Approaches to Gene Mapping Development and Applications

基因图谱开发和应用的方法

• 批准号: 7289909
• 负责人: STEPHEN J O'BRIEN
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7289909
• 关键词: Approaches; Gene; Mapping; Development; Applications

Mapping by admixture linkage disequilibrium (MALD) is a theoretically powerful, although unproven, approach to mapping genetic variants that are involved in human disease. MALD takes advantage of long-range haplotypes that are generated by gene flow among recently admixed ethnic groups, such as African-Americans and Latinos. Under ideal circumstances, MALD will have more power to detect some genetic variants than other types of genome-wide association study that are carried out among more ethnically homogeneous populations. It will also require 200-500 times fewer markers, providing a significant economic advantage. The MALD approach is now being applied, with results expected in the near future. We determined allele frequencies for 1,913 short tandem repeat (STR) markers in European-derived populations as well as in African Americans. These allele frequencies allowed us to compute several measures of ethnic population frequency differences including composite delta, Fisher information content, and Shannon information content. Two hundred seventy-eight (14.4%) of the STR markers were found to have a Shannon information content value between Europeans and Africans of greater than or equal to 0.2. Only the top 42% of the highly selected single nucleotide polymorphism (SNP) MALD map markers equal or exceed this amount. This demonstrates that accurate assessment of allele frequencies for STR markers in genetically distinct ethnic populations represents an efficient method for the identification of MALD markers. Markers selected from the new set of 1,913 STR markers are being merged with the 744 previously reported STR markers to provide an STR-based MALD map that can enhance the SNP-based MALD map.

通过混合连锁不平衡（MALD）作图是一种理论上强大的，尽管未经证实的，绘制与人类疾病有关的遗传变异的方法。MALD利用了远程单倍型，这些单倍型是由最近混合的种族群体（如非洲裔美国人和拉丁美洲人）之间的基因流动产生的。在理想的情况下，MALD将比其他类型的全基因组关联研究更有能力检测一些遗传变异，这些研究是在更种族同质的人群中进行的。它所需的标记物也将减少200-500倍，具有显著的经济优势。目前正在应用MALD方法，预期在不久的将来会有结果。我们测定了1913个短串联重复（STR）标记在欧洲人和非裔美国人中的等位基因频率。这些等位基因频率使我们能够计算几种不同种族人口频率差异的测量方法，包括复合δ、Fisher信息含量和Shannon信息含量。发现278个（14.4%）STR标记在欧洲人和非洲人之间的香农信息含量值大于或等于0.2。只有前42%的高度选择的单核苷酸多态性（SNP） MALD地图标记等于或超过这个数量。这表明，在遗传上不同的民族群体中准确评估STR标记的等位基因频率是鉴定MALD标记的有效方法。从新的1,913个STR标记中选择的标记正在与先前报道的744个STR标记合并，以提供基于STR的MALD图，可以增强基于snp的MALD图。