomics, genomics and epigenomics enabled first epidemiological and genome-wide association studies of the glycome, which are presented in this mini-review.

Glycosylation ; Glycome ; Genome-wide association study ; Epigenetics ; Gene-environment interactions

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