Large-Scale Low-Cost Genotyping for the Haplotype Map

描述（由申请人提供）：Perlegen Sciences提议使用其高通量基因分型平台在一年内成功地对270个HapMap样本进行至少225万个snp的基因分型，以补充HapMap Consortium的基因分型工作。我们独特的高密度寡核苷酸阵列基因分型平台非常适合这个大规模的项目，具有成本效益，准确和快速。例如，在今年的前六个月，我们进行了超过13亿次基因分型分析，仅在最后一个季度，我们就进行了超过7.7亿次基因分型分析，每月超过2.5亿次。随着基因分型效率的不断提高，我们继续降低检测的成本，最近的研究每个基因分型的成本不到一美分。我们在进行大规模研究方面拥有丰富的经验，同时保持较高的基因分型质量：在最近的一个内部项目中，我们进行了超过1.15亿次基因分型分析，基因分型质量评分为98.3%的完整性和99.5%的准确性。Perlegen Sciences是ENCODE HapMap项目的参与者，该项目对HapMap Consortium Centers的基因分型质量进行了评估。我们对所有已知的snp（包括Perlegen Sciences发现的snp和仅来自dbSNP的snp）进行了基因分型，没有事先选择，从HapMap Consortium在90个样本中选择的10个不同的基因组区域进行了基因分型。我们在事先不知道HapMap中心结果的情况下将数据提交给了HapMap Consortium。我们取得了优异的基因分型质量，呼出率为98.3%，并且，根据来自HapMap中心的公开数据，根据我们的结果进行比较的平台，一致性在97.63%和99.87%之间。我们独特的基因分型技术是高度灵活的：我们之前已经成功开发了约160万个snp的基因分型分析，分布在整个基因组中，包括Perlegen Sciences发现的snp和来自dbSNP的snp。此外，由于我们的平台是高度可扩展的，我们在如何设计和基因型snp方面是灵活的。例如，对于拟议的HapMap项目，我们可以预先为所有225万个snp设计基因分型分析，也可以在全年选择的snp批次中设计较小数量的基因分型分析。以我们目前每月超过2.5亿个基因型的吞吐量，在一年内完成至少6.48亿个snp的基因分型（即270个样本中的225万个snp，加上15个重复和3个空白），在HapMap项目规定的成本和质量下，我们完全有能力。

DESCRIPTION (provided by applicant): Perlegen Sciences proposes to use its high throughput genotyping platform to successfully genotype at least 2.25 million SNPs in 270 HapMap samples within one year, to supplement the HapMap Consortium's genotyping efforts. Our unique high-density oligonucleotide array-based genotyping platform is well suited to this large-scale project, being cost-effective, accurate, and rapid. For example, in the first six months of this year we performed over 1.3 billion genotyping assays, and in the last quarter alone we performed over 770 million genotyping assays, at a rate of more than 250 million per month. With constant improvements to genotyping efficiency, we continue to reduce the cost of our assays, with recent studies costing less than one cent per genotype. We have extensive experience performing very large scale studies, while maintaining high genotyping quality: in a recent internal project we performed over 115 million genotyping assays, with genotyping quality scores of 98.3% completeness and 99.5% accuracy. Perlegen Sciences was a participant in the ENCODE HapMap project, in which the genotyping quality of the HapMap Consortium Centers was evaluated. We genotyped all known SNPs (both those discovered by Perlegen Sciences and those derived solely from dbSNP), without prior selection, from ten diverse genomic regions chosen by the HapMap Consortium in 90 samples. We submitted the data to the HapMap Consortium without prior knowledge of the results from the HapMap Centers. We achieved excellent genotyping quality, with a call-rate of 98.3%, and, based on the publicly available data from the HapMap Centers, a concordance of between 97.63% and 99.87%, depending on the platform with which our results were compared. Our unique genotyping technology is highly flexible: we have previously developed successful genotyping assays for ~1.6 million SNPs, distributed across the entire genome, and including both SNPs discovered by Perlegen Sciences and those derived from dbSNP. In addition, because our platform is highly scalable, we are flexible in terms of how we design and genotype SNPs. For example, for the proposed HapMap project, we can either design genotyping assays for all 2.25 million SNPs up-front, or design smaller numbers of genotyping assays for batches of SNPs as they are chosen throughout the year. With our current throughput of over 250 million genotypes per month, completing the genotyping of at least 648 million SNPs (i.e. 2.25 million SNPs in 270 samples, plus 15 duplicates and 3 blanks) within one year, at the cost and quality specified by the HapMap Project, is well within our capacity.