Power and precision of QTL mapping in simulated multiple porcine F2 crosses using whole-genome sequence information

During the last two decades, many QTL (quantitative trait locus) mapping experiments in pigs have been conducted using F2 crosses established from two outbred founder breeds. The founder breeds were frequently chosen from the Asian and European type breeds. A combination of next-generation sequencing, SNP (single nucleotide polymorphism) genotyping technology using SNP-chips, and genotype imputation techniques, can be used to infer the sequence information of all F2 individuals in a cost-effective way. The aim of the present simulation study was to analyze the power and precision of genome-wide association studies (GWASs) with whole-genome sequence data in several types of F2 crosses, including pooled crosses.

Based on a common historical population, three breeds representing two European type breeds (EU1 and EU2) and one Asian type breed (AS) were simulated. Two F2 designs of 500 individuals each were simulated. The cross EU1xEU2 (ASxEU2) was simulated using the phylogenetically closely related breeds EU1 and EU2 (or distantly related breeds AS and EU2) as the founder breeds. The simulated genomes comprised ten chromosomes, each with a length of 1 Morgan and whole-genome sequence information. A polygenic trait with a heritability of 0.5, which was affected by approximately 20 QTL per Morgan, was simulated. GWASs were conducted using single marker mixed linear models, either within the crosses or in their pooled datasets. Additionally, the studies were conducted in the breed EU2, which was a founder breed in both simulated crosses.

The power to map QTL was high (low) in the ASxEU2 (EU1xEU2) cross and was highest when the data of both crosses were analyzed jointly. By contrast, the mapping precision was the highest in the EU1xEU2 cross. Pooling data led to a precision that was in between the precision of the EU1xEU2 cross and the ASxEU2 cross. A higher mapping precision was observed for QTL segregating within a founder breed.

These results suggest that the existing F2 crosses are promising databases for QTL mapping when the founder breeds are closely related or several crosses can be pooled. This conclusion is particularly applicable for QTL that segregate in a founder breed.