FRUCTOSE-1,6-BISPHOSPHATASE - GENETIC AND PHYSICAL MAPPING TO HUMAN-CHROMOSOME 9Q22.3 AND EVALUATION IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

PCR primers specific to the human liver fructose-1,6-bisphosphatase (F BP) gene were designed and used to isolate a cosmid clone. Physical ma pping of the FBP cosmid by FISH, and genetic mapping of an associated GA repeat polymorphism (PIC = 0.35), located the liver FBP gene to chr omosome 9q22.3 with no recombination between FBP and the index markers D9S196 (Z(max) = 13.2), D9S280 (Z(max) = 11.7), D95287 (Z(max) = 15.6 ), and D9S176 (Z(max) = 14.4). Amplification using FBP exon-specific p rimers with a YAC contig from this region of chromosome 9 further refi ned the placement of FBP genomic sequences to an approximately 1.7-cM region flanked by D9S280 and D95287, near the gene for Fanconi anemia group C. Precise localization of the FBP gene enabled evaluation of FB P as a candidate gene for maturity-onset diabetes of the young (MODY) and non-insulin-dependent diabetes (NIDDM) in both Caucasian and Afric an-American families, using the highly informative markers D95287 and D9S176. Although FBP is a rate-limiting enzyme in gluconeogenesis, usi ng both parametric and nonparametric analysis there was no evidence fo r linkage of FBP to diabetes in these families. (C) 1995 Academic Pres s, Inc.