Linkage Disequilibrium Between Microsatellite Markers Extends Beyond 1 cM on Chromosome 20 in Finns
Karen L. MohlkeGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USAEthan M. LangeUniversity of MichiganTimo T. ValleGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandSoumitra GhoshGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandVictoria L. MagnusonGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandKaisa SilanderGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandRichard M. WatanabeGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandPeter S. ChinesGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandRichard N. BergmanGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandJaakko TuomilehtoGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandFrancis S. CollinsGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, FinlandMichael BoehnkeGenetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA;
2University of Michigan, School of Public Health, Department of Biostatistics, Ann Arbor, Michigan 48109, USA;
3National Public Health Institute, Department of Epidemiology and Health Promotion, Diabetes and Genetic Epidemiology Unit,
Helsinki, Finland;
4Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California
90033, USA;
5Department of Public Health, University of Helsinki, Helsinki, Finland
2001en
ABI
Аннотация
Linkage disequilibrium (LD) is a proven tool for evaluating population structure and localizing genes for monogenic disorders. LD-based methods may also help localize genes for complex traits. We evaluated marker-marker LD using 43 microsatellite markers spanning chromosome 20 with an average density of 2.3 cM. We studied 837 individuals affected with type 2 diabetes and 386 mostly unaffected spouse controls. A test of homogeneity between the affected individuals and their spouses showed no difference, allowing the 1223 individuals to be analyzed together. Significant (P < 0.01) LD was observed using a likelihood ratio test in all (11/11) marker pairs within 1 cM, 78% (25/32) of pairs 1-3 cM apart, and 39% (7/18) of pairs 3-4 cM apart, but for only 12 of 842 pairs more than 4 cM apart. We used the human genome project working draft sequence to estimate kilobase (kb) intermarker distances, and observed highly significant LD (P < 10(-10)) for all six marker pairs up to 350 kb apart, although the correlation of LD with cM is slightly better than the correlation with megabases. These data suggest that microsatellites present at 1-cM density are sufficient to observe marker-marker LD in the Finnish population.
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