Lecture 10 QTL Mapping 2: Outbred Populations

The major difference between QTL analysis using inbred-line crosses vs. outbred populations is that while the parents in the former are genetically uniform, parents in the latter are genetically variable. This distinction has several consequences. First, only a fraction of the parents from an outbred population are informative. For a parent to provide linkage information, it must be heterozygous at both a marker and a linked QTL, as only in this situation can a marker-trait association be generated in the progeny. Only a fraction of random parents from an outbred population are such double heterozygotes. With inbred lines, F1’s are heterozygous at all loci that differ between the crossed lines, so that all parents are fully informative. Second, there are only two alleles segregating at any locus in an inbred-line cross design, while outbred populations can be segregating any number of alleles. Finally, in an outbred population, individuals can differ in marker-QTL linkage phase, so that an M-bearing gamete might be associated with QTL allele Q in one parent, and with q in another. Thus, with outbred populations, marker-trait associations must be examined separately for each parent. With inbred-line crosses, all F1 parents have identical genotypes (including linkage phase), so one can simply average marker-trait associations over all offspring, regardless of their parents. Before considering the variety of QTL mapping methods for outbred populations, some comments on the probability that an outbred family is informative are in order. A parent is markerinformative if it is a marker heterozygote, QTL-informative if it is a QTL heterozygote, and simply informative if it is both. Unless both the marker and QTL are highly polymorphic, most parents will not be informative. Given the need to maximize the fraction of marker-informative parents, classes of marker loci successfully used with inbred lines may not be optimal for outbred populations. For example, SNPs are widely used in inbred lines, but these markers are typically diallelic and hence have modest polymorphism (at best). Microsatellite marker loci (STRs), on the other hand, are highly polymorphic and hence much more likely to yield marker-informative individuals.