Population genetic structure of variable drug response.

Geographic patterns of genetic variation, including variation at drug metabolizing enzyme (DME) loci and drug targets, indicate that geographic structuring of inter-individual variation in drug response may occur frequently. This raises two questions: how to represent human population genetic structure in the evaluation of drug safety and efficacy, and how to relate this structure to drug response. We address these by (i) inferring the genetic structure present in a heterogeneous sample and (ii) comparing the distribution of DME variants across the inferred genetic clusters of individuals. We find that commonly used ethnic labels are both insufficient and inaccurate representations of the inferred genetic clusters, and that drug-metabolizing profiles, defined by the distribution of DME variants, differ significantly among the clusters. We note, however, that the complexity of human demographic history means that there is no obvious natural clustering scheme, nor an obvious appropriate degree of resolution. Our comparison of drug-metabolizing profiles across the inferred clusters establishes a framework for assessing the appropriate level of resolution in relating genetic structure to drug response.     

Correction of the anomalous electrophoretic behavior of ribonuclease A

Summary Ribonuclease A behaves anomalously on polyacrylamide gel electrophoresis at acid pH. The distance traveled by the protein is a function of the amount of enzyme added at the lower range of detectable activity (10 pg to 100 ng). Addition of myoglobin (1 mg/ml) abolishes the anomaly. The observations are consistent with the known affinity of RNase for anions. Caution is warranted in the interpretation of apparent electrophoretic variants of RNase observed at low concentrations of enzyme.Acknowledgment. This is publication No. 80-33 from the Department of Medical Genetics and was supported in part by the Indiana University Human Genetics Center, PHS GM 21054.     

Comparative kinetics of greening in etiolated intact and excized wheat leaves

Summary Differential characteristics of lag phase of chlorophyll accumulation during greening of etiolated intact and excized wheat leaves are discussed. Relatively, a prolonged lag phase in case of excized leaves is attributed to the lack of proper hormonal level in the leaves after excision.Acknowledgment. We thank Prof. M. C. Dash for encouragement and facilities. The assistance of Mr A. N. Misra is acknowledged.