Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 7, 2011
Publication Date: March 15, 2011
Citation: Li, H., Bradbury, P., Buckler IV, E.S., Ersoz, E., Wang, J. 2011. Joint QTL linkage mapping for multiple-cross mating design sharing one common parent. PLoS One. 6:e17573. Interpretive Summary: Quantitative trait loci (QTL) are locations on a chromosome where genetic variability results in measurable changes in a trait of interest. The nested association mapping (NAM) design is a genetic mating design that allows researchers to combine the strengths of two types of genetic mapping techniques, linkage mapping and association mapping, to locate QTL more accurately. Linkage mapping, performed on the offspring of two parents, is more likely to find quantitative trait loci QTL than association mapping but does not estimate the positions as accurately. This study investigates the properties of the NAM design in conjunction with a mapping method called joint inclusive composite interval mapping (JICIM). It does that by examining flowering time in maize and Arabidopsis NAM populations. A disadvantage of using real data is that only a few of the real QTL are known, making it difficult to determine whether or not the methods are providing correct answers. One solution is to use simulated data with known QTL sizes and positions, then determine how often the analysis is able to correctly identify them. Using simulated data, this research showed that that using JICIM with NAM populations is very effective for finding large and medium sized QTL and moderately effective at finding small QTL. This is an important result for researchers, as it provides information about the sizes of QTL that they can expect to detect using these methods and how accurately their positions can be determined.
Technical Abstract: Nested association mapping (NAM) is a novel genetic mating design that combines the advantages of linkage analysis and association mapping. This design provides opportunities to study the inheritance of complex traits, but also requires more advanced statistical methods. In this paper, we present the detailed algorithm of a QTL linkage mapping method suitable for genetic populations derived from NAM designs. This method is called joint inclusive composite interval mapping (JICIM). Simulations were designed on the detected QTL in a maize NAM population and an Arabidopsis NAM population so as to evaluate the efficiency of the NAM design and the JICIM method. Fifty-two QTL were identified in the maize population, explaining 89% of the phenotypic variance of days to silking, and nine QTL were identified in the Arabidopsis population, explaining 83% of the phenotypic variance of flowering time. Simulations indicated that the detection power of these identified QTL was consistently high, especially for large-effect QTL. For rare QTL having significant effects in only one family, the power of correct detection within the 5 cM support interval was around 80% for 1-day effect QTL in the maize population, and for 3-day effect QTL in the Arabidopsis population. For smaller-effect QTL, the power diminished, e.g., it was around 50% for maize QTL with an effect of 0.5 day. When QTL were linked at a distance of 5 cM, the likelihood of mapping them as two distinct QTL was about 70% in the maize population. When the linkage distance was 1 cM, they were more likely mapped as one single QTL at an intermediary position. Because it takes advantage of the large genetic variation among parental lines and the large population size, NAM is a powerful multiple-cross design for complex trait dissection. JICIM is an efficient and specialty method for the joint QTL linkage mapping of genetic populations derived from the NAM design.