Disease relevance of IDDM8

• Affected-sib-pair mapping of a novel susceptibility gene to insulin-dependent diabetes mellitus (IDDM8) on chromosome 6q25-q27 [1].
• CONCLUSION: These results support the hypothesis that there are autoimmune disease genes at IDDM5 and IDDM8 [2].

High impact information on IDDM8

• Although significant and consistent linkage evidence was reported for the susceptibility intervals IDDM8 (on human chromosome 6q27), IDDM4 (on 11q) and IDDM5 (on 6q25), evidence for most other intervals varies in different data sets -probably due to a weak effect of the disease genes, genetic heterogeneity or random variation [3].
• Exploratory analyses, taking into account the presence of specific high-risk HLA genotypes or affected sibs' ages at disease onset, provided evidence of linkage at several additional sites, including the putative IDDM8 locus on chromosome 6q27 [4].
• When cumulated with previously published results, with overlapping families removed, the affected-sib-pair tests had a significance of P = .0001 for IDDM5 and P = .00004 for IDDM8 [5].
• The two regions still showed positive evidence of linkage, most notably the proterminal region, 6q27, corresponding to IDDM8 (MLS = 2.57, p = 0.0006; lambda s = 1.17) [6].
• RESULTS: With the ETDT, we found evidence for linkage disequilibrium of the marker D6S446, at IDDM8, with RA (P < 0.0001) [2].

Biological context of IDDM8

• We could not confirm linkage for IDDM5, IDDM8 and IDDM15 in our population, possibly due to population-specific differences in genetic susceptibility and/or environmental triggering factors to type 1 diabetes [7].
• A microsatellite marker allele and multiple haplotypes were associated with IDDM8, which suggests localization of this type 1 diabetes susceptibility gene to the terminal 200 kb of chromosome 6 [8].
• To examine whether IGF2R might contribute to the IDDM8 effect, we examined transmission distortion at several single nucleotide polymorphisms (SNPs) in 404 parent-offspring trios [9].

Other interactions of IDDM8

• Confirmation of three susceptibility genes to insulin-dependent diabetes mellitus: IDDM4, IDDM5 and IDDM8 [10].
• These findings suggest that the PDCD2 gene is a likely susceptibility gene for T1D within IDDM8 [11].
• We also identified additional loci that demonstrate allele sharing predominantly from one parent: IDDM8 shows a paternal origin effect, IDDM10 shows a maternal effect, and a locus on chromosome 16q demonstrates a paternal effect [12].

References