【正文】 rocedure: A large F2 or BC population, Only individuals rebinant at a QTLcontaining interval are subsequently phenotyped. 23:13 ? Requires only 2 generations . ? Requires very large samples . 23:13 SPh Experimental results 02460 20 40 60 80cMLODLesions density Paigen et al. BC SPhBC 23:13 重組后裔檢驗（ Rebinant progeny testing） 23:13 Rebinant progeny testing QTL Males, rebinant at an interval of interest, are progeny tested to check which QTL allele was retained. ?Requires only 3 generations. Efficient for dominant effects ?Requires large sample 23:13 Intervalspecific congenic strains 區(qū)間特異 同源異基因品系 23:13 Interval specific congenic strains (ISCS) QTL ISCS are produced by a series of backcrosses and intercrosses Requires very few individuals. Useful fro further studies Complicated and lengthy development process. 23:13 Rebinant inbred segregation test (RIST) P1 RI P2 x x F1,1 F1,2 F2,1 F2,2 23:13 Each selected RIL is backcrossed to each parent and then the BC1 is selfed and grown out for phenotypiing and genotyping in the QTL region. Because the QTL was previously mapped to this region, the BC to one of the parents will segregate while the other will not。 23:13 遠交系雜交 23:13 ? 遠交系雜交與 F2情形比較類似，但現(xiàn)在是兩個經(jīng)濟性狀存在差異的遠交系或品種進行異型雜交； ? 所有三代，包括祖代、 F1和 F2在多個標記位點都要進行標記基因型判型，但只有 F2個體獲得表型； ? F2個體的 QTL基因型（ 、 Qq、 qQ和 qq）的兩個等位基因不能區(qū)分那一個來自父親，那一個來自母親； ? 在遠交群體雜交，要考慮加性效應(yīng)、顯性效應(yīng)和父母親來源效應(yīng)（印記效應(yīng)）。 23:13 公畜單倍型重構(gòu) ? 確定每個 HS后代的信息標記，即確定公共父母親的那些標記是雜合的，且等位基因的傳遞是清楚的； ? 考慮某一個公共父母親的那一些相鄰標記對是雜合的； ? 計算出兩個相鄰位點等位基因能確定遺傳自公共父母親的后代數(shù)目； ? 利用期望最大法（ EM）在最小化重組數(shù)目的基礎(chǔ)上建立標記位點的連鎖相 23:13 多個半同胞家系 ? 對上面四個父母親的后代進行標記對比分析將不會檢測到QTL，因為 M和 m的差異為零，所以應(yīng)該考慮家系內(nèi)的嵌套分析。 23:13 ? NCP for the daughter design as: ? NCP for the granddaughter design as: ? Once the NCP parameters is calculated, power is derived as the probability that a noncentral variate exceeds the threshold from a central distribution. ? GDD is generally much more powerful than a daughter design 23:13 全同胞家系 ? 單個或多個大的全同胞家系在絕大部分物種內(nèi)都是不可能的，但檢測到 QTL的能力很強。). 2?23:13 ? The advantage of this likelihoodbased approach. ? The full maximum likelihood approach simultaneously estimates the IBD probabilities and the variance ponents, in a bined segregation analysis and linkage analysis framework. –―distribution method‖ –―expectation method‖ 23:13 ? So why is QTL mapping in general pedigrees not used more frequently, in particular in large, deep pedigrees? – IBD estimation in large pedigrees. – the unavailability of (userfriendly) software for the variance ponent estimation part of the analysis. – a finite budget. – the unavailability of DNA samples from most ancestors 23:13 IBD 估計 23:13 Perfect marker ? As in the case of sibpairs, IBD sharing using a fully informative marker is straightforward, because we can simply count the number of alleles that two relatives share by descent. ? At a location linked to a perfect marker, IBD probabilities can be calculated from the observed IBD probability at the marker, the average relationship between individuals, and the rebination rate between the marker and putative QTL position. 23:13 The general case: missing data and noninformative markers ? The marker information in plex pedigrees is often inplete. ? Unknown linkage phases, noninformative markers and/or missing marker genotypes plicate the calculation of Q. ? The calculation methods of Q are: – recursive algorithms, – correlation based algorithms – simulation based algorithms. 23:13 Implementation in Loki ? The multiplesite segregation sampler in Loki is a cleverly designed Gibbs sampler with ?batch updating‘. – – is the probability of the segregation indicators across n loci at the ith segregation conditional on all other segregation indicators and observed marker data. 23:13 ? A two step strategy to sample – The first step involves moving through the genome, calculati