NEW VARIABLE POLYMORPHISMS

新的变量多态性

• 批准号: 6301739
• 负责人: LUIGI L CAVALLI-SFORZA
• 金额: $ 28.24万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6301739
• 关键词: biochemical evolution; computer assisted sequence analysis; computer program /software; gene expression; gene frequency; gene mutation; genetic markers; genetic polymorphism; genotype; high performance liquid chromatography; human genetic material tag; human migration; human population genetics; human tissue; mitochondrial DNA; natural selections; nucleic acid repetitive sequence; sequence tagged sites; sex chromosomes; statistics /biometry

This subproject will be devoted to genotyping a large number of new polymorphisms in part found by us, and in part found by external initiatives. We plan to genotype DNAs supplied by the world wide collection of cell lines being developed at CEPH in collaboration with us, with the aim of understanding the history of human evolution and the role of the classical evolutionary factors (mutation, natural selection, drift and migration) in determining human genetic variation. The genotyping method will be that developed in the course of this Program Project for finding and testing new genetic polymorphisms, DHPLC (Denaturing High Performance Liquid Chromatography). It will be perfected or replaced by other methods should a new one prove more valuable in terms of cost, given equal accuracy. In particular, we will analyze the variation of the whole mitochondrial DNA (excluding the D-loop, which has already been widely explored). At the time the new Program Project begins, we expect to have generated about 450 mostly new mtDNA SNPs. We also want to type, in the same way, a large number of Y chromosome mutants, which we plan to continue to provide, with the support of another grant, NIH GM55273, from an increasing variety of Y chromosome locations on the chromosome. A selected number of known X chromosome genes will be similarly studied in males. We have shown that Y mutants have a variation between populations almost three times larger than mtDNA mutants. We have given reasons that lead us to believe this finding is mostly due to the difference in matrimonial migration of males and females, as wives relocate at marriage more frequently than husbands do. We want to test this hypothesis further with the new data and independent methods. This should also allows us to test our findings on the relative variation between and within populations of autosomes, Y chromosome and mtDNA. X chromosomes should show another, predictable pattern. In all these situations we plan to use a variety of methods of statistical analysis, including new ones we have developed, based on the distribution of the number of mutants, and on their geography of mutants. We aim to reconstruct and date migrations during the expansion of modern humans in the last 100,000 years, and to understand more about the role of evolutionary factors, including mutation and selection.

这个子项目将致力于对大量新的多态性进行基因分型，其中一部分是由我们发现的，另一部分是由外部倡议发现的。我们计划对CEPH与我们合作开发的世界范围内的细胞系提供的dna进行基因分型，目的是了解人类进化的历史和经典进化因素（突变、自然选择、漂变和迁移）在决定人类遗传变异中的作用。基因分型方法将在本项目中开发，用于发现和测试新的遗传多态性，DHPLC（变性高效液相色谱法）。在相同的精度下，如果一种新的方法在成本上更有价值，它将被完善或被其他方法所取代。特别是，我们将分析整个线粒体DNA的变异（不包括已经被广泛探索的D-loop）。在新的项目开始时，我们预计已经产生了大约450个新的mtDNA snp。我们还想以同样的方式对大量的Y染色体突变进行分类，我们计划在另一项拨款NIH GM55273的支持下，从染色体上越来越多的Y染色体位置继续提供这些突变。选择一些已知的X染色体基因将在男性中进行类似的研究。我们已经证明，Y突变体在种群之间的差异几乎是mtDNA突变体的三倍。我们给出的理由使我们相信，这一发现主要是由于男性和女性在婚姻迁移方面的差异，因为妻子在婚姻中搬迁的频率比丈夫高。我们想用新的数据和独立的方法进一步检验这一假设。这也将使我们能够测试我们在常染色体、Y染色体和mtDNA群体之间和群体内部的相对变异的发现。X染色体应该呈现另一种可预测的模式。在所有这些情况下，我们计划使用各种统计分析方法，包括我们开发的基于突变体数量分布和突变体地理位置的新方法。我们的目标是重建和确定过去10万年现代人类在扩张过程中的迁移，并了解更多关于进化因素的作用，包括突变和选择。