Linkage of type 2 diabetes to the glucokinase gene.
Maturity-onset diabetes of the young (MODY) is a subtype of type 2 diabetes that presents from the second decade and has an autosomal dominant mode of inheritance. We have investigated the glucokinase gene, a candidate gene for diabetes, in two MODY pedigrees. In a large 5-generation pedigree (BX) with 15 diabetic members, use of a microsatellite polymorphism revealed linkage of diabetes to the glucokinase locus on chromosome 7p. A peak lod score of 4.60 was obtained at a recombination fraction (theta) of zero. This finding suggests that a defective glucokinase gene contributes to the diabetes phenotype in this pedigree. This is not universal in MODY since linkage to the glucokinase locus was excluded in a second pedigree M (lod score = -7.36 at theta = 0). The affected members in pedigree BX were diagnosed either when young (in pregnancy or on screening) or when they presented symptomatically in middle and old age; most of them were treated by diet alone. Defects in the glucokinase gene may play an important part in the pathogenesis of type 2 diabetes.
Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford, UK.
A T
AT
Hattersley
R C
RC
Turner
M A
MA
Permutt
P
P
Patel
Y
Y
Tanizawa
K C
KC
Chiu
S
S
O'Rahilly
P J
PJ
Watkins
J S
JS
Wainscoat
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D004247:DNA; D003924:Diabetes Mellitus, Type 2 / Q000145:classification / Q000235:genetics* / Q000503:physiopathology; D005215:Fasting; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D005820:Genetic Testing; D005941:Glucokinase / Q000235:genetics* / Q000502:physiology; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007515:Islets of Langerhans / Q000503:physiopathology; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic
D001786:Blood Glucose; D009841:Oligonucleotides; D004247:DNA; D005941:Glucokinase