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 (FBP) gene were designed and used to isolate a cosmid clone. Physical mapping of the FBP cosmid by FISH, and genetic mapping of an associated GA repeat polymorphism (PIC = 0.35), located the liver FBP gene to chromosome 9q22.3 with no recombination between FBP and the index markers D9S196 (Zmax = 13.2), D9S280 (Zmax = 11.7), D9S287 (Zmax = 15.6), and D9S176 (Zmax = 14.4). Amplification using FBP exon-specific primers with a YAC contig from this region of chromosome 9 further refined the placement of FBP genomic sequences to an approximately 1.7-cM region flanked by D9S280 and D9S287, near the gene for Fanconi anemia group C. Precise localization of the FBP gene enabled evaluation of FBP as a candidate gene for maturity-onset diabetes of the young (MODY) and non-insulin-dependent diabetes (NIDDM) in both Caucasian and African-American families, using the highly informative markers D9S287 and D9S176. Although FBP is a rate-limiting enzyme in gluconeogenesis, using both parametric and nonparametric analysis there was no evidence for linkage of FBP to diabetes in these families.
Rothschild
C B
CB
Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
Freedman
B I
BI
Hodge
R
R
Rao
P N
PN
Pettenati
M J
MJ
Anderson
R A
RA
Akots
G
G
Qadri
A
A
Roh
B
B
Fajans
S S
SS
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005091:Exons; D005199:Fanconi Anemia / Q000235:genetics; D005260:Female; D006597:Fructose-Bisphosphatase / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D018149:Glucose Intolerance / Q000235:genetics; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic; D012091:Repetitive Sequences, Nucleic Acid
D017931:DNA Primers; D005819:Genetic Markers; D006597:Fructose-Bisphosphatase