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At least 199 records · Page 11Linked to original sources
PubMed2004

Polygenic variation maintained by balancing selection: pleiotropy, sex-dependent allelic effects and G x E interactions.

We investigate three alternative selection-based scenarios proposed to maintain polygenic variation: pleiotropic balancing selection, G x E interactions (with spatial or temporal variation in allelic effects), and sex-dependent allelic effects. Each analysis assumes an additive polygenic trait with n diallelic loci under stabilizing selection. We allow loci to have different effects and consider equilibria at which the population mean departs from the stabilizing-selection optimum. Under weak selection, each model produces essentially identical, approximate allele-frequency dynamics. Variation is maintained under pleiotropic balancing selection only at loci for which the strength of balancing selection exceeds the effective strength of stabilizing selection. In addition, for all models, polymorphism requires that the population mean be close enough to the optimum that directional selection does not overwhelm balancing selection. This balance allows many simultaneously stable equilibria, and we explore their properties numerically. Both spatial and temporal G x E can maintain variation at loci for which the coefficient of variation (across environments) of the effect of a substitution exceeds a critical value greater than one. The critical value depends on the correlation between substitution effects at different loci. For large positive correlations (e.g., rho(ij)2>3/4), even extreme fluctuations in allelic effects cannot maintain variation. Surprisingly, this constraint on correlations implies that sex-dependent allelic effects cannot maintain polygenic variation. We present numerical results that support our analytical approximations and discuss our results in connection to relevant data and alternative variance-maintaining mechanisms.

Data Interpretation, Statistical↗
PubMed1990

[The diagnosable rate of beta-thalassemia in Chinese population and the strategy for selecting genetic markers in prenatal diagnosis of the disease].

It is possible to use some beta-thalassemia gene linkage markers for prenatal diagnosis of the disease currently. But there are some limitations due to incomplete linkage between these genetic markers and beta-thalassemia gene in population. The diagnosable rate of the genetic markers and their combinations have been calculated according to the polymorphism distribution data of the seven genetic markers in Chinese population. Then according to the diagnosable rate of each genetic marker and their combinations, the following is deduced: (1) Precedent estimation to the diagnosable rate of prenatal diagnosis; (2) Select the optimum strategy for prenatal diagnosis of beta-thalassemia suitable for Chinese population. In this paper, an optimum line is presented, regarding to select genetic markers for prenatal diagnosis of beta-thalassemia in Chinese population. Meanwhile, the method of gene linkage analysis and that of using oligonucleotide probe are compared.

Asian People↗
PubMed2005

Pharmacokinetic characteristics of amiodarone in long-term oral therapy in Japanese population.

To evaluate the pharmacokinetic properties and an optimum dose schedule of amiodarone in long-term oral therapy, serum concentrations of amiodarone and its metabolite, desethylamiodarone, were monitored from 345 Japanese inpatients who received amiodarone therapy for a variety of cardiac arrhythmias. Serum amiodarone and desethylamiodarone concentrations were determined by high performance liquid chromatography system. It was observed that the amiodarone and desethylamiodarone concentrations gradually increased with time. The frequency distribution in the amiodarone clearance of 245 subjects, who received fixed maintenance amiodarone therapy for at least 6 months, was nearly a unimodal one. The variation in the ratio of desetylamiodarone to amiodarone concentration in serum was very small. Although no differences in age, dose, dose duration, amiodarone or desethyamiodarone concentration or ratio were observed between men and women: however, the mean amiodarone clearance of women was significantly higer than that of men. The laboratory data were mostly within normal values and no significant relations were observed between serum amiodarone concentration and clinical laboratory data. These results suggest that the individual variation in pharmacokinetics of amiodarone is comparatively small, which might be sufficient to decide that the maintenance dose was the same one (200 mg/d) in long-term oral amiodarone therapy.

Administration, Oral↗
PubMed1994

Obtaining birth and mortality patterns from structured population trajectories.

"A method is presented for unravelling the demographic equation for structured populations. A solution to the McKendrick-von Foerster equation is constructed using spline functions and this is fitted to stage-structured population data in such a way that the solution is smooth, positive, and does not imply negative death rates. The smoothness of the surface, and hence the complexity of the population model, is determined in a statistically optimum manner using cross validation. Time- and age-dependent death rates can be obtained as well as time-dependent birth rates. Confidence intervals are obtained for population size and death rates that give a 95% probability that the true population dynamics are within the intervals. Practical application of the method is demonstrated, and comparison made with three alternative methods."

