LDSplitDB：一个利用人类基因组数据研究MHC区域减数分裂重组热点的数据库。

LDSplitDB: a database for studies of meiotic recombination hotspots in MHC using human genomic data.

作者信息

Guo Jing, Chen Hao, Yang Peng, Lee Yew Ti, Wu Min, Przytycka Teresa M, Kwoh Chee Keong, Zheng Jie

机构信息

School of Computer Science and Engineering, Nanyang Technological University, Nanyang Ave, Singapore, 639798, Singapore.

Institute for Infocomm Research, Agency for Science, Technology & Research, 1 Fusionopolis Way, Singapore, 138632, Singapore.

出版信息

BMC Med Genomics. 2018 Apr 20;11(Suppl 2):27. doi: 10.1186/s12920-018-0351-0.

DOI:10.1186/s12920-018-0351-0

PMID:29697370

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5918432/

Abstract

BACKGROUND

Meiotic recombination happens during the process of meiosis when chromosomes inherited from two parents exchange genetic materials to generate chromosomes in the gamete cells. The recombination events tend to occur in narrow genomic regions called recombination hotspots. Its dysregulation could lead to serious human diseases such as birth defects. Although the regulatory mechanism of recombination events is still unclear, DNA sequence polymorphisms have been found to play crucial roles in the regulation of recombination hotspots.

METHOD

To facilitate the studies of the underlying mechanism, we developed a database named LDSplitDB which provides an integrative and interactive data mining and visualization platform for the genome-wide association studies of recombination hotspots. It contains the pre-computed association maps of the major histocompatibility complex (MHC) region in the 1000 Genomes Project and the HapMap Phase III datasets, and a genome-scale study of the European population from the HapMap Phase II dataset. Besides the recombination profiles, related data of genes, SNPs and different types of epigenetic modifications, which could be associated with meiotic recombination, are provided for comprehensive analysis. To meet the computational requirement of the rapidly increasing population genomics data, we prepared a lookup table of 400 haplotypes for recombination rate estimation using the well-known LDhat algorithm which includes all possible two-locus haplotype configurations.

CONCLUSION

To the best of our knowledge, LDSplitDB is the first large-scale database for the association analysis of human recombination hotspots with DNA sequence polymorphisms. It provides valuable resources for the discovery of the mechanism of meiotic recombination hotspots. The information about MHC in this database could help understand the roles of recombination in human immune system. DATABASE URL: http://histone.scse.ntu.edu.sg/LDSplitDB.

摘要

背景

减数分裂重组发生在减数分裂过程中，此时来自双亲的染色体交换遗传物质，以在配子细胞中产生染色体。重组事件倾向于发生在称为重组热点的狭窄基因组区域。其失调可能导致严重的人类疾病，如出生缺陷。尽管重组事件的调控机制仍不清楚，但已发现DNA序列多态性在重组热点的调控中起关键作用。

方法

为了便于对潜在机制进行研究，我们开发了一个名为LDSplitDB的数据库，它为重组热点的全基因组关联研究提供了一个综合且交互式的数据挖掘和可视化平台。它包含了千人基因组计划中主要组织相容性复合体（MHC）区域以及HapMap第三阶段数据集的预计算关联图谱，以及来自HapMap第二阶段数据集的欧洲人群的全基因组研究。除了重组图谱外，还提供了可能与减数分裂重组相关的基因、单核苷酸多态性（SNP）和不同类型表观遗传修饰的相关数据，以进行综合分析。为了满足快速增长的群体基因组学数据的计算需求，我们使用著名的LDhat算法编制了一个包含400个单倍型的查找表，用于重组率估计，该算法涵盖了所有可能的两位点单倍型配置。

结论

据我们所知，LDSplitDB是第一个用于人类重组热点与DNA序列多态性关联分析的大规模数据库。它为发现减数分裂重组热点的机制提供了宝贵资源。该数据库中有关MHC的信息有助于理解重组在人类免疫系统中的作用。数据库网址：http://histone.scse.ntu.edu.sg/LDSplitDB。