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云之南

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专业背景:计算机科学 研究方向与兴趣: JavaEE-Web软件开发, 生物信息学, 数据挖掘与机器学习, 智能信息系统 目前工作: 基因组, 转录组, NGS高通量数据分析, 生物数据挖掘, 植物系统发育和比较进化基因组学

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SNP  

2011-05-31 11:46:26|  分类: 遗传与基因组学 |  标签: |举报 |字号 订阅

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http://baike.baidu.com/view/546117.htm

http://en.wikipedia.org/wiki/Single-nucleotide_polymorphism

 

SNP-单核苷酸多态性(SNP)
  全称Single Nucleotide Polymorphisms,是指在基因组上单个核苷酸的变异,形成的遗传标记,其数量很多,多态性丰富。指在基因组上单个核苷酸的变异,包括置换、颠换、缺失和插入。从理论上来看每一个SNP 位点都可以有4 种不同的变异形式,但实际上发生的只有两种,即转换和颠换,二者之比为2 :1。SNP 在CG序列上出现最为频繁,而且多是C转换为T ,原因是CG中的C 常为甲基化的,自发地脱氨后即成为胸腺嘧啶。一般而言,SNP 是指变异频率大于1 %的单核苷酸变异。在人类基因组中大概每1000 个碱基就有一个SNP ,人类基因组上的SNP 总量大概是3 ×10E6 个 。
  因此,SNP成为第三代遗传标志,人体许多表型差异、对药物或疾病的易感性等等都可能与SNP有关。
  现在普遍认为SNP研究是人类基因组计划走向应用的重要步骤。这主要是因为SNP将提供一个强有力的工具,用于高危群体的发现、疾病相关基因的鉴定、药物的设计和测试以及生物学的基础研究等。 SNP在基因组中分布相当广泛,近来的研究表明在人类基因组中每300碱基对就出现一次。大量存在的SNP位点,使人们有机会发现与各种疾病,包括肿瘤相关的基因组突变;从实验操作来看,通过SNP发现疾病相关基因突变要比通过家系来得容易;有些SNP并不直接导致疾病基因的表达,但由于它与某些疾病基因相邻,而成为重要的标记。SNP在基础研究中也发挥了巨大的作用,近年来对Y染色体SNP的分析,使得在人类进化、人类种群的演化和迁徙领域取得了一系列重要成果。
  单核苷酸多态性(single nucleotide polymorphism,SNP),主要是指在基因组水平上由单个核苷酸的变异所引起的DNA序列多态性。它是人类可遗传的变异中最常见的一种。占所有已知多态性的90%以上。SNP在人类基因组中广泛存在,平均每500~1000个碱基对中就有1个,估计其总数可达300万个甚至更多。
  SNP所表现的多态性只涉及到单个碱基的变异,这种变异可由单个碱基的转换(transition)或颠换(transversion)所引起,也可由碱基的插入或缺失所致。但通常所说的SNP并不包括后两种情况。
  理论上讲,SNP既可能是二等位多态性,也可能是3个或4个等位多态性,但实际上,后两者非常少见,几乎可以忽略。因此,通常所说的SNP都是二等位多态性的。这种变异可能是转换(C T,在其互补链上则为G A),也可能是颠换(C A,G T,C G,A T)。转换的发生率总是明显高于其它几种变异,具有转换型变异的SNP约占2/3,其它几种变异的发生几率相似。Wang等的研究也证明了这一点。转换的几率之所以高,可能是因为CpG二核苷酸上的胞嘧啶残基是人类基因组中最易发生突变的位点,其中大多数是甲基化的,可自发地脱去氨基而形成胸腺嘧啶。
  在基因组DNA中,任何碱基均有可能发生变异,因此SNP既有可能在基因序列内,也有可能在基因以外的非编码序列上。总的来说,位于编码区内的SNP(coding SNP,cSNP)比较少,因为在外显子内,其变异率仅及周围序列的1/5。但它在遗传性疾病研究中却具有重要意义,因此cSNP的研究更受关注。
  从对生物的遗传性状的影响上来看,cSNP又可分为2种:一种是同义 cSNP(synonymous cSNP),即SNP所致的编码序列的改变并不影响其所翻译的蛋白质的氨基酸序列,突变碱基与未突变碱基的含义相同;另一种是非同义cSNP(non- synonymous cSNP),指碱基序列的改变可使以其为蓝本翻译的蛋白质序列发生改变,从而影响了蛋白质的功能。这种改变常是导致生物性状改变的直接原因。cSNP中约有一半为非同义cSNP。
  先形成的SNP在人群中常有更高的频率,后形成的SNP所占的比率较低。各地各民族人群中特定SNP并非一定都存在,其所占比率也不尽相同,但大约有85%应是共通的。
  SNP自身的特性决定了它更适合于对复杂性状与疾病的遗传解剖以及基于群体的基因识别等方面的研究:
  1、 SNP数量多,分布广泛。据估计,人类基因组中每1000个核苷酸就有一个SNP,人类30亿碱基中共有300万以上的SNPs。SNP 遍布于整个人类基因组中,根据SNP在基因中的位置,可分为基因编码区SNPs(Coding-region SNPs,cSNPs)、基因周边SNPs(Perigenic SNPs,pSNPs)以及基因间SNPs(Intergenic SNPs,iSNPs)等三类。
  2、 SNP适于快速、规模化筛查。组成DNA的碱基虽然有4种,但SNP一般只有两种碱基组成,所以它是一种二态的标记,即二等位基因(biallelic)。 由于SNP的二态性,非此即彼,在基因组筛选中SNPs往往只需+/-的分析,而不用分析片段的长度,这就利于发展自动化技术筛选或检测SNPs。
  3、 SNP等位基因频率的容易估计。采用混和样本估算等位基因的频率是种高效快速的策略。该策略的原理是:首先选择参考样本制作标准曲线,然后将待测的混和样本与标准曲线进行比较,根据所得信号的比例确定混和样本中各种等位基因的频率。
  4、 易于基因分型。SNPs 的二态性,也有利于对其进行基因分型。对SNP进行基因分型包括三方面的内容:(1)鉴别基因型所采用的化学反应,常用的技术手段包括:DNA分子杂交、引物延伸、等位基因特异的寡核苷酸连接反应、侧翼探针切割反应以及基于这些方法的变通技术;(2)完成这些化学反应所采用的模式,包括液相反应、固相支持物上进行的反应以及二者皆有的反应。(3)化学反应结束后,需要应用生物技术系统检测反应结果。

