DETECTION OF LINKAGE DISEQUILIBRIUM IN AFRICAN AMERICANS NEAR THE FY GENE

非洲裔美国人 FY 基因附近连锁不平衡的检测

• 批准号: 6161151
• 负责人: J A LAUTENBERGER
• 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/6161151
• 关键词: African American; artificial chromosomes; genetic disorder; genetic markers; human genetic material tag; human population genetics; human tissue; linkage disequilibriums; point mutation; restriction fragment length polymorphism

Linkage disequilibrium can be produced by the admixture of previously separated populations containing polymorphic loci with different allele frequencies between the groups. This is the basis of the method for mapping disease loci called mapping by admixture linkage disequilibrium (MALD). African Americans (AAs) are a suitable population for MALD studies since they have an estimated 15% - 30% Caucasian ancestry. To obtain parameters that will be useful for the design of future MALD studies, an investigation was initiated to determine the extent of linkage disequilibrium in AAs in the vicinity of the FY locus. In essence, most AAs and all Africans have a point mutation in the FY promoter that is absent in Caucasians. A high-throughput converted restriction fragment length polymorphism assay was developed for this mutation and performed on a panel of DNAs from 2,268 individuals. Of the 790 AAs included in this analysis, 31 were found to be homozygous for the Caucasian allele, 248 were heterozygous, and the remainder were homozygous for the African allele. The map location of FY relative to chromosome 1 markers D1S2635 and SPTA1 was confirmed by analysis of yeast artificial chromosomes (YACs) and radiation hybrid mapping. Two separate YACs contain all three of these markers, indicating that they reside within a 1.7 megabase segment of DNA. In addition, a panel containing 22 fluorescent dye-labeled microsatellite markers was devised to detect potential linkage disequilibrium at distances up to 30 centiMorgans on each side of FY. The marker density is greatest in the immediate vicinity of that gene. These markers were shown to amplify products of the expected size in a panel of DNAs established to optimize polymerase chain reaction conditions. These markers will be typed on DNAs from the 31 AAs homozygous for the Caucasian FY allele as well as about 70 samples each from heterozygous AAs and AAs homozygous for the African allele. Statistical tests will be performed to determine if the allele distribution for the flanking markers is significantly different among these three groups. These results will help elucidate the distance that MALD will be effective in establishing linkage between disease loci and microsatellite markers in genome-wide surveys.

连锁不平衡可以由先前的 含有不同等位基因多态位点的分离群体 组之间的频率。这是该方法的基础， 混合连锁不平衡作图法 （MALD）。非裔美国人（AAs）是MALD的合适人群 因为他们估计有15% - 30%的白人血统。到 获得对未来MALD设计有用的参数 研究，开始进行调查，以确定 FY位点附近的AA连锁不平衡。在 本质上，大多数AA和所有非洲人在FY中有点突变 在高加索人中不存在的启动子。高通量转换 限制性片段长度多态性分析开发了这个 突变并在来自2，268个个体的DNA组上进行。的 790例AA被纳入该分析，31例被发现是纯合子， 高加索人等位基因，248个是杂合子，其余的是 非洲等位基因的纯合子 FY相对于1号染色体标记D1 S2635和D1 S2635的图谱定位 通过酵母人工染色体（YACs）分析证实了SPTA 1。 和辐射混合测绘。两个独立的YAC包含所有三个 这些标记，表明它们位于1.7兆字节段内， 的DNA。此外，一组含有22个荧光染料标记的 设计了微卫星标记来检测潜在的连锁 在FY的每一侧距离达30厘米摩根的不平衡。 标记密度在该基因的紧邻处最大。 这些标记物显示出在一个扩增子中扩增预期大小的产物。 建立一组DNA以优化聚合酶链反应 条件这些标记将在来自31个AA的DNA上进行分型 高加索人FY等位基因纯合子以及各约70个样本 来自杂合子AA和非洲等位基因纯合子AA。 将进行统计学检验，以确定等位基因 侧翼标记的分布在以下群体中显著不同： 这三个群体。这些结果将有助于阐明 MALD将有效地建立疾病位点之间的连锁， 微卫星标记在全基因组调查中的应用