Fine mapping and Positional Cloning of Diabetes Genes

糖尿病基因的精细定位和定位克隆

基本信息

批准号：
7642528
负责人：
Yuanxiu Chen
金额：
$ 28.48万
依托单位：
HOWARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-01 至 2011-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7642528
关键词：
19p Abdomen Adult Affect Africa African African American Albumins Alleles Americas Asians Biochemical Bioinformatics Blood Pressure Body Composition Body fat C-Peptide C-reactive protein Calcium Calories Candidate Disease Gene Cardiovascular system Cause of Death Cells Cheek structure Cholesterol Chromosomes Chromosomes, Human, Pair 12 Chromosomes, Human, Pair 19 Chromosomes, Human, Pair 5 Classification Clinical Cohort Studies Collaborations Communities Creatinine Custom DNA Data Data Set Databases Diabetes Mellitus Diet Endocrinologist Endothelin-1 Enrollment Environment Environmental Risk Factor Epidemiologic Studies Epidemiologist Epidemiology Ethnic Origin Etiology European Eye Family Family history of Fatty acid glycerol esters Finland Follow-Up Studies Funding Generations Genes Genetic Genome Scan Genomics Genotype Geographic Locations Ghana Glaucoma Glucose Haplotypes Height High Density Lipoprotein Cholesterol Hip region structure Human Incidence Individual Institutes Insulin Insulin Receptor Intercistronic Region Interleukin-6 International Investigation Kenya LDL Cholesterol Lipoproteins Laboratories Leptin Limb structure Link Lipids Mails Maps Measurement Measures Microsatellite Repeats Molecular National Human Genome Research Institute Neurologic Nigeria Non-Insulin-Dependent Diabetes Mellitus Nurses Obesity Participant Patients Pattern Peptides Persons Phase Phenotype Physical Examination Physical activity Physiologic Intraocular Pressure Population Population Genetics Positioning Attribute Predisposition Primary Care Physician Primary Open Angle Glaucoma Questionnaires Reading Recording of previous events Recurrence Request for Applications Research Research Personnel Resolution Risk Risk Factors SNP genotyping Sampling Serum Siblings Site Sorting - Cell Movement Susceptibility Gene Thinking Triglycerides United States Urea Uric Acid Variant Weight Woman Women&apos s Health Work base case control chromosome 5q loss cohort density electric impedance exhaust falls follow-up genetic linkage analysis genetic pedigree genetic variant genome-wide linkage health disparity leptin receptor minority health mortality nexin novel positional cloning programs resistin trait

项目摘要

DESCRIPTION (provided by applicant): The Africa America Diabetes Mellitus (AADM) Study represents one of the primary attempts to identify T2DM susceptibility genes in West African ancestral populations of African-Americans. Through an international collaboration between African and US investigators, affected sib-pairs (ASP) from Nigeria and Ghana were characterized for demographic, clinical, and biochemical measurements. Microsatellite genotyping for a genome scan was conducted by CIDR. Linkage was observed for T2DM on chromosomes 12, 19 and 20, for insulin on chromosome 19 and for intraocular pressure (IOP, indicative of glaucoma, one of the eye complications of T2DM) on chromosome 5. Fine mapping, at ~ 2 cM marker density, of the linkage regions forT2DM, insulin, glucose, and IOP was performed. We observed the following notable results: 1) T2DM: chromosome 5 - LOD=3.13, 1 unit LOD support interval 117-135 cM; 2) IOP: chromosome 5 - LOD=4.68, support interval 105-158 cM); and 3) insulin: chromosome 19 - LOD=2.57, support interval 12 - 33 cM. The T2DM and the IOP linkage regions on chromosome 5 overlap. The 19p region contains both the insulin receptor and resistin genes. The 5q region contains the Sorting Nexin 2 gene which interacts with insulin and leptin receptors, as well as a new adult-onset primary open-angle glaucoma locus on 5q22.1 designated GLCIG. Following reviewers' advice, we submitted an application to CIDR to conduct SNP typing on chromosome 5 and 19. A total of 4,608 SNPs in 460 sibships (n=1380 persons) at a density of 5-6 kb within genes and 11-12 kb for intergenic regions was requested. Linkage and family-based association analyses will be conducted. Identified candidate genes/loci will be re-sequenced and functional SNPs will be typed in 1000 cases and 1000 controls to perform ethnically matched association and LD mapping studies. Phenotype/genotype association will be assessed and functional associations will be repeated in four groups - Yoruba, Nigeria; Luyha, Kenya; African Americans and Finns in the FUSION study

描述（由申请人提供）：非洲美国糖尿病（AADM）研究是鉴定非裔美国人西非祖先种群T2DM易感基因的主要尝试之一。通过非洲和美国调查人员之间的国际合作，来自尼日利亚和加纳的受影响的SIB对（ASP）的特征是人口，临床和生化测量值。 CIDR进行了基因组扫描的微卫星基因分型。 Linkage was observed for T2DM on chromosomes 12, 19 and 20, for insulin on chromosome 19 and for intraocular pressure (IOP, indicative of glaucoma, one of the eye complications of T2DM) on chromosome 5. Fine mapping, at ~ 2 cM marker density, of the linkage regions forT2DM, insulin, glucose, and IOP was performed.我们观察到以下值得注意的结果：1）T2DM：5 -LOD染色体= 3.13，1个单位LOD支撑间隔117-135 cm； 2）IOP：5染色体-LOD = 4.68，支撑间隔105-158 cm）;和3）胰岛素：19染色体19- LOD = 2.57，支撑间隔12-33厘米。 5号染色体上的T2DM和IOP链接区域重叠。 19p区域既包含胰岛素受体和抵抗蛋白基因。 5Q区域包含与胰岛素和瘦素受体相互作用的分类Nexin 2基因，以及在5Q22.1指定的Glcig上的新成人发作的原发性开态青光眼基因座。遵循审阅者的建议，我们向CIDR提交了在5和19染色体上进行SNP的申请。在基因内的460个sibships（n = 1380人）中，基因的密度为460个SIBShips（n = 1380人），间基因区域为11-12 kb。将进行链接和基于家庭的关联分析。确定的候选基因/基因座将重新列出，功能性SNP将在1000例和1000个对照中键入以进行种族匹配的关联和LD映射研究。将评估表型/基因型关联，并将在四组中重复功能关联 - 尼日利亚约鲁巴；肯尼亚卢伊哈；融合研究中的非裔美国人和芬兰人