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Type 1 diabetes : evidence for susceptibility loci from four genome-wide linkage scans in 1,435 multiplex familiesConcannon, Patrick ...Type 1 diabetes is a common, multifactorial disease with strong familial clustering (genetic risk ratio (lambdasl approx. 15). Approximately 40% of thefamilial aggregation of type 1 diabetes can be ... attributed to allelic variation ofHLA loci in the major histocompatibility complex on chromosome 6p21 (locus-specific lambdas approx. 3). Three other disease susceptibility loci have been clearly demonstrated based on their direct effect on risk, INS (chromosome 11p15, allelic odds ratio (OR) approx. 1.9), CTLA4 (chromosome 2q33, allelic OR approx. 1.2), and PTPN22 (chromosome 1p13, allelic OR qpprox.1.7). However, a large proportion of type 1 diabetes clustering remainsunexplained. We report here on a combined link-age analysis of four datasets, three previously published genome scans, and one new genome scan of 254 families, which were consolidated through aninternational consortium for type 1 diabetes genetic studies (www.t1dgc.org) and provided a total sample of1,435 families with 1,636 affected sibpairs. In addition to the HLA region (nominal P=2.0 x 10-52), nine non-HLA-linked regions showed some evidence of linkage to type 1 diabetes (nominal P<0.01), including three at (or near) genome-wide significance (P<0.05):2q31-q33, 10p14-q11, and 16q22-q24. In addition, after taking into account the linkage at the 6p21 (HLA) region, there was evidence supporting linkage for the 6q21 region (empiric P<10-4). More than 80% of the genome could be excluded as harboring type 1 diabetes susceptibility genes of modest effect (lambda2 >= 1.3) that could be detected by linkage. This study represents one of the largest linkage studies ever performed for any common disease. The results demonstrate some consistency emerging for the existence of susceptibility loci on chromosomes 2q31-q33, 6q21, 10p14-q11, and 16q22-q24 but diminished support for some previously reported locations.Vir: Diabetes. - ISSN 0012-1797 (Letn. 54, 2005, str. 2995-3001)Vrsta gradiva - članek, sestavni delLeto - 2005Jezik - angleškiCOBISS.SI-ID - 20656089
Avtor
Concannon, Patrick |
Erlich, Henry A. |
Julier, Cecile |
Morahan, Grant |
Nerup, Jørn |
Pociot, Flemming |
Todd, John A. |
Rich, Stephen S. |
Avbelj Stefanija, Magdalena, 1974-2024 |
Battelino, Tadej
Teme
Genetic Markers |
Linkage (Genetics) |
Genetics |
Hla Antigens |
Chromosome Mapping |
Chromosomes, Human, Pair 10 |
Chromosomes, Human, Pair 16 |
Chromosomes, Human, Pair 2 |
Chromosomes, Human, Pair 6 |
Chromosomes, Human, Pair 1 |
Family |
Genetski označevalci |
HLA antigeni |
Kromosomi človeški, par 10 |
Kromosomska karta |
Vezava (genetika) |
Družina |
Kromosomi človeški, par 1 |
Kromosomi človeški, par 16 |
Kromosomi človeški, par 2 |
Kromosomi človeški, par 6
Vnos na polico
Trajna povezava
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Concannon, Patrick | |
Erlich, Henry A. | |
Julier, Cecile | |
Morahan, Grant | |
Nerup, Jørn | |
Pociot, Flemming | |
Todd, John A. | |
Rich, Stephen S. | |
Avbelj Stefanija, Magdalena, 1974-2024 | 23435 |
Battelino, Tadej | 13023 |
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