METHODS FOR SINGLE NUCLEOTIDE POLYMORPHISMS

描述：（申请人摘要）该RFA要求30，000至300，000 基于单核苷酸多态性（SNP）的遗传标记， 在接下来的几年里创造的。 作为回应，我们提出了一个试点计划， 我们相信可以扩大到全基因组水平， 提供了一类特别重要的SNP：发生在cDNA中的SNP 序列（cSNP）。 许多cSNP可以从EST数据库中提取， 我们会尽量利用这些机会。 但是，我们也将填写 数据库中的漏洞有两种形式。 对于许多 大量表达的基因，没有多少个体被取样;许多 基因不完全被EST覆盖。 所以，我们将沿着 选择的cDNA序列的整个长度，在25个样本中， 不同种族的个体，推导出全长共有cDNA 当序列还不可用时。 我们的cSNP发现过程将 是顺序驱动的。 虽然这可能是最昂贵的方法， 它也是最全面的，因为它确保几乎所有共同的 这样一个彻底的方法是有道理的，因为最常见的 cSNP可能对基于人群的关联研究有用 这些计划是为了更好地理解 基因复杂的疾病 在这三年的时间里，我们将 重新测序500个基因，并为所有常见的cSNP创建标记， 在新的序列数据和现有EST数据的组合中发现。 我们 将创建cDNA资源，以更好地对全长cDNA进行采样， 顺序 我们将评估一种评分技术（TDI）， 有潜力可挖。 我们将开发软件， cSNP发现、标记创建和TDI评分的过程。

DESCRIPTION: (Applicant's abstract) This RFA calls for 30,000 to 300,000 genetic markers, based on single-nucleotide-polymorphisms (SNPs), to be created over the next few years. In response, we propose a pilot program that we believe can be scaled up to a whole-genome level, and which will provide a particularly important category of SNPs: those occurring in cDNA sequences (cSNPs). Many cSNPs can be extracted from the EST databases and we will exploit these as much as possible. However, we will also fill in the gaps in the databases, which come in two forms. For many of the less abundantly expressed genes, not many individuals have been sampled; and many genes are incompletely covered by ESTs. So, we will scan for cSNPs along the entire length of selected cDNA sequences, across a sample of 25 ethnically diverse individuals, deriving the full-length consensus cDNA sequence when one is not already available. Our cSNP discovery process will be sequence-driven. Although this is probably the most expensive approach, it is also the most comprehensive, as it ensures that nearly all common cSNPs will be found. Such a thorough approach is justifiable as most common cSNP are likely to be useful for the population-based association studies that are being planned in the growing efforts to understand genetically-complex diseases. Over the course of this 3 year grant, we will re-sequence 500 genes and create markers for all the common cSNPs that are found in this combination of new sequence data and existing EST data. We will create cDNA resources to better sample the full length of the cDNA sequence. We will evaluate a scoring technology (TDI) that has the potential to be arrayed. And we will develop software to facilitate the process of cSNP discovery, marker creation, and TDI scoring.