Background: Macrosatellite repeats (MSRs), usually spanning hundreds of kilobases of genomic DNA, comprise a significant proportion of the human genome. Because of their highly polymorphic nature, MSRs represent an extreme example of copy number variation, but their structure and function is largely understudied. Here, we describe a detailed study of six autosomal and two X chromosomal MSRs among 270 HapMap individuals from Central Europe, Asia and Africa. Copy number variation, stability and genetic heterogeneity of the autosomal macrosatellite repeats RS447 (chromosome 4p), MSR5p (5p), FLJ40296 (13q), RNU2 (17q) and D4Z4 (4q and 10q) and X chromosomal DXZ4 and CT47 were investigated. Results: Repeat array size distribution analysis shows that all of these MSRs are highly polymorphic with the most genetic variation among Africans and the least among Asians. A mitotic mutation rate of 0.4-2.2% was observed, exceeding meiotic mutation rates and possibly explaining the large size variability found for these MSRs. By means of a novel Bayesian approach, statistical support for a distinct multimodal rather than a uniform allele size distribution was detected in seven out of eight MSRs, with evidence for equidistant intervals between the modes. Conclusions: The multimodal distributions with evidence for equidistant intervals, in combination with the observation of MSR-specific constraints on minimum array size, suggest that MSRs are limited in their configurations and that deviations thereof may cause disease, as is the case for facioscapulohumeral muscular dystrophy. However, at present we cannot exclude that there are mechanistic constraints for MSRs that are not directly disease-related. This study represents the first comprehensive study of MSRs in different human populations by applying novel statistical methods and identifies commonalities and differences in their organization and function in the human genome.

We discuss Bayesian inferential procedures within the family of instrumental variables regression models and focus on two issues: existence conditions for posterior moments of the parameters of interest under a flat prior and the potential of Direct Monte Carlo (DMC) approaches for efficient evaluation of such possibly highly non-elliptical posteriors. We show that, for the general case of m endogenous variables under a flat prior, posterior moments of order r exist for the coefficients reflecting the endogenous regressors’ effect on the dependent variable, if the number of instruments is greater than m +r, even though there is an issue of local non-identification that causes non-elliptical shapes of the posterior. This stresses the need for efficient Monte Carlo integration methods. We introduce an extension of DMC that incorporates an acceptance-rejection sampling step within DMC. This Acceptance-Rejection within Direct Monte Carlo (ARDMC) method has the attractive property that the generated random drawings are independent, which greatly helps the fast convergence of simulation results, and which facilitates the evaluation of the numerical accuracy. The speed of ARDMC can be easily further improved by making use of parallelized computation using multiple core machines or computer clusters. We note that ARDMC is an analogue to the well-known "Metropolis-Hastings within Gibbs" sampling in the sense that one ‘more difficult’ step is used within an ‘easier’ simulation method. We compare the ARDMC approach with the Gibbs sampler using simulated data and two empirical data sets, involving the settler mortality instrument of Acemoglu et al. (2001) and father's education's instrument used by Hoogerheide et al. (2012a). Even without making use of parallelized computation, an efficiency gain is observed both under strong and weak instruments, where the gain can be enormous in the latter case

A dynamic asset-allocation model is specified in probabilistic terms as a combination of return distributions resulting from multiple pairs of dynamic models and portfolio strategies based on momentum patterns in US industry returns. The nonlinear state space representation of the model allows efficient and robust simulation-based Bayesian inference using a novel non-linear filter. Combination weights can be cross-correlated and correlated over time using feedback mechanisms. Diagnostic analysis gives insight into model and strategy misspecification. Empirical results show that a smaller flexible model-strategy combination performs better in terms of expected return and risk than a larger basic model-strategy combination. Dynamic patterns in combination weights and diagnostic learning provide useful signals for improved modelling and policy, in particular, from a risk-management perspective.