Genetic Structure of IDDM1: Two Separate Regions in the Major Histocompatibility Complex Contribute to Susceptibility or Protection
| Autor: | B. Van der Auwera, F. K. Gorus, Frans Schuit, Albert Naipal, Marius J. Giphart, Bart O. Roep, P. De Knijf, Payman Hanifi Moghaddam |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Genetics
Linkage disequilibrium endocrine system diseases Endocrinology Diabetes and Metabolism Haplotype nutritional and metabolic diseases Locus (genetics) Human leukocyte antigen Biology Major histocompatibility complex Genetic determinism immune system diseases Genotype Internal Medicine biology.protein Microsatellite |
| Zdroj: | Diabetes. 47:263-269 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | We analyzed 11 markers in the IDDM1 region in 120 IDDM patients and 83 healthy control subjects who were fully matched for the highest risk HLADQA1*O3O1-DQB1*O3O2/DQA1*O5O1-DQB1*O2O1 genotype. Our study provides strong evidence that two regions in the major histocompatibility complex contribute to IDDM susceptibility or protection. First, despite selection for highest IDDM-associated risk DQ genotypes, this region displays extensive linkage disequilibrium (LD) differences between IDDM patients and control subjects. A second critical region was mapped around the microsatellite locus D6S273 centromeric of TNF, and it is ∼200 kb in size. LD analysis shows that “diabetogenic haplotypes” may have resulted from a recombination telomeric of D6S1014 in the region of D6S273 and TNFa. Haplotype analysis using HLA and microsatellite loci refines IDDM risk assessment in carriers of the HLA-DQ highest risk genotype. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|