Fine mapping and replication of QTL in outbred chicken advanced intercross lines

We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight.Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL.Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.In domestic animal populations, F2 crosses between divergently selected outbred lines are commonly used to map QTL [1-3]. However, only one generation of recombination occurs, in an F2 pedigree (gametes of the F1 generation) and linkage disequilibrium (LD) can be strong along the chromosomes. This long-range LD can be used to detect associations between QTL and markers even at a low marker density, e.g. one marker per 10 or 20 centiMorgans (cM) [1,4]. However, because of the extensive LD, using an F2 design results in large confidence intervals for QTL locations [5] that potentially contain hundreds of genes.To map QTL with a higher resolution,