Support vector machine for prediction of meiotic recombination hotspots and coldspots in Saccharomyces cerevisiae

A novel method for predicting hotspots and coldspots using support vector machine （SVM） based on statistical learning theory is developed. This method is applied to published 303 hot and 48 cold open reading frames （ORFs） in Saccharomyces cerevisiae. The sequence features of general dinucleotide abundance and dinucleotide abundance based on codon usage are extracted, and then the data sets are classified with different parameters and kernel functions combined with the method of two-fold cross validation. The result indicates that 87.47% accuracy can be reached when classifying hot and cold ORF sequences with the kernel of radial basis function combined with dinucleotide abundance based on codon usage.

The genome-wide meiotic recombination landscape in ciliates and its implications for crossover regulation and genome evolution

Meiotic recombination is essential for sexual reproduction and its regulation has been extensively studied in many taxa.However,genome-wide recombination landscape has not been reported in ciliates and it remains unknown how it is affected by the unique features of ciliates:the synaptonemal complex(SC)-independent meiosis and the nuclear dimorphism.Here,we show the recombination landscape in the model ciliate Tetrahymena thermophila by analyzing single-nucleotide polymorphism datasets from 38 hybrid progeny.We detect 1021 crossover(CO)events(35.8 per meiosis),corresponding to an overall CO rate of 9.9 cM/Mb.However,gene conversion by non-crossover is rare(1.03 per meiosis)and not biased towards G or C alleles.Consistent with the reported roles of SC in CO interference,we find no obvious sign of CO interference.CO tends to occur within germ-soma common genomic regions and many of the 44 identified CO hotspots localize at the centromeric or subtelomeric regions.Gene ontology analyses show that CO hotspots are strongly associated with genes responding to environmental changes.We discuss these results with respect to how nuclear dimorphism has potentially driven the formation of the observed recombination landscape to facilitate environmental adaptation and the sharing of machinery among meiotic and somatic recombination.

真核生物减数分裂重组热点的研究进展

真核生物减数分裂过程中基因组中某些区域会发生较其他区域高的重组频率,这些区域被称作减数分裂重组热点。该现象首先在酵母的研究中发现,重组区域因含有启动重组的特异位点,从而使基因组中呈现出重组不均匀分布的特征。重组热点还在真菌、玉米和人类等真核生物中发现。文章列举了不同真核生物体中具有代表性鉴别重组热点的方法,总结了目前减数分裂重组热点的研究现状,探讨了引起真核生物减数分裂重组活跃的因子和机制,并就当前存在的问题和今后发展的前景进行了讨论。

PRDM9在哺乳动物基因重组热点中的作用

PRDM9(PR domain containing9)是一种可催化组蛋白H3的4位赖氨酸(H3K4)发生三甲基化修饰的甲基转移酶,还拥有转录因子活性.PRDM9主要在生殖细胞的减数分裂初期表达,它的功能异常可导致不育的发生.哺乳动物PRDM9在C端的锌指结构具有进化快速的特征,而这个特征与基因重组热点的多样性相对应,一系列证据表明,PRDM9参与了基因重组热点的结合和重组的起始.这些进展对深入理解物种进化和基因重组机制具有十分重要的意义.

腓骨肌萎缩症1A型基因重组热点区和多态性研究

目的：了解中国人腓骨肌萎缩症 1A 型（CMT1A）重组交换热点区和远端 REP3795bp 位置的多态性。方法：应用 PCR酶切分析和短串联重复序列（STR）分析检测 30 例CMT1患者的 17p112-12 基因重复，根据特异性融合片段的检出率判断基因重复者交换的热点区是否位于 1.7Kb 区域；通过 PCR 产物的酶切证实多态性情况。结果：70% CMT1A 患者交换断点位于 1.7Kb 区域；国人远端 REP 3795bp 位置的多态性为 63.8%。 结论：中国大多数 CMT1A 患者的交换断点位于 1.7Kb 区域，该区域为交换的热点区。特异性融合片段的存在可做为临床诊断 CMT1A 基因重复的筛选方法。

ReDB:A meiotic homologous recombination rate database

Meiotic recombination occurs preferentially at certain regions in the genome referred to as hot spots which are important for generating genetic diversity and proper segregation of chromosomes during meiosis.Although observations concerning individual hotspots have given clues as to the mechanism of recombination initiation,the nature and causes of recombination rate variation in the genome are still little known.A rational solution is to estimate and rank recombination rates along the genome.Therefore,it is a high demand for a database that deposits and integrates those data to provide a systematical repository of genome-wide recombination rates.Homologous recombination hotspots database is a web-based database of meiotic recombination rates,which comprises enormous data and information of human,mouse,rat,D.melanogaster,C.elegans and yeast.Users can query the database in several alternative ways.The database stores various details for every sequence,such as chromosome number,hyperlinks to the respective reference,and the sequence in FASTA format.

