单核苷酸多态性的研究进展

随着基因组测序工作的进展,日益发现基因组中存在着数量庞大的单核苷酸多态性（single nucleotide polymorphisms,SNPs）。SNPs是指染色体基因组水平上单个核苷酸变异引起的DNA序列多态性,在人群中发生频率大于1％。SNPs有单碱基的转换（transition）、颠换（transversion）、插入、缺失等形式。转换：颠换约为2：1,25％的SNPs发生于CpG位点,发生C-T转换。SNPs在3’表达序列标签（express sequence tags,ESTs）中的分布要比其它基因组区域的少,研究表明,这与表达序列承受更大的选择压力是一致的。     

农业经济动物的SNPs研究进展

SNPs,即单核苷酸多态性,是指基因组DNA序列中由于单个核苷酸(A,T,C,G)的替换而引起的多态性。综述了SNPs分析方法及其在农业经济动物研究中的应用。     

基于JAVA WEB的SNPs分析平台的开发

单核酸多态性(SNPs)不仅提供了丰富的遗传变异信息,而且它对于进一步遗传信息的分析是至关重要的.本文以Atlas2工具为基础,,基于JAVA WEB开发了SNPs分析平台网站,使得Atlas2程序在线进行SNPs分析.SNPs分析平台网站不仅可以在一定程度上解决许多小型实验室关于SNPs分析所遇到的困难,而且使得许多非计算机专业的生物学者可以通过网站直接获取所需的SNP信息,为下一步基因变异的研究提供了基础.     

人类基因组1号、X、Y染色体CDS区多态性统计分析

依托GenBank数据库资源,分别对1号、X、Y染色体上CDS区的SNPs分布、类型和密度进行了初步分析。统计结果发现,AG(GA)和CT类型占优,分别各占30%以上;类型AC、AT、GT和CG统计频率在相同的数量级上,分别各占8%左右;并且这种分布频率不会随不同的染色体而变化。但是,SNPs在不同染色体上基因内的分布差异大。SNPs在Y染色体上的密度最小,在1号染色体上的密度最大。一般来说,SNPs的分布位置主要集中在内含子区,但是,在Y染色体上,外显子区的SNPs频数明显升高。     

多孔氧化铝膜调制的银纳米颗粒的表面增强荧光效应

采用氧化还原方法,在多孔氧化铝膜（Anodic Aluminum Oxide,AAO）模板中直接反应生成银纳米颗粒（SNPs）,制备出一种新型的AAO/SNPs纳米复合结构衬底.在532nm连续激光的激发下,研究了位于该纳米复合衬底上Rh6G分子的荧光增强效应.结果表明,AAO/SNPs纳米复合衬底对Rh6G的荧光发射强度与未经SNPs修饰的AAO对Rh6G的荧光发射强度相比,增强倍数可达6倍左右,而且荧光增强因子与AAO的孔径大小有关.此外本文还运用局域场增强理论对纳米复合体系中的荧光增强效应进行了分析讨论,并探讨了空间周期调制的金属纳米复合衬底对表面增强荧光效应的独特优点.     

新型的分子标记--SNPs

SNPs(Single nucleotide polymorphisms)是近年来发展起来的最有效的新一代分子标记。本文对SNPs的发展、基本原理、检测，以及在确定疾病相关基因研究中的应用进行了介绍和评述。     

Bayesian optimization algorithm-based methods searching for risk/protective factors

The risks of developing complex diseases are likely to be determined by single nucleotide polymorphisms (SNPs), which are the most common form of DNA variations. Rapidly developing genotyping technologies have made it possible to assess the influence of SNPs on a particular disease. The aim of this paper is to identify the risk/protective factors of a disease, which are modeled as a subset of SNPs (with specified alleles) with the maximum odds ratio. On the basis of risk/protective factor and the relationship between nucleotides and amino acids, two novel risk/protective factors (called k-relaxed risk/protective factors and weighted-relaxed risk/protective factors) are proposed to consider more complex disease-associated SNPs. However, the enormous amount of possible SNPs interactions presents a mathematical and computational challenge. In this paper, we use the Bayesian Optimization Algorithm (BOA) to search for the risk/protective factors of a particular disease. Determining the Bayesian network (BN) structure is NP-hard; therefore, the binary particle swarm optimization was used to determine the BN structure. The proposed algorithm was tested on four datasets. Experimental results showed that the algorithm proposed in this paper is a promising method for discovering SNPs interactions that cause/prevent diseases.     

Mapping and characterization of two relevance networks from SNP and gene levels

Variations of gene expression and DNA sequence are genetically associated. The goal of this study was to build genetic networks to map from SNPs to gene expressions and to characterize the two different kinds of networks. We employed mutual information to evaluate the strength of SNP–SNP and gene–gene associations based on SNPs identity by descent (IBD) data and differences of gene expressions. We applied the approach to one dataset of Genetics of Gene Expression in Humans, and discovered that both the SNP relevance network and the gene relevance network approximated the scale-free topology. We also found that 12.09% of SNP–SNP interactions matched 24.49% of gene–gene interactions, which was consistent with that of the previous studies. Finally, we identified 49 hub SNPs and 115 hub genes in their relevance networks, in which 27 hub SNPs were associated with 25 hub genes.     

