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：
7235406
负责人：
Yuanxiu Chen
金额：
$ 43.39万
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 2010-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7235406
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 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 Human Genome 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 N-(deoxyguanosin-8-yl)-2-aminopyrene 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 Purpose Questionnaires Rate Reading Recording of previous events Recurrence Request for Applications Research Research Institute 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）：非洲美洲糖尿病 (AADM) 研究是确定西非非裔美国人祖先人群中 T2DM 易感基因的主要尝试之一。通过非洲和美国研究人员之间的国际合作，对来自尼日利亚和加纳的受影响同胞对 (ASP) 进行了人口统计、临床和生化测量的特征分析。 CIDR 进行了基因组扫描的微卫星基因分型。在 12、19 和 20 号染色体上观察到 T2DM 的连锁，在 19 号染色体上观察到胰岛素的连锁，在 5 号染色体上观察到眼内压（IOP，表明青光眼，T2DM 的眼部并发症之一）的连锁。精细绘图，标记密度约为 2 cM进行了 T2DM、胰岛素、葡萄糖和 IOP 的连锁区域的分析。我们观察到以下显着结果： 1) T2DM：5 号染色体 - LOD=3.13，1 单位 LOD 支持区间 117-135 cM； 2) IOP：5号染色体-LOD=4.68，支持区间105-158 cM)； 3) 胰岛素：19 号染色体 - LOD=2.57，支持区间 12 - 33 cM。 T2DM 和 IOP 连锁区域在 5 号染色体上重叠。 19p 区域包含胰岛素受体和抵抗素基因。 5q 区域包含与胰岛素和瘦素受体相互作用的分选 Nexin 2 基因，以及 5q22.1 上一个新的成人发病的原发性开角型青光眼基因座，称为 GLCIG。根据审稿人的建议，我们向 CIDR 提交了一份申请，对 5 号和 19 号染色体进行 SNP 分型。460 个同胞（n=1380 人）总共有 4,608 个 SNP，基因内密度为 5-6 kb，基因内密度为 11-12 kb要求提供基因间区域。将进行关联分析和基于家族的关联分析。已确定的候选基因/位点将被重新测序，并且将在 1000 个病例和 1000 个对照中对功能性 SNP 进行分型，以进行种族匹配的关联和 LD 作图研究。将评估表型/基因型关联，并在四组中重复功能关联——约鲁巴、尼日利亚；肯尼亚卢伊哈； FUSION 研究中的非裔美国人和芬兰人