QTL fine-mapping with Recombinant-Inbred Heterogeneous Stocks and In-Vitro Heterogeneous Stocks
This page describes mapping strategies that we have devised in order to fine-map QTL using Heterogeneous Stocks whilst minimising genotyping cost. The method will appear in Mammalian Genome. This work is in collaboration with William Valdar and Jonathan Flint
ABSTRACT
We compare strategies to fine-map Quantitative Trait Loci (QTL) in mice using Heterogeneous Stocks (HS). We show that a panel of about 100 Recombinant Inbred Lines (RIL) derived from an HS, and which we call an RIHS, is ideally suited to fine-map QTL to very high resolution, without the cost of additional genotyping. We also investigate a strategy based on in-vitro fertilisation of large numbers of F1 offspring of HS males crossed with an inbred line (IVHS). This method requires some additional genotyping but avoids the breeding delays and costs associated with the construction of a RI panel. We show that QTL detection is higher using RIHS than with IVHS, and that it is independent of the number of RI lines, provided the total number of animals phenotyped is constant. However, fine-mapping accuracy is slightly better using IVHS. We also investigate the effects of varying the number of HS generations and using multiallelic microsatellites instead of SNPs. We find that quite modest generation times of 10-20 generations are optimal. Microsatellites are only superior to SNPs when the generation time is 30 or more and when the markers are widely spaced.
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