A tool for haplotype reconstruction from polyploid genomes

在过去的十年里，一些植物、动物、真菌和卵菌的基因组序列已经被阐明。全基因组知识的这一史无前例的飞跃使种群遗传学家拥有了工具，以显著提高分辨率来解决与种群动态有关的基本问题。一旦获得高质量的基因组序列，研究人员就可以使用下一代测序技术和高效的比对方法快速重建同一物种中的个体基因组。随后种群内个体之间的比较使得快速的基因图谱能够在整个基因组尺度上解决复杂的种群动态问题。然而，利用下一代测序进行基因组重测序、群体遗传学和基因定位的方法仍然局限于多倍体物种，包括几个重要的作物物种，如小麦(六倍体)和马铃薯(四倍体)，以及作物病原菌如致病疫霉。这些局限性是因为与二倍体生物体相比，操纵多倍体基因组序列的复杂性。鉴于关联作图和种群研究依赖于单倍型重建，多倍体一直是基础和应用研究进展的主要制约因素。目前的方法不能从短的读取序列中重建可靠的多倍体生物体的单倍型。因此，需要一种能够从短的测序读数中准确地重建单倍型的方法。在这项建议中，我们的目标是开发一种方法，利用最近发展的连锁方法重建多倍体物种的单倍型。在这个项目完成后，单倍型重建算法将能够充分利用各种多倍体物种的重新测序数据，包括重要的作物和病原体。这种方法也将适用于古代DNA，因为这些DNA往往非常碎片化，无法进行长时间阅读测序。古DNA的重建将有助于阐明过去的流行病和包括重要作物在内的几种生物的进化史。

A number of plant, animal, fungal, and oomycete genome sequences have been elucidated over the last decade. This unprecedented leap forward in genome-wide knowledge has empowered population geneticists with tools to address fundamental questions relating to population dynamics at a substantially enhanced resolution. Once high quality genome sequences become available, researchers can rapidly reconstruct the genomes of individuals within the same species using next generation sequencing technology and efficient alignment methods. The subsequent comparison between individuals within a population enables rapid gene mapping to address complex population dynamic questions at the whole genome scale. However, methods that exploit next generation sequencing for genome resequencing, population genetics, and gene mapping remain limited in polyploid species, which include several important crop species such as wheat (hexaploid) and potato (tetraploid) as well as crop pathogens such as Phytophthora infestans. The limitations are due to the complexity of manipulating polyploid genome sequences when compared to diploid organisms. Given that association mapping and population studies are reliant on haplotype reconstruction, polyploidy has been a major constraint for progress in both basic and applied research. Current methods are unable to reconstruct reliable haplotypes for polyploid organisms from short read sequences. Therefore, there is an important need for methods that can accurately recreate haplotypes from short sequencing reads. In this proposal, we aim to develop a method that reconstructs haplotypes of polyploid species using the recently developed linkage methods. At the completion of this project, the algorithm for haplotype reconstruction will enable the full exploitation of resequencing data for a variety of polyploid species, including important crops and pathogens. The method will be also applicable to ancient DNA that tends to be extremely fragmented preventing long read sequencing. The reconstruction of ancient DNA will help in elucidating past epidemics and the evolutionary history of several organisms, including important crops.