Human genetic deficits in glycan formation

Glycans are associated with most proteins found in secretions and on the surface of mammalian cells. Glycans of secreted glycoproteins affect many protein properties such as solubility, stability, protease sensitivity, and polarity, while glycans on cell surface glycoproteins are involved in various cellular functions including cell-cell and cell-matrix interactions during embryogenesis, immune reactions, and tumor development. Recent advances in human genomic research together with newly developed and sensitive methods for the analysis of glycan structures have elucidated the etiology of a growing number of human genetic diseases with aberrant glycan formation. Among these diseases, defects of protein N-glycosylation and O-mannosylation are reviewed here. The former is relatively common and the latter is rather uncommon. Both types of defects lead to severe abnormalities, which indicate the importance of glycosylation. Sequencing of the human genome is essentially complete and now glycobiology becomes an important area of postgenomic research. Glycobiology is expected to produce remarkable advances in the understanding and treatment of certain genetic diseases.