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Objective To evaluate the utility of subchondral bone texture from a baseline x-ray image for predicting 3-year knee osteoarthritis (OA) progression. Methods A total of 138 participants in the Prediction of Osteoarthritis Progression (POP) study were evaluated at baseline and 3 years. Fixed-flexion knee radiographs of the 248 non-replaced knees underwent fractal analysis of the medial subchondral tibial plateau using a commercially available software tool. OA progression was defined as a 1-grade change in joint space narrowing (JSN) or osteophyte based on a standardized knee atlas. Statistical analysis of fractal signatures was performed using a new method based on modeling the overall shape of fractal dimension versus radius curves. Results Baseline fractal signature of the medial tibial plateau was predictive of medial knee JSN progression (area under the curve [AUC] of Receiver Operating Characteristic plot of 0.75), but not progression based on osteophyte or progression of the lateral compartment. The traditional covariates (age, gender, body mass index, knee pain), general bone mineral content, and baseline joint space width fared little better than random variables for predicting OA progression (AUC 0.52–0.58). The maximal predictive model combined baseline fractal signature, knee alignment, traditional covariates, and bone mineral content (AUC 0.79). Conclusions We identified a prognostic marker of OA that is readily extracted from a plain radiograph by fractal signature analysis. The global shape approach to analyzing these data is a potentially efficient means of identifying individuals at risk of knee OA progression that needs to be validated in a second cohort.

Despite its importance to agriculture, the genetic basis of heterosis is still not well understood. The main competing hypotheses include dominance, overdominance, and epistasis. NC design III is an experimental design that has been used for estimating the average degree of dominance of quantitative trait loci (QTL) and also for studying heterosis. In this study, we first develop a multiple-interval mapping (MIM) model for design III that provides a platform to estimate the number, genomic positions, augmented additive and dominance effects, and epistatic interactions of QTL. The model can be used for parents with any generation of selfing. We apply the method to two data sets, one for maize and one for rice. Our results show that heterosis in maize is mainly due to dominant gene action, although overdominance of individual QTL could not completely be ruled out due to the mapping resolution and limitations of NC design III. For rice, the estimated QTL dominant effects could not explain the observed heterosis. There is evidence that additive 3 additive epistatic effects of QTL could be the main cause for the heterosis in rice. The difference in the genetic basis of heterosis seems to be related to open or self pollination of the two species. The MIM model for NC design III is implemented in Windows QTL Cartographer, a freely distributed software.H ETEROSIS (or hybrid vigor) is a phenomenon in which an F 1 hybrid has superior performance over its parents. It has been observed in many plant and animal species. The utilization of heterosis is responsible for the commercial success of plant breeding in many species and leads to the widespread use of hybrids in several crops and horticultural species. In maize, the most notable example, heterosis is the primary reason for the success of commercial industry (Stuber et al. 1992). In China, hybrid rice varieties showed $20% yield advantage over inbred varieties (Yuan 1992) and made a tremendous impact on rice production around the world.Despite its importance, the genetic basis of heterosis has been debated for almost one century and is still not explained satisfactorily. The dominance hypothesis (Davenport 1908;Bruce 1910;Keeble and Pellew 1910;Jones 1917) suggests that the alleles from one parent are dominant over the alleles from the other parent, and due to the cancelation of deleterious effects at multiple loci, the F 1 hybrid is superior to the parents.The overdominance hypothesis (East 1908;Shull 1908) assumes that the loci with heterozygous genotypes are superior to both homozygous parents. Epistasis is also frequently mentioned as a possible cause of heterosis.NC design III, or design III Robinson 1948, 1952), is an experimental design for estimating genetic variances and the average degree of dominance for quantitative trait loci (QTL) and has being used to study heterosis. Random F 2 individuals are taken from a population that originated by crossing two inbred lines. These individuals are backcrossed to both parental lines and a quantitative trait i...

Objective To evaluate subchondral bone trabecular integrity (BTI) from a radiograph as a predictor of knee osteoarthritis (OA) progression. Methods Longitudinal (baseline, 12- and 24-month) knee radiographs were available from 60 female subjects with knee OA. OA progression was defined by 12- and 24-month change in radiographic medial compartment minimal joint space width (JSW) and medial joint space area (JSA), and medial tibial and femoral cartilage volume from magnetic resonance imaging. Bone Trabecular Integrity (BTI) of the medial tibial plateau was analyzed by fractal signature analysis with a commercially available software. Receiver Operating Characteristic curves of BTI were used to predict 5% change in OA progression parameters. Results Individual terms (linear and quadratic) of baseline BTI of vertical trabeculae predicted knee OA progression based on 12- and 24-month change in JSA (p<0.01 for 24 months), 24-month change in tibial (p<0.05) but not femoral cartilage volume, and 24-month change in JSW (p=0.05). ROC utilizing both terms of baseline BTI predicted 5% change in the OA progression parameters over 24 months with high accuracy as reflected by the area under the curve (AUC) measures: JSW 81%, JSA 85%, tibial 75% and femoral 85% cartilage volume. Change in BTI was also significantly associated (p<0.05) with concurrent change in JSA over 12 and 24 months and change in tibial cartilage volume over 24 months. Conclusions BTI predicts structural OA progression as determined by radiographic and MRI outcomes. BTI may therefore be worthy of study as an outcome measure for OA studies and clinical trials.

Tremendous progress has been made in recent years on developing statistical methods for mapping quantitative trait loci (QTL) from crosses of inbred lines. In this chapter, we provide an introduction of composite interval mapping and multiple interval mapping methods for mapping QTL from inbred line crosses and also detailed instructions to perform the analyses in Windows QTL Cartographer. For each method, we discuss the meaning of each option in the analysis procedures and how to understand and interpret the mapping results through a work-out example.