Modifier genes in CF-related diabetes and meconium ileus

CF 相关糖尿病和胎粪性肠梗阻的修饰基因

• 批准号: 7314125
• 负责人: SCOTT M BLACKMAN
• 金额: $ 5.89万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7314125
• 关键词: Affect; Biological; Candidate Disease Gene; Chloride Channels; Chromosomes, Human, Pair 3; Chromosomes, Human, Pair 4; Clinical; Code; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA; Data; Defect; Diabetes Mellitus; Disease; Epithelial; Family; Fellowship; Functional disorder; Genes; Genetic; Genome; Genotype; Goals; Haplotypes; Ileus; Individual; Intestinal Obstruction; Ions; Link; Liquid substance; Maps; Meconium; Names; Neonatal; Numbers; Other Genetics; Patients; Phenotype; Risk; Short Tandem Repeat Polymorphism; Siblings; Single Nucleotide Polymorphism; Testing; Tissues; Twin Multiple Birth; Twin Studies; base; cystic fibrosis patients; density; disorder risk; experience; genetic association; genetic linkage analysis; genome wide association study; transmission process

DESCRIPTION (provided by applicant): Cystic fibrosis is a fatal disease caused by defects in CFTR, a chloride channel that is essential for ion and fluid transport in epithelial tissues. Variability in CF disease course and complications, even in patients with identical CFTR genotypes, indicates that other genetic, environmental, or stochastic (random) factors also contribute. Twin studies have revealed that genetic factors other than CFTR underlie much of the risk for two significant complications of CF: meconium ileus, a severe neonatal intestinal obstruction, and CF-related diabetes, which is correlated with increased CF complications and reduced survival. A genome-wide scan has led to identification of genetic loci likely to be linked to these phenotypes. In this project a candidate gene approach will be used to identify genes within these linkage peaks which modify the risk for CF-related diabetes and meconium ileus. Candidates will be selected based on biological plausibility, using our group's extensive experience in CF pathophysiology. An optimal set of single nucleotide polymorphisms will be identified, and DNA from CF patient families will be genotyped. Genetic association and additional linkage analysis will confirm or exclude each candidate gene, as well as refine the linkage peaks.

描述（由申请人提供）：囊性纤维化是由CFTR缺陷引起的致命疾病，CFTR是一种氯化物通道，对于上皮组织中的离子和液体转运至关重要。 CF疾病病程和并发症的可变性，即使在具有相同CFTR基因型的患者中，也表明其他遗传，环境或随机（随机）因素也会促进。双胞胎研究表明，CFTR以外的其他遗传因素是CF两种重要并发症的许多风险：回肠循环，严重的新生儿肠梗阻和与CF相关的糖尿病，这与CF并发症增加和生存率降低相关。全基因组扫描已导致对可能与这些表型相关的遗传基因座的鉴定。在该项目中，将使用候选基因方法来识别这些连锁峰内的基因，从而改变了CF相关糖尿病和小幼虫的风险。将根据我们小组在CF病理生理学方面的丰富经验，根据生物学合理性选择候选人。将确定一组最佳的单核苷酸多态性，并将对CF患者家族的DNA进行基因分型。遗传关联和其他连锁分析将确认或排除每个候选基因，并完善连锁峰。