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利用连接读取测序技术从单个个体构建全基因组重组图谱。

Genome-wide recombination map construction from single individuals using linked-read sequencing.

机构信息

Friedrich Miescher Laboratory of the Max Planck Society, Max-Planck-Ring 9, 72076, Tübingen, Germany.

出版信息

Nat Commun. 2019 Sep 20;10(1):4309. doi: 10.1038/s41467-019-12210-9.

Abstract

Meiotic recombination rates vary across the genome, often involving localized crossover hotspots and coldspots. Studying the molecular basis and mechanisms underlying this variation has been challenging due to the high cost and effort required to construct individualized genome-wide maps of recombination crossovers. Here we introduce a new method, called ReMIX, to detect crossovers from gamete DNA of a single individual using Illumina sequencing of 10X Genomics linked-read libraries. ReMIX reconstructs haplotypes and identifies the valuable rare molecules spanning crossover breakpoints, allowing quantification of the genomic location and intensity of meiotic recombination. Using a single mouse and stickleback fish, we demonstrate how ReMIX faithfully recovers recombination hotspots and landscapes that have previously been built using hundreds of offspring. ReMIX provides a high-resolution, high-throughput, and low-cost approach to quantify recombination variation across the genome, providing an exciting opportunity to study recombination among multiple individuals in diverse organisms.

摘要

减数分裂重组率在基因组中存在差异,通常涉及局部的交叉热点和冷点。由于构建重组交叉点的个体化全基因组图谱需要高昂的成本和努力,因此研究这种变化的分子基础和机制一直具有挑战性。在这里,我们介绍了一种新的方法 ReMIX,该方法使用 Illumina 测序 10X Genomics 连接读取文库,从单个个体的配子 DNA 中检测交叉。ReMIX 重建单倍型并识别跨越交叉断点的有价值的稀有分子,从而可以定量确定减数分裂重组的基因组位置和强度。我们使用单个小鼠和棘鱼证明了 ReMIX 如何忠实地恢复先前使用数百个后代构建的重组热点和景观。ReMIX 提供了一种高通量、高分辨率且低成本的方法来量化全基因组中的重组变异,为研究多种生物中重组提供了令人兴奋的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/61bf/6754380/1b5481afb04d/41467_2019_12210_Fig1_HTML.jpg

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