人类白细胞抗原分子遗传中的基因重组

深入研究人类白细胞抗原(humanleucocyteantigen,HLA)基因重组的分子生物学特性,对于揭示其等位基因多样性形成的演化机理以及人体所具有的抵抗多样致病微生物的防御能力具有重要意义。国外学者通过家系调查研究、统计学分析等方法估算了HLA的重组频率,证实了一些重组发生的热点,并且对重组的单倍型特异性、序列基序特异性、性别特异性等进行了深入研究。本文就HLA重组的交换频率、重组热点以及其它特性的研究现状作一综述。

柯尔克孜族PPARG基因重组热点遗传定位及其与维吾尔族人群的比较分析

目的分析探讨柯尔克孜族和维吾尔族两个人群过氧化物酶体增殖物激活受体叫（PPARG）基因重组热点特征及连锁不平衡（LD）模式。方法采用基质辅助激光解吸电离飞行时间质谱（MALDI—TOF—MS）方法对2013年8月采自新疆克孜勒苏柯尔克孜自治州阿图什市哈拉峻乡柯尔克孜族50例2型糖尿病患者（糖尿病组）、50名健康对照居民（健康对照组）和2012年5月采自新疆南疆和田地区的50名维吾尔族健康对照居民（维吾尔健康对照组）血液样品进行PPARG基因的31个标签单核苷酸多态性（taqSNP）位点的基因分型，采用HotspotFisher和Haploview软件推断该两个族群的PPARG基因重组热点特征及其LD模式。结果柯尔克孜糖尿病组、健康对照组和维吾尔健康对照组均有18个tagSNP相同（rs1151999、rs1175540、rs1875796、rs1899951、rs2292101、rs2921190、rs29383977、29592727、rs29592737、rs29721627、rs38568067 rs41352477、rs41352757、rs7091517 rs41353547、rs6805419、rs17036700、rs4135304），并在组间各个位点具有较高的重组率。LD分析结果显示，柯尔克孜健康对照组5个单体域的连锁不平衡系数（D’）=1，处于完全的连锁不平衡状态，不发生重组。柯尔克孜糖尿病组5个单体域的连锁不平衡系数D’0．91，D’〈1，说明两个位点间发生过重组。维吾尔健康对照组各4个单体域的连锁不平衡系数D’1，处于完全的连锁不平衡状态，也说明此区域无重组热点。柯尔克孜族、维吾尔族PPARG重组热点图谱与HapMap图比较发现存在明显差异，在HapMap重组热点谱图中有6个重组热点，柯尔克孜族PPARG重组热点图谱最后5个SNP显示较低的重组率，而维吾尔族PPARG基因重组热点图谱中未发现重组热点。结论在同一种族的糖尿病组与健康对照组或不同人群中在染色体某些区域的重组率变化可能存在很大差异，可能存在种群特异性的重组热点或同一热点位置的重组强度各不相同。

基于多信息融合的酵母重组冷热点预测

减数分裂重组并非均匀发生在基因组上,而是在一些区域有着较高的重组频率(重组热点),在另一些区域重组频率较低(重组冷点).重组的发生不仅与序列特征有关,还依赖于染色质的结构.准确鉴定重组热点和冷点对于认识重组发生的分子机制以及基因组进化规律具有重要意义.本文首先在实验数据的基础上识别2 kb尺度的重组冷热点,然后采用多样性增量结合二次判别分析(IDQD)和支持向量机(SVM)算法,基于一系列与DNA序列、结构及其热力学稳定性以及染色质结构相关的特征对酵母的重组冷热点进行了分类预测.结果表明,预测模型能够有效区分重组冷热点;从预测结果的敏感性、特异性和总精度来看,IDQD算法优于SVM算法.