The efficiency of designs for fine-mapping of quantitative trait loci using combined linkage disequilibrium and linkage

Abstract

-In a simulation study, different designs were compared for efficiency of finemapping of QTL. The variance component method for fine-mapping of QTL was used to estimate QTL position and variance components. The design of many families with small size gave a higher mapping resolution than a design with few families of large size. However, the difference is small in half sib designs. The proportion of replicates with the QTL positioned within 3 cM of the true position is 0.71 in the best design, and 0.68 in the worst design applied to 128 animals with a phenotypic record and a QTL explaining 25% of the phenotypic variance. The design of two half sib families each of size 64 was further investigated for a hypothetical population with effective size of 1000 simulated for 6000 generations with a marker density of 0.25 cM and with marker mutation rate 4 × 10 −4 per generation. In mapping using bi-allelic markers, 42∼55% of replicated simulations could position QTL within 0.75 cM of the true position whereas this was higher for multi allelic markers (48∼76%). The accuracy was lowest (48%) when mutation age was 100 generations and increased to 68% and 76% for mutation ages of 200 and 500 generations, respectively, after which it was about 70% for mutation ages of 1000 generations and older. When effective size was linearly decreasing in the last 50 generations, the accuracy was decreased (56 to 70%). We show that half sib designs that have often been used for linkage mapping can have sufficient information for fine-mapping of QTL. It is suggested that the same design with the same animals for linkage mapping should be used for fine-mapping so gene mapping can be cost effective in livestock populations.quantitative trait loci / fine-mapping / restricted maximum likelihood / simulation / designs

Power of QTL mapping experiments in commercial Atlantic salmon populations, exploiting linkage and linkage disequilibrium and effect of limited recombination in males

“…The observed increase in the power of LDLA over LA concurs with the results of Lee and van der Werf (2004). They simulated a QTL explaining 25% of the phenotypic variance segregating in a population of 128 individuals, belonging to between 2 and 64 half-sib families (ie between 64 and 2 individuals per half-sib family).…”

Efficiency of population structures for mapping of Mendelian and imprinted quantitative trait loci in outbred pigs using variance component methods

“…Additional value of LD is therefore limited for the 10 cM map as was observed in this study. The result based on the 2 cm map showed that LD information is of added value confirming the results obtained by Lee and van der Werf [13]. The map distance used in that study was 1 cM between markers.…”

“…In case the QTL-allele is rare more parents should be used to increase the chance of including segregating families. The results by Lee and van der Werf [13] based on full sib or half sib pedigrees also indicated that the number of families should be balanced with family size for the highest accuracy. Van der Beek et al [1] used a deterministic approach to estimate the power of different designs.…”

“…The size of a region that is IBD can be calculated from c = 1/(2 * mutation age) [13]. In this study c is 1/(2 * 100) = 0.005 M, i.e.…”

“…Usually there is a trade-off between the number of animals and the number of markers to be genotyped to keep the genotyping cost within limits. Changing the population structure will influence the ability to identify significant QTL [1,13,14].…”