GENES FOR INSULIN DEPENDENT DIABETES MELLITUS

胰岛素依赖性糖尿病的基因

• 批准号: 6517265
• 负责人: Richard S SPIELMAN
• 金额: $ 55.74万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6517265
• 关键词: artificial chromosomes; chromosome 21; diabetes mellitus genetics; family genetics; gene environment interaction; gene expression; genetic markers; genetic polymorphism; genetic susceptibility; genome; genotype; human genetic material tag; insulin dependent diabetes mellitus; linkage disequilibriums; linkage mapping; molecular cloning; nucleic acid hybridization; nucleic acid probes; polymerase chain reaction; statistics /biometry

Insulin-dependent diabetes mellitus (IDDM) is a serious chronic disease which results from autoimmune destruction of the pancreatic islet cells. The events that initiate this pathogenic process are poorly understood. The tendency of IDDM to cluster in families and the low (35-40 percent) concordance in identical twins suggest that both genetic and environmental factors contribute to IDDM susceptibility. Although intense attention has been centered on genetic susceptibility associated with the HLA system on chromosome 6p, other genes also contribute. We and others have searched for regions of the human genome that demonstrate genetic linkage to IDDM. Beside HLA, we have identified 1 additional region where there is significant evidence of linkage and 4 other regions with suggestive evidence. In this current application, we propose to extend these promising results by accomplishing the following aims. 1. Merge our consortium genotype data with those from the groups of John Todd and Mark Lathrop and carry our analyses of the combined material. 2. Expand our genome scan beyond its present state, by typing additional genetic markers (simple tandem repeat polymorphism, STRPs). 3. Genotype additional markers in five candidate regions where linkage with IDDM is suggestive, to maximize the evidence for linkage and to search for linkage disequilibrium. 4. Identify susceptibility genes for IDDM in candidate regions we have defined, using genomic mismatch scanning (GMS), as well as more standard techniques of positional cloning. 5. Apply the technology of GMS to test for shared genetic ancestry (identity by descent) at the loci for 100-200 immunologically defined candidate genes, regardless of map location (see linked grant by Concannon). Identification of genes for IDDM susceptibility should provide important insights into immune pathways that are disrupted in IDDM and may suggest novel preventative or therapeutic approaches.

胰岛素依赖性糖尿病（IDDM）是一种严重的慢性疾病

项目成果

The TDT and other family-based tests for linkage disequilibrium and association.

• 发表时间: 1996-11
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: R. Spielman;W. Ewens

The transmission/disequilibrium test: history, subdivision, and admixture.

• 发表时间: 1995-08
• 期刊: American journal of human genetics
• 影响因子: 9.8
• 作者: W. Ewens;R. Spielman

Linkage and association with type 1 diabetes on chromosome 1q42.

• DOI: 10.2337/diabetes.51.11.3318
• 发表时间: 2002-11
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: K. Ewens;L. Johnson;B. Wapelhorst;K. O'Brien;S. Gutin;V. A. Morrison;C. Street;S. Gregory;R. Spielman;P. Concannon

Linkage and association studies in insulin-dependent diabetes with a new dinucleotide repeat polymorphism at the GAD65 locus.

• DOI: 10.3109/08916939508993360
• 发表时间: 1995
• 期刊: Autoimmunity
• 影响因子: 3.5
• 作者: B. Wapelhorst;G. Bell;N. Risch;R. Spielman;P. Concannon

Linkage-disequilibrium mapping without genotyping.

无需基因分型的连锁不平衡图谱。

• DOI: 10.1038/ng0398-225
• 发表时间: 1998
• 期刊: Nature genetics.
• 作者: Cheung,VG;Gregg,JP;Gogolin-Ewens,KJ;Bandong,J;Stanley,CA;Baker,L;Higgins,MJ;Nowak,NJ;Shows,TB;Ewens,WJ;Nelson,SF;Spielman,RS
• 通讯作者: Spielman,RS