Demography↗
PubMed1977

Nutritional needs of special populations at risk.

The nutritional needs of special populations at risk require a concerned government, a concerned bureaucracy which funds and operates health, welfare and food delivery systems. Equally, if not even more important, is the concern and involvement of citizens at the "local-state-county-city" level. Some of the vulnerable groups, such as the migrant workers and the Native Americans, are the responsibiliity of the Federal Government. This does not mean that State and local citizens should do nothing, which by and large characterizes what has happened. The solution to provide optimum nutrition for the entire U.S. population is not merely a recitation of: food production figures, food costs, documentation of how much the Government spends on feeding people, how many free or reduced school lunches are served, how good or bad the problem is. We need to update and monitor programs that deal with the delivery of health, welfare and food; nutrition education for educators, Congress, doctors, and the public; food enrichment and fortification; nutrient analysis of foods; and nutrition research.

Adolescent↗
PubMed2005

Drift and scaling in estimation of distribution algorithms.

This paper considers a phenomenon in Estimation of Distribution Algorithms (EDA) analogous to drift in population genetic dynamics. Finite population sampling in selection results in fluctuations which get reinforced when the probability model is updated. As a consequence, any probability model which can generate only a single set of values with probability 1 can be an attractive fixed point of the algorithm. To avoid this, parameters of the algorithm must scale with the system size in strongly problem-dependent ways, or the algorithm must be modified. This phenomenon is shown to hold for general EDAs as a consequence of the lack of ergodicity and irreducibility of the Markov chain on the state of probability models. It is illustrated in the case of UMDA, in which it is shown that the global optimum is only found if the population size is sufficiently large. For the needle-in-a haystack problem, the population size must scale as the square-root of the size of the search space. For the one-max problem, the population size must scale as the square-root of the problem size.

Algorithms↗
PubMed1996

[Hereditary biochemical diversity in the processes of evolution and individual development].

Results of long-term studies of Russian authors on regularities of expression of hereditary biochemical diversity in evolution and development are reviewed. Primary attention is given to the concepts of genetic monomorphism and genetic stability of population systems, principles of adaptive gene pool structure and optimum genetic diversity, historical and conservation genetics, the concept of the multilevel gene expression, and temporal regulation of ontogenetic functioning of gene clusters coding for enzymes. A universal genetic approach to the problems of evolution and ontogeny is proposed. A population is regarded as a superorganism whose key property is the hierarchic structure of its genetic stability from the stability of monomorphic genes via stability of polymorphic gene frequencies in a multilevel population system to the stability of the total amount of gene diversity in this system. A multicellular organism is also regarded as a developing hierarchical system of populations of cells and genes interacting in a nonrandom fashion. This maintains stability of metabolic processes and is expressed in consistent correlations between monogenic and polygenic morphophysiological characters. Properties of both organisms are determined by the adaptive heterozygosity optimum, the disturbance of which has negative consequences for both individuals and populations. On the basis of these results and the concept on the common nature of evolutionary and ontogenetic processes, the following conclusions are drawn: genetic processes can be either favorable or adverse for developing organisms and populations; the state of genetic processes can be determined by analysis of gene diversity and their deviations from the optimum, taking into account the adaptive gene pool structure; and negative hazardous consequences of extreme external effects at both the individual and population levels can be detected by methods of biochemical genetics in specially planned monitoring programs. Knowledge of normal processes of realization of hereditary information in evolution of populations and in ontogeny opens up new perspectives in detection of unfavorable processes and their correction. This approach proved promising both for preventive and clinical medicine and for exploitation and artificial reproduction of biological resources.

Adaptation, Physiological↗
PubMed1992

Measurement of 3-D facial contours for the design of half-face respirators.

A portable anthropometric test rig capable of obtaining three-dimensional face shape data was developed and used to obtain information relating to facial shape, stiffness, and variance for a selected subgroup of respirator users in the Australian work force. A respirator seal shape most suited to the sample population was obtained by studying the central portion of the face of all the subjects. The optimum seal shape was established by following the path of minimum variance among all the faces; the method provided information on the shape, dimensions, and stiffness of the optimum seal for a respirator suited to the sample population. The seal surface flexibility required for a comfortable fit was determined by measuring the deflection of the skin caused by an applied pressure and using this information along with face shape variance data. Results indicated that the required flexibility in the seal surface increased toward the lower portion of the face.

