Identification of the IBD genes on chromosomes 3p and 6p

染色体 3p 和 6p 上 IBD 基因的鉴定

• 批准号: 7469915
• 负责人: John D. Rioux
• 金额: $ 60.32万
• 依托单位: MONTREAL HEART INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7469915
• 关键词: Adolescent; Affect; Age; Alleles; American; Antioxidants; Bioinformatics; Biological; Biological Assay; Biology; Biopsy; Candidate Disease Gene; Cell Line; Cells; Chromosomes; Chromosomes, Human, Pair 3; Classification; Clinical; Colitis; Collaborations; Colon; Complex; Complex Genetic Trait; Condition; Crohn' s disease; Data; Data Set; Depth; Development; Disease; Disease Association; Disease susceptibility; Environment; Epithelial; European; Evaluation; Funding; Future; Gap Junctions; Gastrointestinal tract structure; Gene Expression; Genes; Genetic; Genetic Epistasis; Genetic Models; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Research; Genetic Risk; Genetic Transcription; Genetic Variation; Genome; Genomics; Genotype; Genus Cola; Goals; Grant; HLA-B Antigens; Haplotypes; Health; Human; Individual; Inflammatory; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Institution; Intercistronic Region; Intestines; Knowledge; Link; Logistics; Lymphocyte; Major Histocompatibility Complex; Maps; Modeling; Mus; NOTCH4 gene; National Institute of Diabetes and Digestive and Kidney Diseases; Nexus (resin cement); Numbers; Pathway Analysis; Pathway interactions; Patients; Phenotype; Population; Process; RHOA gene; RNA; RNA Interference; Regression Analysis; Reporter; Reporting; Research; Research Personnel; Resources; Response Elements; Risk; Risk Factors; Role; Sampling; Screening procedure; Secondary to; Signal Pathway; Signal Transduction; Structure; Surveys; Susceptibility Gene; T-Lymphocyte; Technology; Time; Transcription Factor AP-1; Ulcerative Colitis; Upper arm; Validation; Variant; Work; case control; cell mediated immune response; cohort; density; design; disorder control; disorder risk; experience; expression cloning; functional genomics; genetic risk factor; genetic variant; genome wide association study; insertion/deletion mutation; mutant; novel; protein expression; research study; response; size; young adult

DESCRIPTION (provided by applicant): Crohn's disease (CD) and ulcerative colitis (UC) are two common inflammatory diseases of the gastrointestinal tract, collectively known as the inflammatory bowel diseases (IBD). It is estimated that as many as one million Americans are affected with these debilitating diseases. IBD may occur in people of all ages, but it is primarily a disease that arises in adolescents and young adults. Currently there is no known cure for IBD. Over the last five years, a number of IBD genes (CARD15, IBD5, MYO9B, IL23R, ATG16L1) have been identified, but these do not explain all of the genetic risk to IBD. We have previously reported evidence of linkage to two regions of the genome (located on the short arms of chromosomes 3 and 6) - indicating the presence of additional IBD genes. In the last four years we performed candidate and positional association mapping studies of these two chromosomal regions that have led to the identification of significantly associated alleles or putative genetic risk factors in the targeted regions. In this application, we propose to identify all of the casual alleles in the genes that we have identified and also to identify secondary risk factors for which we have found significant evidence. In the last few years it has also become clear that one of the major challenges in the study of complex genetic traits is to determine how disease genes and their corresponding alleles exert their influence on the biology of health and disease. We therefore aim to employ a limited set of functional approaches that will be commonly applied to a set of IBD risk genes. This systematic pathway analysis will help guide future in-depth functional studies and will provide the beginnings of a common framework by which we can build a model of how these genetic variants influence biological pathways eventually leading to the development of IBD.

描述（申请人提供）：克罗恩病（CD）和溃疡性结肠炎（UC）是两种常见的胃肠道炎症性疾病，统称为炎症性肠病（IBD）。据估计，有多达一百万美国人患有这些使人衰弱的疾病。 IBD 可能发生在所有年龄段的人中，但它主要是一种发生于青少年和年轻人的疾病。目前还没有已知的 IBD 治疗方法。在过去五年中，已鉴定出许多 IBD 基因（CARD15、IBD5、MYO9B、IL23R、ATG16L1），但这些并不能解释 IBD 的所有遗传风险。我们之前报道过与基因组的两个区域（位于 3 号和 6 号染色体的短臂上）连锁的证据 - 表明存在额外的 IBD 基因。在过去的四年中，我们对这两个染色体区域进行了候选和位置关联图谱研究，从而鉴定了目标区域中显着相关的等位基因或推定的遗传风险因素。在此应用中，我们建议鉴定我们已鉴定的基因中的所有偶然等位基因，并鉴定我们已找到重要证据的次要风险因素。在过去几年中，人们也清楚地认识到，复杂遗传性状研究的主要挑战之一是确定疾病基因及其相应的等位基因如何对健康和疾病的生物学产生影响。因此，我们的目标是采用一组有限的功能方法，这些方法通常适用于一组 IBD 风险基因。这种系统的途径分析将有助于指导未来深入的功能研究，并将提供一个共同框架的起点，通过该框架我们可以建立一个模型，了解这些遗传变异如何影响生物途径，最终导致 IBD 的发展。