 

 SNV和SNP之间有什么区别?

SNP和SNV: SNP是单核苷酸多态性,single nucleotide polymorphism,是在群体中的概念。现在肿瘤中发现的大量单个碱基的改变,如果没进一步在群体中验证过,应该称为SNV,single nucleotide variation 。

A single-nucleotide polymorphism (SNP, pronounced snip) is a DNA sequence variation occurring when a single nucleotideA, T, C, or G — in the genome (or other shared sequence) differs between members of a biological species or paired chromosomes in an individual. For example, two sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. In this case we say that there are two alleles: C and T. Almost all common SNPs have only two alleles.

Within a population, SNPs can be assigned a minor allele frequency — the lowest allele frequency at a locus that is observed in a particular population. This is simply the lesser of the two allele frequencies for single-nucleotide polymorphisms. There are variations between human populations, so a SNP allele that is common in one geographical or ethnic group may be much rarer in another.


Contents
[hide]
1 Types
2 Use and importance
3 Examples
4 Databases
5 Nomenclature
6 See also
7 Notes
8 References
9 External links

[edit] Types
Types of SNPs

Non-coding region
Coding region
Synonymous
Nonsynonymous
Missense
Nonsense

Single nucleotide polymorphisms may fall within coding sequences of genes, non-coding regions of genes, or in the intergenic regions between genes. SNPs within a coding sequence do not necessarily change the amino acid sequence of the protein that is produced, due to degeneracy of the genetic code.

A SNP in which both alleles produce the same polypeptide sequence is called a synonymous polymorphism (sometimes called a silent mutation) — if a different polypeptide sequence is produced they are replacement polymorphism. A replacement polymorphism change may be either missense, which results in a different amino acid, or nonsense, which results in a premature stop codon. Over half of known disease mutations are due to replacement polymorphism.[1]

SNPs that are not in protein-coding regions may still affect gene splicing, transcription factor binding, or the sequence of non-coding RNA. Gene expression effected by this type of SNP is referred to as an eSNP (expression SNP) and may be upstream or down stream from the gene.


[edit] Use and importance

Variations in the DNA sequences of humans can affect how humans develop diseases and respond to pathogens, chemicals, drugs, vaccines, and other agents. SNPs are also thought to be key enablers in realizing the concept of personalized medicine.[2] However, their greatest importance in biomedical research is for comparing regions of the genome between cohorts (such as with matched cohorts with and without a disease) in genome-wide association studies.

The study of SNPs is also important in crop and livestock breeding programs (see genotyping). See SNP genotyping for details on the various methods used to identify SNPs.

They are usually biallelic and thus easily assayed.[3] SNPs do not usually function individually, rather, they work in coordination with other SNPs to manifest a disease condition as has been seen in osteoporosis.[4]


[edit] Examples
rs6311 and rs6313 are SNPs in the HTR2A gene on human chromosome 13.
A SNP in the F5 gene causes a hypercoagulability disorder with the variant Factor V Leiden.
rs3091244 is an example of a triallelic SNP in the CRP gene on human chromosome 1.[5]
TAS2R38 codes for PTC tasting ability, and contains 6 annotated SNPs.[6]
[edit] Databases

As there are for genes, there are also bioinformatics databases for SNPs. dbSNP is a SNP database from National Center for Biotechnology Information (NCBI). SNPedia is a wiki-style database from a hybrid organization. The OMIM database describes the association between polymorphisms and, e.g., diseases in text form, the Human Gene Mutation Database provides gene mutations causing or associated with human inherited diseases and functional SNPs, while GWAS Central allows users to visually interrogate the actual summary-level association data in one or more genetic association studies.


[edit] Nomenclature

The nomenclature for SNPs can be confusing: several variations can exist for an individual SNP and consensus has not yet been achieved. One approach is to write SNPs with a prefix, period and greater than sign showing the wild-type and altered nucleotide or amino acid; for example, c.76A>T.[7][8][9]


 

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