Anthropometry↗
PubMed2006

Stochasticity, complex spatial structure, and the feasibility of the shifting balance theory.

Sewall Wright's shifting balance theory of evolution posits a mechanism by which a structured population may escape local fitness optima and find a global optimum. We examine a one-locus, two-allele model of underdominance in populations with differing spatial arrangements of demes, both analytically and with Monte Carlo simulations. We find that inclusion of variance in interpatch connectivities can significantly reduce the number of generations required for fixation of the more favorable allele relative to island and stepping-stone models. Although time to fixation increases with migration rate in all cases, the presence of one or two relatively isolated demes may reduce the number of generations by 80% or more. These results suggest that the shifting balance process may operate under less restrictive conditions than those found with a simple spatial arrangement of demes.

Biological Evolution↗
PubMed1981

Optimal birthweights in Peruvian populations at high and low altitudes.

This study tests the hypothesis that optimum birthweight for survival is lower among hospital-born infants in Puno, Peru (altitude 3860 m) than that among their counterparts at low altitude in Tacna, Peru (altitude 600 m). The data are derived from hospital birth records for 1971 and 1972 and municipal death records for 1971 through 1973. Linking these records permits analysis of the patterns of mortality in relation to birthweight. Stabilizing selection upon birthweight is operating in both populations. The high altitude population has a lower mean birthweight and a lower optimal birthweight. The Puno population is closer to its optimal birthweight distribution and, as a result of mortality during infancy, is approaching its optimum birthweight distribution for survival more rapidly than the Tacna population. It appears that the high altitude Puno population may well be adapted to its environment in the sense that there is less selective mortality on birthweight phenotypes.

Altitude↗
PubMed2000

Metastable evolutionary dynamics: crossing fitness barriers or escaping via neutral paths?

We analytically study the dynamics of evolving populations that exhibit metastability on the level of phenotype or fitness. In constant selective environments, such metastable behavior is caused by two qualitatively different mechanisms. On the one hand, populations may become pinned at a local fitness optimum, being separated from higher-fitness genotypes by a fitness barrier of low-fitness genotypes. On the other hand, the population may only be metastable on the level of phenotype or fitness while, at the same time, diffusing over neutral networks of selectively neutral genotypes. Metastability occurs in this case because the population is separated from higher-fitness genotypes by an entropy barrier: the population must explore large portions of these neutral networks before it discovers a rare connection to fitter phenotypes. We derive analytical expressions for the barrier crossing times in both the fitness barrier and entropy barrier regime. In contrast with 'landscape' evolutionary models, we show that the waiting times to reach higher fitness depend strongly on the width of a fitness barrier and much less on its height. The analysis further shows that crossing entropy barriers is faster by orders of magnitude than fitness barrier crossing. Thus, when populations are trapped in a metastable phenotypic state, they are most likely to escape by crossing an entropy barrier, along a neutral path in genotype space. If no such escape route along a neutral path exists, a population is most likely to cross a fitness barrier where the barrier is narrowest, rather than where the barrier is shallowest.

Biological Evolution↗
PubMed1981

Biochemical properties of duplicated isozymes of phosphoglucose isomerase in the plant Clarkia xantiana.

The structural gene locus specifying subunits of cytoplasmic isoenzymes of phosphoglucose isomerase (PGI) is present in duplicate in many diploid species of Clarkia (Onagraceae), a genus of annual plants native to California. We studied the kinetic properties and molecular weights of a large number of genetically defined and highly purified PGIs in C. xantiana, a number of species with the duplication, as a means of examining the biochemical consequences of the evolution of a new gene locus. This species is primarily outcrossing, but also includes several previously described predominantly self-pollinating populations. Both cytoplasmic PGI loci in the outcrossing populations are polymorphic and their enzyme products are readily separated by electrophoresis. The PGIs from the outcrossing populations were rated by electrophoresis. The PGIs from the outcrossing populations were generally closely similar in molecular weight, pH optimum, heat sensitivity, energy activation, and apparent Km (fructose-6-phosphate). The PGI loci in the selfing populations are monomorphic and specify enzymes having identical electrophoretic mobilities to those coded by the most frequent alleles of the outcrosser. The PGI isozymes in the selfers differed fivefold in Km, suggesting that they have a very different catalytic effectiveness. The high Km of the PGI-3A' isozyme (1.1mM) was anomalous among the PGIs examined and would likely be disadvantageous in a species which lacked other more normally functioning PGIs. But in the cytoplasm of the selfing plants, it is present with other PGIs that have low Km values. The PGI-3A' enzyme is a good candidate for a gene product coded by a "forbidden" mutation that could not have been established in the absence of the duplication. The rationale for this suggestion is described and it is also pointed out that the divergence of duplicated genes is influenced by many factors such as the breeding system and other population factors as well as the effect of particular mutations.

