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Estimating recombination rates from single nucleotide polymorphisms using summary statistics.

机译:使用汇总统计从单核苷酸多态性估计重组率。

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摘要

Meiotic recombination is a fundamental biological mechanism that transfers genetic material between homologous chromosomes. The knowledge of how recombination levels vary across a genome is crucial for the design of efficient association mapping studies as well as evolutionary inference studies, and is also of interest from the point of view of basic molecular biology. Since direct measurement of recombination fraction from experiments is technically challenging and genetic maps cannot provide fine-scale resolution, indirect estimation by applying population genetic methods to Single Nucleotide Polymorphism (SNP) data has proven to be a useful alternative.;Current meiotic models allow for two different kinds of recombination events called "crossing-over" and "gene-conversion". Crossing-over refers to the reciprocal exchange of large chromosomal fragments while gene-conversion refers to the transfer of short DNA tracts that are not accompanied by crossing-over. In this dissertation, we develop a novel method for jointly estimating both crossing-over and gene-conversion rates from population genetic data using summary statistics. Summary based methods are attractive in practice because these are extremely fast, flexible, and can directly provide confidence intervals for the estimated values.;The performance the new method was first tested on simulated datasets and compared with that of the pairwise composite likelihood method (Hudson 2001), that is widely used currently. Then, we applied our method to large human datasets resequenced by Perlegen Sciences and estimated recombination rates along the genome. In addition, we independently analyzed an Arabidopsis thaliana dataset sequenced by the Nordborg lab.;Our results with human data suggest that gene-conversion occurs frequently in the human genome relative to crossing-over. We obtained qualitatively similar results for Arabidopsis thaliana. Both human and Arabidopsis datasets seemed to deviate significantly from models where the ratio of conversion to crossing-over was uniform along the sequence. Over Mb scales, population genetic estimates of recombination rate in humans were strongly correlated with the estimates obtained from genetic maps.
机译:减数分裂重组是在同源染色体之间转移遗传物质的基本生物学机制。关于重组水平在整个基因组中如何变化的知识对于有效的关联作图研究和进化推断研究的设计至关重要,并且从基本分子生物学的角度来看也很重要。由于直接从实验中测量重组分数在技术上具有挑战性,并且遗传图谱无法提供精细的分辨率,因此通过将群体遗传方法应用于单核苷酸多态性(SNP)数据进行间接估计已被证明是一种有用的替代方法;当前的减数分裂模型允许两种不同的重组事件,称为“杂交”和“基因转化”。交叉是指大染色体片段的相互交换,而基因转化是指不伴随交叉的短DNA片段的转移。在本文中,我们开发了一种新的方法,可以使用汇总统计数据从种群遗传数据中共同估算交叉和基因转化率。基于摘要的方法在实践中很有吸引力,因为它们非常快速,灵活,并且可以直接为估计值提供置信区间。;首先在模拟数据集上测试了该新方法的性能,并将其与成对复合似然方法进行了比较(Hudson (2001),目前已被广泛使用。然后,我们将我们的方法应用于Perlegen Sciences重新排序的大型人类数据集,并估算了沿基因组的重组率。此外,我们独立分析了由Nordborg实验室测序的拟南芥数据集。我们的人类数据结果表明,相对于交叉而言,基因转换经常发生在人类基因组中。我们获得了拟南芥的定性相似结果。人类和拟南芥的数据集似乎都与模型的转化率大为不同,模型的转化率和交叉率沿序列是一致的。在Mb规模上,人类重组率的群体遗传学估计与从遗传图谱获得的估计密切相关。

著录项

  • 作者

    Padhukasahasram, Badri.;

  • 作者单位

    University of Southern California.;

  • 授予单位 University of Southern California.;
  • 学科 Biology Biostatistics.;Biology Genetics.;Statistics.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 139 p.
  • 总页数 139
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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