Linkage and association between insulin-dependent diabetes mellitus (IDDM) susceptibility and markers near the glucokinase gene on chromosome 7
| Autor: | Graeme I. Bell, Patrick Concannon, Neil Risch, Richard S. Spielman, Rachel E. Rowe, Beth Wapelhorst |
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| Rok vydání: | 1995 |
| Předmět: |
Genetic Markers
Male Linkage disequilibrium medicine.medical_specialty endocrine system diseases Genetic Linkage Locus (genetics) Biology DNA Satellite Genetic linkage Internal medicine Glucokinase Genetics medicine Humans Allele Alleles Haplotype nutritional and metabolic diseases Endocrinology Diabetes Mellitus Type 1 Haplotypes Genetic marker Microsatellite Female Disease Susceptibility Chromosomes Human Pair 7 |
| Zdroj: | Nature genetics. 10(2) |
| ISSN: | 1061-4036 |
| Popis: | Insulin-dependent diabetes mellitus (IDDM) is characterized by autoimmune destruction of the insulin secreting beta-cells of the pancreas and subsequent disruption of glucose metabolism. The tendency of IDDM to cluster in families and the modest (36%) concordance rate in monozygotic twins indicates that both genetic and environmental factors contribute to IDDM susceptibility. Recent genome-wide searches using the affected sib-pair (ASP) approach have provided evidence for novel loci, in addition to HLA (IDDM1) and insulin (IDDM2), which show evidence of linkage to IDDM (P < 0.05). We have evaluated 35 microsatellite marker loci on human chromosome 7 for linkage to IDDM in 339 affected sib-pair families. Increased sharing of parental haplotypes in affected sib-pairs was detected for two microsatellite markers flanking glucokinase (GCK). Preferential transmission of alleles to affected offspring was observed at one of these marker loci, GCK3, indicating linkage disequilibrium between the marker and a disease susceptibility locus. This combination of linkage and disease association suggests that glucokinase, or a gene in the vicinity, plays an important part in IDDM susceptibility. |
| Databáze: | OpenAIRE |
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