Catalysis↗
PubMed1988

Preliminary characterization of the multiple forms of ram sperm hyaluronidase.

An investigation was made of the inter-relationships and characteristics of various hyaluronidase forms isolated from ram spermatozoa. They were shown to be members of an oligomeric series, apparently formed by intermolecular disulphide cross-linking. Two monomer species were detected, alpha (Mr 89,600) and beta (Mr 81,200). Although the alpha species predominated, the two were evenly distributed throughout the oligomer population, and they shared antigenic determinants; the beta species did not arise from the alpha species as a result of catabolism following cell disruption. The oligomeric series was of the form [Hyal]n, where n = 1, 2, 4, 5, 6, 7 etc.; no trimer was detectable. Though essentially cationic, part of the hyaluronidase population also had anionic characteristics, probably due to oxidation of free thiol groups. In the anionic subpopulation tetramers and higher oligomers predominated, whereas the non-anionic subpopulation was composed of monomers, dimers and tetramers. The pH optimum of the monomer was 4.3 in 0.2 M-NaCl/0.1 M-sodium citrate, whereas that of the anionic oligomers was 4.9. Both serum albumin and polylysine stimulated enzyme activity at pH 4.0 in the absence of NaCl; polylysine was particularly effective. NaCl diminished the stimulatory effects, and essentially suppressed them above the pH optimum. The specific activities of different oligomer populations were the same as that of the monomer, and conversion of oligomers into monomer by reduction had likewise no effect upon the specific activity. Low concentrations of poly(vinyl alcohol), poly(ethylene glycol) or polyvinylpyrrolidone stabilized soluble hyaluronidase activity by preventing the enzyme's binding to surfaces; solutions of anionic oligomers were further stabilized by NaCl. Enzyme preparations were stable for several months frozen in the presence of poly(vinyl alcohol) and salt.

Animals↗
PubMed1984

Recent applied field research activities carried out in tropical Africa.

A review has been undertaken of applied field research in malaria in tropical Africa from 1975 onwards, the aim being to show recent trends and to emphasize the needs for further research in support of malaria control.Studies are grouped according to whether they relate to parasites, vectors, epidemiology, or control. The first group is concerned mainly with the study of the appearance and development of resistance of Plasmodium falciparum to drugs. The second group deals with vector bionomics and the differentiation of various species in the Anopheles gambiae complex. Next come descriptive and analytical surveys and studies on the characterization of malaria as a health and social problem, the importance of some congenital factors, and immunological aspects of the disease. Studies on control comprise the use of drugs, insecticides, and biological methods.The main achievements of research to date have been to improve knowledge of the distribution of chloroquine resistance, which is still mainly confined to East Africa; to clarify the distribution of the components of the A. gambiae complex, even in the formerly known A. gambiae sensu stricto; and to provide indications that the use of mass chemosuppression may favour drug resistance and reduce the malaria antibodies in the population, although the clinical significance of the latter needs to be elucidated.Among the domains considered important for future research are the monitoring of drug sensitivity, not only to 4-aminoquinolines but also to alternative drugs; the determination of optimum drug regimens in various circumstances and population groups; studies on malaria mortality, morbidity, and immunity as related to the use of drugs; the study of the epidemiological importance of various vector species, their behaviour and amenability to control; and feasibility studies on various methods of control in the context of the primary health care settings, including cost-effectiveness and cost-benefit determination.

Africa↗
PubMed2000

The evolution of sexual size dimorphism in the house finch. II. Population divergence in relation to local selection.