翘嘴鳜淀粉酶基因SNPs和微卫星位点多态性的检测

本研究主要检测翘嘴鳜淀粉酶(amylase,AMY)基因的单核苷酸多态性(single nucleotide polymorphisms,SNP)和微卫星位点多态性.实验采用PCR产物直接测序法(PCR-direct sequencing,PCR-DS)检测翘嘴鳜AMY基因组序列的SNPs和微卫星位点,并使用创造限制酶切位点PCR法(created restriction sites PCR,CRS-PCR)和PCR-DS法对SNPs进行分型,应用聚丙烯酰胺凝胶电泳检测AMY基因微卫星位点的多态性.实验结果发现AMY基因第1内含子有一个SNP位点A1,第5内含子有3个SNPs位点(A2、A3和A4);此外,第5内含子中还存在一个微卫星位点B1,共检测到4个等位基因,有9种单倍型.在翘嘴鳜群体中,4个SNP位点呈中度遗传多样性,而微卫星位点表现出高度遗传多样性.     

云南哈尼族糜蛋白酶基因标签SNPs与原发性高血压的相关性研究

采用聚合酶链式反应-限制性片段长度多态性方法,对692例哈尼族人(高血压患者346例,正常对照个体346例)糜蛋白酶基因(chymase,CMA1)4个tag SNPs (rs1956921、rs1800876、rs5244和rs1885108)的多态性进行检测,并运用遗传模型研究CMA1基因tag SNPs与原发性高血压发生的相关性.结果显示,CMA1基因4个tag SNPs位点在混合人群和女性人群中均未显示出与原发性高血压的相关性;男性人群中,rs1800876位点基因型频率在对照组和高血压间的分布具有统计学意义(P=0.015),Logistic回归分析发现rs1800876位点TC和CC基因型携带者的患病风险显著降低(OR=0.59,95% CI为0.38~0.92,P=0.021),提示CMA1基因rs1800876位点与云南哈尼族男性原发性高血压发生相关.     

An SNP map of human chromosome 22

The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.     

A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms

We describe a map of 1.42 million single nucleotide polymorphisms (SNPs) distributed throughout the human genome, providing an average density on available sequence of one SNP every 1.9 kilobases. These SNPs were primarily discovered by two projects: The SNP Consortium and the analysis of clone overlaps by the International Human Genome Sequencing Consortium. The map integrates all publicly available SNPs with described genes and other genomic features. We estimate that 60,000 SNPs fall within exon (coding and untranslated regions), and 85% of exons are within 5 kb of the nearest SNP. Nucleotide diversity varies greatly across the genome, in a manner broadly consistent with a standard population genetic model of human history. This high-density SNP map provides a public resource for defining haplotype variation across the genome, and should help to identify biomedically important genes for diagnosis and therapy.     

An SNP map of the human genome generated by reduced representation shotgun sequencing

Most genomic variation is attributable to single nucleotide polymorphisms (SNPs), which therefore offer the highest resolution for tracking disease genes and population history. It has been proposed that a dense map of 30,000-500,000 SNPs can be used to scan the human genome for haplotypes associated with common diseases. Here we describe a simple but powerful method, called reduced representation shotgun (RRS) sequencing, for creating SNP maps. RRS re-samples specific subsets of the genome from several individuals, and compares the resulting sequences using a highly accurate SNP detection algorithm. The method can be extended by alignment to available genome sequence, increasing the yield of SNPs and providing map positions. These methods are being used by The SNP Consortium, an international collaboration of academic centres, pharmaceutical companies and a private foundation, to discover and release at least 300,000 human SNPs. We have discovered 47,172 human SNPs by RRS, and in total the Consortium has identified 148,459 SNPs. More broadly, RRS facilitates the rapid, inexpensive construction of SNP maps in biomedically and agriculturally important species. SNPs discovered by RRS also offer unique advantages for large-scale genotyping.     

一种新的分子标记--单核苷酸多态(SNP)

单核苷酸多态(SNP)为同一物种不同个体间染色体上遗传密码单个碱基的变化，是继限制性片段长度多态性(RFLP)、微卫星标记(SSR)之后的又一种新的分子标记，通常呈双等位基因多态。在此从SNP的特点、SNP的搜寻、SNP的确认与检测、SNP数据库、SNP作图、SNP的研究前景等方面对其研究进展进行综述。     

Construction of fine SNP haplotypes and haplotype blocks in 5 genes in the centromere of chromosome 15 in Chinese Han subjects

Recent advances have shown that the majorityof the nucleotide variation in human genome is single nucleo-tide polymorphisms (SNPs). Using SNPs each chromosomecan be divided into different haplotype blocks, and there arelimited common haplotypes in each block. This provides apowerful approach for whole genome scan for disease-asso-ciated genes/variants. However, most data available todayare based on the large-scale genomic analyses, data concern-ing individual genes for fine mapping with high density SNPsare relatively lacking. We have sequenced 7 genes and theirflanking regions, identified 34 novel SNPs, constructed highdensity SNP haplotypes and haplotype blocks in 5 genes inthe centromeric region of chromosome 15 in I00 ChineseHart subjects. Our results show that there is a great hetero-geneity in the haplotypes and haplotype block structureswithin and between these genes, which are in close physicalproximity. Data obtained in this study provide a useful toolfor candidate gene approach at the fine scale for identifyingdisease contributing variants in the genes/regions.     

Genome sequence, comparative analysis and haplotype structure of the domestic dog

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.     

A haplotype map of the human genome

Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.     

The diploid genome sequence of an Asian individual

Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics.     

单核苷酸多态性与肺癌关系的研究进展

癌症是严重威胁人类生存与健康的恶性疾病之一,而肺癌是癌症中发病率最高的一种。由于癌症难于治愈,死亡率极高,因此,预防是目前应对癌症的一个有效途径。单核苷酸多态性(SNP)广泛存在于人类基因组中,可作为检测癌易感基因的一个有效遗传标记。通过检查病例-对照人群的SNP差异来确定易感癌症的高危人群,起到预防癌症的作用。