QTL定位的原理和方法课件.ppt

Genome wide association using haplotypes * IBD LD mapping * Combined LD-LA mapping Authors investigating the extent of LD in both cattle and sheep were somewhat surprised/alarmed to find not only was LD highly variable across any particular chromosome, but there was even significant LD between markers which were not even on the same chromosome! * Combining method * If the common ancestor occurs within the known pedi-gree, then IBD probability can be calculated from the markers by linkage analysis (LA) If the common ances-tor is outside the known pedigree it is a source of LD.In this case the probability that the QTL alleles are IBD is calculated from the similarity between the marker haplotypes, i.e., which marker alleles have both haplo-types in common * Variance components can be estimated using maximum likelihood or restricted maximum likelihood (REML), The log-likelihood function is: The assumed mean and variance structure of the observations : Q is the IBD matrix : * The distribution of the test statistics are, asymptotically, a mixture of zero (with probability ?) and a with 1 degree of freedom (also with probability of ?). * The advantage of this likelihood-based approach. The full maximum likelihood approach simultaneously estimates the IBD probabilities and the variance components, in a combined segregation analysis and linkage analysis framework. “distribution method” “expectation method” * 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 (user-friendly) software for the variance component estimation part of the analysis. a finite budget. the unavailability of DNA samples from most ancestors * IBD 估计 * 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