Recent colonization of ecologically distinct areas in North America by the house finch (Carpodacus mexicanus) was accompanied by strong population divergence in sexual size dimorphism. Here we examined whether this divergence was produced by population differences in local selection pressures acting on each sex. In a long-term study of recently established populations in Alabama, Michigan, and Montana, we examined three selection episodes for each sex: selection for pairing success, overwinter survival, and within-season fecundity. Populations varied in intensity of these selection episodes, the contribution of each episode to the net selection, and in the targets of selection. Direction and intensity of selection strongly differed between sexes, and different selection episodes often favored opposite changes in morphological traits. In each population, current net selection for sexual dimorphism was highly concordant with observed sexual dimorphism--in each population, selection for dimorphism was the strongest on the most dimorphic traits. Strong directional selection on sexually dimorphic traits, and similar intensities of selection in both sexes, suggest that in each of the recently established populations, both males and females are far from their local fitness optimum, and that sexual dimorphism has arisen from adaptive responses in both sexes. Population differences in patterns of selection on dimorphism, combined with both low levels of ontogenetic integration in heritable sexually dimorphic traits and sexual dimorphism in growth patterns, may account for the close correspondence between dimorphism in selection and observed dimorphism in morphology across house finch populations.

Alabama↗
PubMed1977

Growth characteristics of populations of Tibetan origin in Nepal.

Previous growth studies of highland-dwelling populations in the ecologically diverse areas of Peru and Ethiopia have yielded highly varied results: the retarded growth of the Peruvian sample was attributed to the effects of hypoxia, while the increased height and weight of the highland Ethiopian sample could be traced to better health conditions in the highland village than in the lowland village studied. In an attempt to provide a basis for evaluating studies of growth at high altitude, the present study compared Sherpa children living in the Everest region of Nepal with Tibetan children living in Kathmandu. It was found that: (1) the growth of Sherpa and Tibetan children is considerably retarded compared to other high altitude populations; (2) despite conditions favorable for optimum growth among the Tibetans, their growth resembled that of the Sherpas and (3) increased chest circumference, which seems to reflect a developmental acclimatization to hypoxia among Peruvian high-altitude natives, was not seen among the Sherpas.

Adolescent↗
PubMed2002

Optimal designs of two-stage studies for estimation of sensitivity, specificity and positive predictive value.

The cost efficiency of estimation of sensitivity, specificity and positive predictive value from two-stage sampling designs is considered, assuming a relatively cheap test classifies first-stage subjects into several categories and an expensive gold standard is applied at stage two. Simple variance formulae are derived and used to find optimal designs for a given cost ratio. The utility of two-stage designs is measured by the reduction in variances compared with one-stage simple random designs. Separate second-stage design is also compared with proportional allocation (PA). The maximum percentage reductions in variance from two-stage designs for sensitivity, specificity and positive predictive value estimation are P per cent, (1-P) per cent and W, respectively, where P is the population prevalence of disease and W the population percentage of test negatives. The optimum allocation of stage-two resources is not obvious: the optimum proportion of true cases at stage two may even be less than under PA. PA is near optimal for sensitivity estimation in most cases when prevalence is low, but inefficient compared with the optimal scheme for specificity.

Asthma↗
PubMed1984

Performance of Bos taurus X zebu crossbreds under village conditions.

Data on first lactation performance of 751 Holstein X zebu and Jersey X zebu crossbred heifers of various grades were collected under rural field conditions in Maharashtra. The heifers were the progeny of seven Danish Holstein (Sortbroget Dansk Malkekvoeg) sires, 33 homebred Holstein sires, six Danish Jersey sires and 35 homebred Jersey sires. The least-squares analysis showed that the location and genetic group within the two classes of crossbreds significantly affected the milk yield. In pooled data the 7/8 Holstein crossbreds produced by homebred sires were significantly superior to other genetic groups of either Holstein or Jersey inheritance. The milk yield increased with increasing level of homebred Holstein inheritance and with Jersey inheritance. Danish Holstein sires were the best to produce the halfbred Holstein crosses. The differences in the genetic groups accounted for 20% of the phenotypic variance in 305-day milk yield and for 2% of the variance of the lactation length in the crossbred population. It is inferred that the optimum level of exotic breed inheritance in Maharashtra would be above 50% and that the genetic group of the dams needs to be considered when evaluating the performance of a sire's progeny.

Animals↗