LINKAGE DISEQUILIBRIUM AND LINKAGE ANALYSIS OF THE GLUCOSE-6-PHOSPHATASE GENE

Recent studies have indicated that the four most common mutations acco unt for 78% of mutant alleles in the glucose-6-phosphatase (G6Pase) ge ne. A significant fraction of mutant alleles remain unidentified. Thus , informative polymorphic markers are necessary for linkage analysis i n carrier testing and prenatal diagnosis in families where mutations c an not be identified. The common mutations appear to be ethnic-specifi c, suggesting that the individual mutations may have a common founder. With the recent discovery of the nucleotide 1176 polymorphism, we hav e studied whether these mutations are in linkage disequilibrium with t he polymorphism. The results of polymerase chain reaction/allele-speci fic oligonucleotide analysis show that nucleotide 1176 C is in linkage disequilibrium with mutations R83 C and R83H, and with the splicing m utation 727G --> T. The 1176 T polymorphism is in linkage disequilibri um with 459insTA. A GT repeat polymorphism has also been found. Howeve r, its heterozygosity is low. The 1176 nucleotide polymorphic marker c an be used in carrier and prenatal diagnosis of GSD la families that h ave unidentified mutations and are informative for this marker.