专题一QTL及其定位方法esr.ppt
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1、专题一:QTL及其定位方法,QTL的概念 QTL检测方法 用于QTL定位的群体 统计方法 图距函数 QTL检测所需标记数预估,QTL的概念,1、A QTL is a segment of chromosome affecting the trait, not necessarily a single locus -D. S. Falconer et al, 1995 2、A quantitative trait loci(QTL) is defined as a single gene or a cluster of closely linked genes that have a large
2、 effect on a quantitative trait. -P. Sorensen, 2000,QTL的概念,3、QTL, quantitative trait locus, is a place (region) that affects trait in the genome. It could span several genes, one or more of which affects the trait, but it has become common to take QTL as equal to major gene. B. Kinghorn, 2000 理解:一个Q
3、TL指在基因组中占据一定染色体区域,控制同一性状的一组微效多基因的集合(基因簇)或单个基因。但目前的研究中大部分将QTL理解为单个基因(或主效基因)。一个数量性状可能受多个QTL影响;一个QTL也可能影响多个数量性状。,QTL的概念,QTL的特点(与传统的孟德尔因子比较) 结构更松散,一个QTL内各微效基因间可能有比孟德尔因子内高得多的重组率,因此一个QTL并不象一个孟德尔位点那样独立分离和有明显的性状效应。,QTL的概念,QTL概念提出的意义(D.S. Falconer-1995) 1、It could improve the efficacy of selective breeding,
4、especially for traits with low heritability or that can only be measured in one sex. 2、Transgenic technology might be applied to quantitative traits.,QTL的概念,3、In medicine, the identification of alleles causing predisposition to common multifactorial diseases could lead to improved methods of prevent
5、ion. 4、Quantitative genetic theory will be made more realistic when the numbers and properties of the genes are known, and the more realistic theories will improve our understanding of evolution (and/or the development of the quantitative traits).,QTL检测方法 Candidate gene approach(Hayes,2007),The cand
6、idate gene approach assumes that a gene involved in the physiology of the trait could harbour a mutation causing variation in that trait. The gene, or parts of the gene, are sequenced in a number of different animals, and any variations in the DNA sequences, that are found, are tested for associatio
7、n with variation in the phenotypic trait.,Candidate gene approach,There are two problems with the candidate gene approach: Firstly, there are usually a large number of candidate genes affecting a trait, so many genes must be sequenced in several animals and many association studies carried out in a
8、large sample of animals. Secondly, the causative mutation may lie in a gene that would not have been regarded a priori as an obvious candidate for this particular trait.,QTL检测方法,侯选基因途径的原理与方法: 1、选定侯选基因:根据现有的生物学、生理、生化知识,对数量性状的形成过程进行分析,预先选定一些基因作为数量性状的侯选基因。 2、数量性状记录和分子标记分析:PCR-RFLP,PCR-SSCP,MS,SNP等。,QTL
9、检测方法,3、关联分析(Association analysis) (1)Marker-based approach:按标记基因型对个体分组,然后对数量性状记录进行统计分析(t检验, 方差分析等) (2)Trait-based approach(Selective genotyping):根据性状表型值分别选取10-15%的高值个体和10-15%低值个体形成高低值群体,对两个群体中的个体进行基因型鉴定并对不同标记等位基因的频率进行统计检验(百分数差异显著性检验和Fishers精确检验等)。 (3)效应值估计:a, d。,QTL检测方法,关键:侯选基因的挑选及其准确性 优点:成本低(与连锁分析法
10、比较) 缺点:需具备数量性状形成的生物学、生理、生化等知识 经典例子:影响猪产仔数的ESR基因(M. Rothschild et al 1996),QTL检测方法,研究猪产仔数的意义 繁殖性状在猪生产中具有重要意义; 猪的繁殖性状遗传力低,常规选择效果不好; 不同猪群存在较大的产仔数差异;,QTL检测方法,选定ESR作为侯选基因的依据 类固醇类激素在繁殖过程中有重要作用; 人类中发现ESR的突变引起自发流产及乳腺癌; 转基因研究发现携带突变ESR的鼠与正常鼠繁殖力有重大变化; 经典的RFLP研究发现ESR存在多态性(A:3.7;B:4.3kb; 1.3kb cDNA Probe),QTL检测方
11、法,QTL检测方法,统计性状及分析方法 TNB-Total number born; NBA-Number born alive; ADG-Average daily gain; BF-Backfat thickness; FN-Number of functional nipples 模型:动物模型,Additive effect was estimated as the linear regression of litter size on ESR (for all alleles, P0.01). Dominance effect was estimated from the least
12、 squares means. a,b means P0.01; cd means P0.05,QTL检测方法,QTL检测方法,讨论: 研究结果表明:ESR位点存在变异,且其中一个最早在梅山猪中发现的等位基因与高窝仔数有显著关联。 尽管所有各胎的数据不足以排除ESR-B等位基因对产仔数的效应为非加性的,但其对猪头胎产仔数的效应肯定是加性的。 ESR-B等位基因在梅山合成系中约增加20%的窝仔数,每窝仔猪可产生约$15-30的利润(美国市场条件下)。,QTL检测方法,ESR-B等位基因在头胎及以后胎次中对窝产仔数效应的差异可能反映了该基因的效应在大龄母猪中能为环境效应所掩盖。 一个未解决的问题是
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