NEW VARIABLE POLYMORPHISMS

新的变量多态性

• 批准号: 6430859
• 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: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6430859
• 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.

该子项目将致力于对大量新的多态性进行基因分型，这些多态性部分是我们发现的，部分是由外部倡议发现的。我们计划对CEPH与我们合作开发的全球细胞系集合提供的DNA进行基因分型，目的是了解人类进化的历史以及经典进化因素（突变，自然选择，漂移和迁移）在决定人类遗传变异中的作用。基因分型方法将是在本计划项目过程中开发的用于发现和检测新的遗传多态性的方法，即变性高效液相色谱法（DHPLC）。如果一种新的方法证明在成本方面更有价值，并且具有相同的准确性，那么它将被其他方法完善或取代。特别是，我们将分析整个线粒体DNA的变异（不包括已经被广泛研究的D环）。在新项目开始时，我们预计将产生大约450个新的mtDNA SNP。我们还想用同样的方法，对大量的Y染色体突变体进行分型，我们计划在另一个基金NIH GM55273的支持下，继续提供这些突变体，这些突变体来自染色体上越来越多的Y染色体位置。将在男性中对选定数量的已知X染色体基因进行类似研究。我们已经证明，Y突变体在群体之间的变异几乎是mtDNA突变体的三倍。我们给出了一些理由，使我们相信这一发现主要是由于男性和女性婚姻迁移的差异，因为妻子在婚姻中的迁移比丈夫更频繁。我们希望用新的数据和独立的方法进一步验证这一假设。这也应该使我们能够测试我们的发现之间的相对变化和人口内的常染色体，Y染色体和mtDNA。X染色体应该显示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，包括我们开发的新方法，基于突变体数量的分布，以及突变体的地理分布。我们的目标是重建和确定现代人类在过去10万年中扩张过程中的迁移日期，并更多地了解进化因素的作用，包括突变和选择。