Abstract
BackgroundLinkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature.MethodsWe 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.ResultsFive 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.ConclusionsOur 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.
Highlights
Linkage mapping is used to identify genomic regions affecting the expression of complex traits
In order to maximize the power to replicate Quantitative Trait Locus (QTL) detection and fine-mapping using an Advanced Intercross Lines (AIL) produced from outbred founders, we propose that the genotypes and phenotypes of all the individuals in the pedigree and not just of those from later generations should be collected and analysed
One of the low information content regions (Growth 9.1) was detected in both models. This makes it difficult to determine whether the loss of QTL with model B is due to false positive signals obtained with model A, or to the fact that marker information content is too low to distinguish between a QTL effect and a polygenic effect in a multigenerational intercross pedigree
Summary
Linkage mapping is used to identify genomic regions affecting the expression of complex traits. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. This approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature. To map QTL with a higher resolution, it is necessary to adopt a fine-mapping strategy that would ideally produce a QTL peak covering a chromosome region small enough to contain only a few genes. An AIL makes it possible to re-analyze and fine-map QTL originally detected in the F2 generation
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