QTL定位的原理和方法详解.ppt

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 * * 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, IBD probabilities can be calculated from the observed IBD probability at the marker, the average relationship between individuals, and the recombination rate between the marker and putative QTL position. * The general case: missing data and non-informative markers The marker information in complex pedigrees is often incomplete. Unknown linkage phases, non-informative markers and/or missing marker genotypes complicate the calculation of Q. The c