ABSTRACT
A genome-wide scan was performed, using nonparametric linkage analyses, to find susceptibility loci for type 2 diabetes mellitus in the Dutch population. We studied 178 families from The Netherlands, who constituted 312 affected sibling pairs. The first stage of the genome scan consisted of 270 DNA markers, with an average intermarker spacing of 13 cM. Because obesity and type 2 diabetes mellitus are interrelated, the data set was stratified for the subphenotype body mass index, corrected for age and gender. This resulted in a suggestive maximum multipoint LOD score of 2.3 (single-point P value, 9.7 x 10(-4); genome-wide P value, 0.028) for the most obese 20% pedigrees of the data set, between marker loci D18S471 and D18S843. In the lowest 80% obese pedigrees, two interesting loci on chromosome 2 and 19 were found, with LOD scores of 1.5 and 1.3. We provide independent evidence that the chromosome 18p11 locus, reported earlier from a Finnish/Swedish population, is of definite interest for type 2 diabetes mellitus in connection with obesity. Subsequently, our results indicate that two novel loci may reside on chromosomes 2 and 19, with minor effects involved in the development of type 2 diabetes mellitus in the Dutch population.
Subject(s)
Chromosomes, Human, Pair 18 , Chromosomes, Human, Pair 19 , Chromosomes, Human, Pair 2 , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Aged , Diabetes Mellitus/genetics , Female , Genotype , Humans , Lod Score , Male , Middle Aged , Netherlands , Obesity/geneticsSubject(s)
ATP-Binding Cassette Transporters , Diabetes Mellitus, Type 2/genetics , Polymorphism, Restriction Fragment Length , Potassium Channels, Inwardly Rectifying , Potassium Channels/genetics , Receptors, Drug/genetics , Cohort Studies , Humans , Netherlands , Risk Factors , Sulfonylurea ReceptorsABSTRACT
In man-Chinese hamster somatic cell hybrids the segregation patterns of the loci for 25 human enzyme markers and human chromosomes were studied. The results provide evidence for the localization of the gene for adenylate kinase-1 (AK1) on chromosome 9. Since the loci for the ABO blood group (ABO), nail-patella syndrome (Np), and AK1 are known to be linked in man, the ABO:Np:AK1 linkage group may be assigned to chromosome 9.
Subject(s)
ABO Blood-Group System , Adenylate Kinase , Chromosomes, Human, 6-12 and X , Nail-Patella Syndrome/genetics , Phosphotransferases , Genetic Linkage , Humans , IsoenzymesSubject(s)
Chromosome Mapping , Chromosomes, Human, 1-3 , Fumarate Hydratase , Hydro-Lyases , Nucleotidyltransferases , Peptide Hydrolases , Phosphoglucomutase , Phosphogluconate Dehydrogenase , Phosphopyruvate Hydratase , Phosphotransferases , UTP-Glucose-1-Phosphate Uridylyltransferase , Animals , Chromosome Aberrations , Cricetinae , Genes , Humans , Hybrid CellsSubject(s)
Chromosome Aberrations , Chromosome Mapping , Chromosomes, Human, 1-3 , Enzymes , Hybrid Cells , Animals , Cell Line , Cricetinae , Humans , Hybridization, GeneticSubject(s)
Carbohydrate Epimerases , Chromosome Mapping , Hexosaminidases , Hybrid Cells/enzymology , Pyruvate Kinase , Animals , Cell Line , Cricetinae , HumansSubject(s)
Carbohydrate Epimerases , Chromosome Mapping , Genetic Linkage , Hexosaminidases , Pyruvate Kinase , Animals , Cricetinae , Humans , Hybrid CellsSubject(s)
Alanine Transaminase/biosynthesis , Chromosome Mapping , Genes , Genetic Linkage , L-Lactate Dehydrogenase/biosynthesis , Animals , Cells, Cultured , Cricetinae , Electrophoresis, Starch Gel , Erythrocytes/enzymology , Fibroblasts , Humans , Hybrid Cells/enzymology , Isoenzymes , Ketoglutaric Acids , Polymorphism, GeneticABSTRACT
In man-Chinese hamster somatic cell hybrids the segregation of the loci for 27 human enzyme markers and the species-specific surface antigens, including the HL-A histocompatibility antigens, was studied. The results show a synteny of the human loci for phosphoglucomutase 3, cytoplasmic malic enzyme, tetrameric indophenol oxidase, and HL-A. Furthermore, evidence is presented that the loci for the human species-specific antigens are distributed over several chromosomes.
