Suppr超能文献

基于互信息理论的多基因座连锁不平衡测度及其应用。

A multilocus linkage disequilibrium measure based on mutual information theory and its applications.

作者信息

Zhang Lei, Liu Jianfeng, Deng Hong-Wen

机构信息

Institute of Molecular Genetics and the Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, 710049, Xi'an, Shaanxi, People's Republic of China.

出版信息

Genetica. 2009 Dec;137(3):355-64. doi: 10.1007/s10709-009-9399-2. Epub 2009 Aug 26.

Abstract

Evaluating the patterns of linkage disequilibrium (LD) is important for association mapping study as well as for studying the genomic architecture of human genome (e.g., haplotype block structures). Commonly used bi-allelic pairwise measures for assessing LD between two loci, such as r(2) and D', may not make full and efficient use of modern multilocus data. Though extended to multilocus scenarios, their performance is still questionable. Meanwhile, most existing measures for an entire multilocus region, such as normalized entropy difference, do not consider existence of LD heterogeneity across the region under investigation. Additionally, these existing multilocus measures cannot handle distant regions where long-range LD patterns may exist. In this study, we proposed a novel multilocus LD measure developed based on mutual information theory. Our proposed measure described LD pattern between two chromosome regions each of which may consist of multiple loci (including multi-allele loci). As such, the proposed measure can better characterize LD patterns between two arbitrary regions. As potential applications, we developed algorithms on the proposed measure for partitioning haplotype blocks and for selecting haplotype tagging SNPs (htSNPs), which were helpful for follow-up association tests. The results on both simulated and empirical data showed that our LD measure had distinct advantages over pairwise and other multilocus measures. First, our measure was more robust, and can capture comprehensively the LD information between neighboring as well as disjointed regions. Second, haplotype blocks were better described via our proposed measure. Furthermore, association tests with htSNPs from the proposed algorithm had improved power over tests on single markers and on haplotypes.

摘要

评估连锁不平衡(LD)模式对于关联作图研究以及研究人类基因组的基因组结构(例如单倍型块结构)非常重要。常用的用于评估两个位点之间LD的双等位基因成对度量,如r(2)和D',可能无法充分有效地利用现代多基因座数据。尽管扩展到了多基因座情况,但其性能仍值得怀疑。同时,大多数现有的针对整个多基因座区域的度量,如归一化熵差,没有考虑所研究区域内LD异质性的存在。此外,这些现有的多基因座度量无法处理可能存在长程LD模式的远距离区域。在本研究中,我们提出了一种基于互信息理论开发的新型多基因座LD度量。我们提出的度量描述了两个染色体区域之间的LD模式,每个区域可能由多个位点组成(包括多等位基因位点)。因此,所提出的度量可以更好地表征两个任意区域之间的LD模式。作为潜在应用,我们基于所提出的度量开发了用于划分单倍型块和选择单倍型标签SNP(htSNP)的算法,这有助于后续的关联测试。模拟数据和实证数据的结果均表明,我们的LD度量相对于成对度量和其他多基因座度量具有明显优势。首先,我们的度量更稳健,能够全面捕捉相邻区域以及不相连区域之间的LD信息。其次,通过我们提出的度量可以更好地描述单倍型块。此外,使用所提出算法中的htSNP进行的关联测试比基于单个标记和单倍型的测试具有更高的效能。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验