Models for lineal effects in rhesus group fissions

Gene distributions in daughter groups produced by three rhesus monkey group fissions are analyzed. Data employed are for the Tf, 6PGD, and CA II electrophoretic marker systems in the fissions producing new daughter groups F and M, F and O, and J and N in the Cayo Santiago rhesus colony. Wide variations in FST values were observed among the different markers in the various fissions. Overall, the observed FST values exceeded predictions of simple random fissioning models. However, on average, observations on electrophoretic markers fitted well with predicted values from lineal fissioning models. One of these lineal fissioning models, a simulation, incorporated the propagation of alleles in the matrilines of the fissioning groups. The second, an algebraic expression, utilized group sizes and average kinship values as parameters.     

Correlating Two Viral Load Assays with Known Detection Limits

A timely objective common to many HIV studies involves assessing the correlation between two different measures of viral load obtained from each of a sample of patients. This correlation has scientific utility in a number of contexts, including those aimed at a comparison of competing assays for quantifying virus and those aimed at determining the level of association between viral loads in two different reservoirs using the same assay. A complication for the analyst seeking valid point and interval estimates of such a correlation is the fact that both variables may be subject to left censoring due to values below assay detection limits. We address this problem using a bivariate normal likelihood that accounts for left censoring of two variables that may have different detection limits. We provide simulation results to evaluate sampling properties of the resulting correlation estimator and compare it with ad hoc estimators in the presence of nondetects. In an effort to obtain improved confidence interval properties relative to the Wald approach, we evaluate and compare profile likelihood-based intervals. We apply the methods to HIV viral load data on women and infants from a trial in Bangkok, Thailand, and we discuss an extension of the original model to accommodate interval censoring arising due to the study design.     

Information-theoretic indices and an approximate significance test for testing the molecular clock hypothesis with genetic distances

Distance-based phylogenetic methods are widely used in biomedical research. However, distance-based dating of speciation events and the test of the molecular clock hypothesis are relatively underdeveloped. Here I develop an approximate test of the molecular clock hypothesis for distance-based trees, as well as information-theoretic indices that have been used frequently in model selection, for use with distance matrices. The results are in good agreement with the conventional sequence-based likelihood ratio test. Among the information-theoretic indices, AICu is the most consistent with the sequence-based likelihood ratio test. The confidence in model selection by the indices can be evaluated by bootstrapping. I illustrate the usage of the indices and the approximate significance test with both empirical and simulated sequences. The tests show that distance matrices from protein gel electrophoresis and from genome rearrangement events do not violate the molecular clock hypothesis, and that the evolution of the third codon position conforms to the molecular clock hypothesis better than the second codon position in vertebrate mitochondrial genes. I outlined evolutionary distances that are appropriate for phylogenetic reconstruction and dating.     

A Modified “Best Maximum Likelihood” Estimator of Line Regression with Errors in Both Variables: An Application for Estimating Genetic Admixture

The problem of estimation when both variables are subject to error in a linear regression model has been discussed in the literature and it has wide applications in econometrics and other social sciences. In this paper we consider the relaxation of the assumption of homoscedasticity and introduce the covariance structure of errors of measurements in the analysis to obtain a Modified Best Maximum Likelihood (MBML) estimator of the regression coefficient. We also provide an application of the above modification to estimate the extent of genetic contribution of a parental population in an admixed population. With data on frequencies of “unique” African and Caucasian alleles in US Blacks, it is shown that US Blacks have 30.9·2.2 percent genes that are of Caucasian origin.