Title : Molecular cloning of a human
apoC-III variant :
Thr 74----
Ala 74 mutation prevents O-glycosylation
Abstract :
- Apolipoprotein C-III ( apoC-III ) is a major protein of very low density lipoprotein ( VLDL )
- The apoC-III polypeptide contains a carbohydrate chain containing galactosamine, galactose, and sialic acid attached in O-linkage to a threonine residue at position 74
- We have cloned the apoC-III gene from a subject whose serum contained unusually high amounts of apoC-III lacking the carbohydrate moiety (C-III-0)
- DNA sequence analysis of the cloned gene revealed a single nucleotide substitution (A----G) that encodes an alanine at position 74 instead of the normal threonine
- As a result of this amino acid replacement, the mutant apoC-III polypeptide is not glycosylated
- The mutation in the apoC-III gene creates a novel AluI site that permits diagnosis of the change by Southern blotting of genomic DNA