MA Admixture Mapping Development & Application to NIDDM

MA 外加剂测绘开发

• 批准号: 7416787
• 负责人: Michael F. Seldin
• 金额: $ 42.66万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7416787
• 关键词: Admixture; African; African American; Algorithms; American; Asians; California; Case Study; Chinese American; Chinese People; Chromosomes; Cities; Communities; Complement; Complex; Control Groups; DNA; Data; Derivation procedure; Development; Diabetes Mellitus; Diabetic Nephropathy; Disease; European; Gene Frequency; Generations; Genes; Genome; Genotype; Hereditary Disease; Kidney Diseases; Location; Maps; Methods; Mexican; Mexican Americans; Mexico; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Phase; Population; Predisposition; Principal Investigator; Resources; Sampling; Science; Signal Transduction; Single Nucleotide Polymorphism; Structure; Study models; Susceptibility Gene; Testing; Texas; Validation; base; case control; density; design; diabetic; genetic linkage analysis; markov model; non-diabetic; programs; simulation; tool

DESCRIPTION (provided by applicant): Recently, substantial progress has been made in development and application of admixture mapping including derivation of appropriate statistical tools and testing in African American populations. The implementation of this approach in Mexican Americans (MA) has been hampered by the lack of a sufficient density of markers that can provide the ancestry information distinguishing the two major parental populations, Amerindians (Al) and European that contribute to this admixed population. The current proposal will remedy this problem by identification, validation and analysis of a panel of >5000 AI/European American (EA) Ancestry Informative Markers (AIMs) distributed over the genome. The panel of AIMs will be tested using a large collected set of MA DNA samples from type 2 diabetics with nephropathy (750 samples) or without nephropathy (600 samples) and a smaller matched set of nondiabetic MA subjects (300 samples). The utilization of this set will enable both case only and case control designs to be examined using a variety of recently developed algorithms. The first phase of the study (identification of AI/EA AIMs) will utilize an enrichment strategy based on pre-selecting AIMs dependent on putative Chinese/EA AIMs that have been identified in a completed 1.6 x 106 SNP screen. Over 23,000 putative Chinese/EA AIMs with Fsts > 0.45 have been identified and these will be used to examine 48 Pima Amerindian samples. Our previous studies conservatively suggest that >25% of these putative Chinese/EA AIMs will have an AI/EA Fst > 0.4. In the second phase > 5000 AI/EA AIMs will be chosen based on both Fst and chromosomal location to achieve a high density AIMs panel. This will be validated utilizing an additional set of 48 Pima Amerindians in addition to testing two other Al groups (96 samples each) and EA (96 samples). The MA populations will be examined using this panel that is expected to include >4000 validated EA/AI AIMs and analyzed to 1) define chromosomal segments derived from EA and Al, 2) perform modeling studies and 3) identify putative diabetes and diabetic nephropathy associated regions distinguishing the major ancestry. Finally, the three strongest signals will be further investigated utilizing a dense set of SNPs in the putative susceptibility regions.

描述（由申请人提供）：最近，在混合映射的开发和应用中取得了很大进展，包括推导适当的统计工具和非裔美国人人口测试。由于缺乏足够密度的标志物，可以为祖先提供的祖先信息（Al Amerindians（AL）和欧洲）的祖先信息提供足够密度，从而妨碍了这种方法在墨西哥裔美国人（MA）的实施，从而阻碍了这种方法。当前的提案将通过对> 5000 AI/欧美（EA）祖先信息标记（AIMS）的小组的识别，验证和分析来解决此问题。目标面板将使用来自肾病（750个样本）的2型糖尿病患者或没有肾病（600个样本）和一组较小匹配的Nondiabetic MA受试者（300个样品）的大量收集的MA DNA样品进行测试。该集合的利用率将仅使案例和案例控制设计可以使用各种最近开发的算法进行检查。该研究的第一阶段（AI/EA目标的识别）将基于基于预选的目的采用富集策略，取决于已在完成的1.6 x 106 SNP屏幕中已确定的中文/EA目标。已经确定了超过23,000个具有FSTS> 0.45的中文/EA目标，这些目标将用于检查48个PIMA Amerindian样本。我们以前的研究保守地表明，这些推定的中文/EA目标中的25％将具有AI/EA FST> 0.4。在第二阶段> 5000 AI/EA/EA的目标将根据FST和染色体位置选择，以实现高密度的目标面板。除了测试另外两个Al组（每个96个样本）和EA（96个样本）外，还将使用另外48个Amerindians（96个样本）进行验证。将使用此面板对MA种群进行检查，该面板预计将包括> 4000个经过验证的EA/AI目标，并分析至1）定义源自EA和AL的染色体片段，2）进行建模研究和3）确定假定的糖尿病和糖尿病肾病相关区域，以区分主要的血统。最后，将使用推定的易感性区域中的一组密集的SNP进一步研究三个最强的信号。