Large-Scale Low-Cost Genotyping for the Haplotype Map

描述(申请人提供)：Perlegen Sciences计划利用其高通量基因分型平台，在一年内成功对270个HapMap样本中的至少225万个SNP进行基因分型，以补充HapMap联盟的基因分型工作。我们独特的基于寡核苷酸阵列的高密度基因分型平台非常适合这一大规模项目，具有成本效益、准确和快速的特点。例如，今年前六个月，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，我们继续降低我们的检测成本，最近的研究每种基因的成本不到1美分。我们在执行超大规模研究的同时保持高基因分型质量具有丰富的经验：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，基因分型质量分数达到98.3%的完成率和99.5%的准确率。PerLegen Sciences参与了ENCODE HapMap项目，在该项目中，对HapMap联盟中心的基因分型质量进行了评估。我们在没有事先选择的情况下，对所有已知的SNP(既有PerLegen Sciences发现的SNP，也有单独来自DBSNP的SNP)进行了基因分型，这些SNP来自HapMap Consortium在90个样本中选择的10个不同的基因组区域。我们在事先不知道HapMap中心的结果的情况下，将数据提交给了HapMap联盟。我们获得了很好的基因分型质量，呼叫率为98.3%，根据HapMap中心的公开数据，根据我们的结果比较的平台，一致性在97.63%到99.87%之间。我们独特的基因分型技术非常灵活：我们之前已经成功地开发了约160万个SNP的基因分型分析，这些SNP分布在整个基因组中，包括PerLegen Sciences发现的SNPs和来自DBSNP的SNP。此外，由于我们的平台具有高度可伸缩性，我们在如何设计SNPs和对SNP进行基因分型方面也很灵活。例如，对于拟议的HapMap项目，我们可以预先为所有225万个SNPs设计基因分型分析，或者在全年选择SNPs时为批次的SNPs设计较少数量的基因分型分析。以我们目前每月超过2.5亿个基因型的生产能力，在一年内以HapMap项目指定的成本和质量完成至少6.48亿个SNPs的基因分型(即270个样本中的225万个SNPs，加上15个重复和3个空白)，完全在我们的能力范围内。

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.