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.
Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
C B
CB
Rothschild
B I
BI
Freedman
R
R
Hodge
P N
PN
Rao
M J
MJ
Pettenati
R A
RA
Anderson
G
G
Akots
A
A
Qadri
B
B
Roh
S S
SS
Fajans
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