Robust estimation of local genetic ancestry in admixed populations using a nonparametric Bayesian approach.

We present a new haplotype-based approach for inferring local genetic ancestry of individuals in an admixed population. Most existing approaches for local ancestry estimation ignore the latent genetic relatedness between ancestral populations and treat them as independent. In this article, we exploit such information by building an inheritance model that describes both the ancestral populations and the admixed population jointly in a unified framework. Based on an assumption that the common hypothetical founder haplotypes give rise to both the ancestral and the admixed population haplotypes, we employ an infinite hidden Markov model to characterize each ancestral population and further extend it to generate the admixed population. Through an effective utilization of the population structural information under a principled nonparametric Bayesian framework, the resulting model is significantly less sensitive to the choice and the amount of training data for ancestral populations than state-of-the-art algorithms. We also improve the robustness under deviation from common modeling assumptions by incorporating population-specific scale parameters that allow variable recombination rates in different populations. Our method is applicable to an admixed population from an arbitrary number of ancestral populations and also performs competitively in terms of spurious ancestry proportions under a general multiway admixture assumption. We validate the proposed method by simulation under various admixing scenarios and present empirical analysis results from a worldwide-distributed dataset from the Human Genome Diversity Project.

The role of androgens in fetal growth: observational study in two genetic models of disordered androgen signalling.

OBJECTIVE: To examine the role of androgens on birth weight in genetic models of altered androgen signalling. SETTING: Cambridge Disorders of Sex Development (DSD) database and the Swedish national screening programme for congenital adrenal hyperplasia (CAH). PATIENTS: (1) 29 girls with XY karyotype and mutation positive complete androgen insensitivity syndrome (CAIS); (2) 43 girls and 30 boys with genotype confirmed CAH. MAIN OUTCOME MEASURES: Birth weight, birth weight-for-gestational-age (birth weight standard deviation score (SDS)) calculated by comparison with national references. RESULTS: Mean birth weight SDS in CAIS XY infants was higher than the reference for girls (mean, 95% CI: 0.4, 0.1 to 0.7; p=0.02) and was similar to the national reference for boys (0.1, -0.2 to 0.4). Birth weight SDS in CAH girls was similar to the national reference for girls (0.0, -0.2 to 0.2) and did not vary by severity of gene mutation. Birth weight SDS in CAH boys was also similar to the national reference for boys (0.2, -0.2 to 0.6). CONCLUSION: CAIS XY infants have a birth weight distribution similar to normal male infants and birth weight is not increased in infants with CAH. Alterations in androgen signalling have little impact on birth weight. Sex dimorphism in birth size is unrelated to prenatal androgen exposure.

A species conserving genetic algorithm for multimodal function optimization

This paper introduces a new technique called species conservation for evolving parallel subpopulations. The technique is based on the concept of dividing the population into several species according to their similarity. Each of these species is built around a dominating individual called the species seed. Species seeds found in the current generation are saved (conserved) by moving them into the next generation. Our technique has proved to be very effective in finding multiple solutions of multimodal optimization problems. We demonstrate this by applying it to a set of test problems, including some problems known to be deceptive to genetic algorithms.