Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/lty/Bcg genes on chromosome 1

Cornall, Richard J.; Prins, Jan–Bas; Todd, John A.; Pressey, A; DeLarato, Nicole H.; Wicker, Linda S.; Peterson, Laurence B.

doi:10.1038/353262a0

Cited by 164 publications

(73 citation statements)

References 24 publications

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“…Distal chromosome 2q is an important candidate region for IDDM susceptibility not only because several susceptibility genes have been mapped to this region in Caucasian populations [14,21,25,26], but also because this region is syntenic to murine chromosome 1, where a susceptibility gene for IDDM was mapped in the NOD mouse [22,23]. Recently, Morahan et al [21] mapped a susceptibility gene for IDDM (IDDM13) to the D2S137±D2S164 interval on chromosome 2q.…”

Section: Discussionmentioning

confidence: 99%

“…This region is an important candidate region for IDDM susceptibility not only because susceptibility genes have been mapped to this region in Caucasian populations, but also because this region is syntenic to murine chromosome 1 where a susceptibility gene for IDDM (Idd5) was mapped in the nonobese diabetic (NOD) mouse [22,23]. To study the contribution of this region to IDDM susceptibility further and to narrow the region for subsequent positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population.…”

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Association of distal chromosome 2q with IDDM in Japanese subjects

Ikegami

Kawaguchi

et al. 1998

Diabetologia

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Insulin-dependent diabetes mellitus (IDDM) is caused by autoimmune destruction of insulin-producing beta cells of the pancreas in genetically susceptible individuals [1]. Inheritance of IDDM is polygenic with a major locus (IDDM1) in the major histocompatibility complex (MHC) [2,3]. Several additional loci have recently been mapped to the human genome by whole genome scanning with random markers [4±8] and/or a candidate gene approach [9±14]. Most reports, however, are based on data in Caucasian populations, and it is yet to be determined whether loci mapped in one population universally contribute to IDDM susceptibility in other populations.The Japanese population is unique in studies on the genetics of IDDM not only because they are genetically distinct from Caucasian populations, but also because the incidence of IDDM is very low in this population [15]. We have previously reported that two IDDM loci, IDDM1 in HLA region [15,16] and IDDM2 in the insulin gene (INS) region [17], both of which were identified by the candidate gene approach, contribute to IDDM susceptibility in Japanese in the same way as in Caucasians. The contribution of other loci, however, to IDDM susceptibility in Japanese is largely unknown due to their low incidence and, as a consequence, the limited number of multiplex families with IDDM. Diabetologia (1998) Summary An insulin-dependent diabetes mellitus (IDDM)-susceptibility gene (IDDM13) has recently been mapped to a region of distal chromosome 2q, which is syntenic to the region of mouse chromosome 1 containing a murine susceptibility gene for IDDM, Idd5. To determine the contribution of this region to IDDM disease susceptibility further and to narrow the region for positional cloning of susceptibility genes, we have studied the association of distal chromosome 2q with IDDM in the genetically distinct Japanese population. A 137 mobility unit (mu) allele at D2S137 locus was significantly associated with IDDM (odds ratio 1.92, p = 0.0016). Other markers, D2S301 and D2S143, located in the same region were not associated with IDDM, indicating that IDDM13 is in linkage disequilibrium with D2S137, but not with D2S301 or D2S143. The association of D2S137 with IDDM was observed in patients lacking one of two high risk HLA alleles, DQB1*0303 and DQB1*0401, but not in patients with either of these alleles. The frequency of high risk HLA alleles was significantly lower in patients with the susceptible allele at D2S137, suggesting that IDDM13 contributes to IDDM susceptibility in subjects without high risk genotypes at IDDM1. Demonstration of allelic association of D2S137 with IDDM localizes IDDM13 in the close vicinity (< 2 centiMorgans) of D2S137, greatly facilitating fine structure mapping and positional cloning of IDDM13. [Diabetologia (1998) 41: 228±232]

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Association of distal chromosome 2q with IDDM in Japanese subjects

Ikegami

Kawaguchi

et al. 1998

Diabetologia

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“…[139][140][141] It is important in this regard that a single peak near the D2S1391 marker, with a LOD score of 2.62, was reported in the study by Cox et al 21 Part of this region is homologous to the region of mouse chromosome 1 containing the murine T1D susceptibility locus, idd5, in the non-obese diabetic (NOD) mouse. 142,143 A number of genes have been proposed and investigated as candidate genes for the IDDM7 region. These include genes of the interleukin-1 gene cluster (ie IL1R1, [144][145][146] IL1B, 130,147,148 and IL1RN 130,149 ) HOXD8, 150 GAD1, 151 GALNT3, 141 and NEUROD.…”

Section: Iddm2-the Insulin Gene (Ins) Regionmentioning

confidence: 99%

Genetics of type 1 diabetes mellitus

2002

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“…This region is homologous to that on proximal mouse chromosome 1 where the Idd5 T1D gene was subsequently identified in diabetesprone NOD mice [66], and contains the disease candidate genes CTLA4 and CD28 that encode receptors on T cells involved in control of T cell activation. CTLA4 (at 2q33) was considered a strong candidate because it mediates T cell apoptosis and negatively regulates T cell activation [67].…”

Section: Ctla4mentioning

confidence: 99%

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

Baxter

Jordan²

2012

Rev Diabet Stud

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■ AbstractBy the year 2000, a draft of the human genome sequence was completed. Millions of single-nucleotide polymorphisms (SNPs) had been deposited into public databases, and high throughput technologies were under development for SNP genotyping. At that time, it was predicted that large case control association studies would provide far better resolution and power than genome-wide linkage studies. Type 1 diabetes was one of the first phenotypes to be examined by genome-wide association studies (GWAS), and to date over 50 genomic regions have been associated with the disease.In general, the great majority of these loci individually contribute a relatively small degree of risk, and most loci lie outside of coding sequences. The identification of molecular mechanisms from these genomic data therefore remains a significant challenge. Here, we summarize genetic candidate, linkage, and association studies of type 1 diabetes and discuss a potential strategy to identify mechanisms of disease from genomic data.

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Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/lty/Bcg genes on chromosome 1

Cited by 164 publications

References 24 publications

Association of distal chromosome 2q with IDDM in Japanese subjects

Association of distal chromosome 2q with IDDM in Japanese subjects

Genetics of type 1 diabetes mellitus

From Markers to Molecular Mechanisms: Type 1 Diabetes in the Post-GWAS Era

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