Two groups of methods are being developed to fine-map quantitative trait loci (QTLs): identity-by-descent methods or methods using historical recombinations, and genetic chromosome
dissection methods or methods utilizing current recombinations. Here we propose two methods
that fall into the second group: contrast mapping and substitution mapping. A QTL has
previously been detected via linkage mapping in a half-sib design (granddaughter or daughter
design), and sires (grandsires) likely to be heterozygous at the QTL have been identified. A sire
(grandsire) and its recombinant offspring are then genotyped for a series of ordered markers
spanning the initial marker interval. Offspring are grouped by paternal multi-marker haplotype
with haplotypes differing in the location of the recombination event. In the contrast method,
contrasts between the phenotypic averages of haplotypes or offspring groups are calculated which
correspond to marker intervals within the original interval. The expected value of the contrast for
the true QTL interval is always maximum, hence the interval with maximum observed contrast is
assumed to contain the QTL. Alternative statistics for determining the interval most likely to
contain a QTL are presented for contrast mapping, as well as a bootstrap estimation of the
probability of having identified the correct interval. For an initial marker bracket of 20 cM and 10
additional equidistant markers, the probability of assigning the QTL to the correct 2 cM marker
interval or to a combined 4 cM interval was calculated. For substitution effects of 0·093, 0·232,
0·464, 0·696 and 0·928 (in additive genetic SD), power values near
0·14, 0·26, 0·48, 0·67 and 0·80
(0·25, 0·53, 0·86, 0·97 and 0·99)
are achieved for a family of 200 (1000) sons, respectively. In
substitution mapping, QTL segregation status of recombinant sons must be determined using
daughter genotyping. Combinations of two haplotypes with their segregation status are required to
assign the QTL to an interval. Probabilities of correct QTL assignment were calculated assuming
absence of the mutant QTL allele in dams of sons. For a 2 cM interval and a QTL at the
midpoint of an interval, power near 0·95 (0·90) is reached when the number of recombinant sons is
70 (60), or total number of sons is 424 (363). For QTL positions away from the midpoint, power
decreases but can be improved by combining marker intervals. For a QTL located halfway to the
midpoint, and 182 sons in a family resulting in 30 recombinant sons, probability is 0·94 for
assignment to either a 2 cM or a combined 4 cM interval. Effect of type I and type II errors in
segregation status determination on power of QTL assignment was found to be small. Errors in
segregation status due to QTL segregation in dams have an impact if the frequency of the mutant
QTL allele is intermediate to high.