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At least 451 records · Page 25Linked to original sources
PubMed1999

Quantitative genetics of floral traits in a gynodioecious wild strawberry Fragaria virginiana: implications for the independent evolution of female and hermaphrodite floral phenotypes.

The independent evolution of floral phenotype is an important part of the process of gender specialization during the evolution of dioecy from hermaphroditism. However, we have little information on the genetic variation of floral traits in species with separate genders. Gynodioecious species (co-occurrence of females and hermaphrodites) have a breeding system intermediate between hermaphroditism and complete separation of the sexes (dioecy) and thus can provide insight into the genetic architecture underlying floral phenotype with respect to both primary (stamens and carpels) and secondary (petals) sexual traits. I used a nested breeding design to examine the potential for response to selection on floral traits and to examine whether this response would be similar in the two sex morphs of gynodioecious Fragaria virginiana. There was significant genetic variation underlying all floral traits, although narrow-sense heritabilities (ranging from -0.25 to 0.44) were, in most cases, much lower than broad-sense ones (ranging from 0.28 to 1. 53). Moreover, the sex morphs differed significantly in their heritabilities for shared traits, such as stamen length, and showed a tendency towards differing significantly in others, like carpel number and petal length. In addition, correlations between the sex morphs for these traits (ranging from 0.41 to 0.58) were significantly greater than 0, but less than 1. These results indicate that greater sexual dimorphism could evolve in this population of F. virginiana, even if selection on these traits is not divergent. However, strong developmental integration of floral traits (e.g. stamen length and petal length) and high levels of nonadditive genetic variance may represent barriers to the evolution of complete sexual dimorphism.

Biological Evolution↗
PubMed2000

Evidence of a substantial genetic basis for risk of adult periodontitis.

BACKGROUND: A few previous studies have suggested that risk for adult periodontitis (AP) has a genetic (heritable) component. We estimated genetic and environmental variances and heritability for gingivitis and adult periodontitis using data from twins reared together. METHODS: One hundred seventeen (117) pairs of adult twins (64 monozygotic [MZ] and 53 dizygotic [DZ] pairs) were recruited. Probing depth (PD), attachment loss (AL), plaque, and gingivitis (GI) were assessed on all teeth by two examiners. Measurements were averaged over all sites, teeth, and examiners. Extent of disease in subjects was defined at four thresholds: the percentage of teeth with AL > or = 2, AL > or = 3, PD > or = 4, or PD > or = 5 mm. Genetic and environmental variances and heritability were estimated using path models with maximum likelihood estimation techniques. RESULTS: MZ twins were more similar than DZ twins for all clinical measures. Statistically significant genetic variance was found for both the severity and extent of disease. AP was estimated to have approximately 50% heritability, which was unaltered following adjustments for behavioral variables including smoking. In contrast, while MZ twins were also more similar than DZ twins for gingivitis scores, there was no evidence of heritability for gingivitis after behavioral covariates such as utilization of dental care and smoking were incorporated into the analyses. CONCLUSIONS: These results confirm previous studies and indicate that approximately half of the variance in disease in the population is attributed to genetic variance. The basis for the heritability of periodontitis appears to be biological and not behavioral in nature.

Adult↗
PubMed2001

Sieve analysis: methods for assessing from vaccine trial data how vaccine efficacy varies with genotypic and phenotypic pathogen variation.

A key component in the evaluation of efficacy of a vaccine to protect against disease caused by an antigenically diverse infectious pathogen in a preventative vaccine trial is assessing how vaccine-induced protection depends on genotypic and phenotypic variations of the exposing pathogen. This assessment is made by comparing pathogen isolates between infected vaccinated subjects and infected unvaccinated subjects. A survey of efficacy trial reports reveals a lack of systematic, quantitative investigation in this question. Analysis tools for testing if vaccine protection against disease is superior against some pathogen strains, and for estimating the magnitude of this differential vaccine protection, are described. The broad applicability of the methods is illustrated through analysis of isolates taken from persons infected while participating in vaccine trails for cholera, HIV-1, hepatitis B, rotavirus, and pneumococcus. These analyses reveal intriguing trends for Genentech's monovalent rgp120 HIV-1 vaccine, for two whole-killed-cell oral cholera vaccines, and for other vaccines.

Cholera↗
PubMed1984

Enzyme variation in Trypanosoma brucei spp. I. Evidence for the sub-speciation of Trypanosoma brucei gambiense.

Three groups of stocks of Trypanosoma brucei ssp, defined by the criteria of host, human serum resistance and place of isolation as T. b. gambiense, T. b. brucei (Nigeria) and T. b. brucei/rhodesiense (non-gambiense, Uganda) were screened for electrophoretic variation at 20 enzyme loci. One enzyme (Peptidase C) was found to differentiate all T. b. gambiense stocks from the other T. brucei stocks and, taken together with specific variants of 5 other enzymes, could be used to unambiguously define T. b. gambiense stocks. Using a population genetics approach, the frequencies of the different variants in the three groups of stocks were estimated and from them the average similarity and difference between groups were measured using the statistics of genetic identity (I) and genetic distance (D). These results show firstly, that T. b. gambiense is more different from the other two groups than they are from each other and, secondly, that the values of I and D obtained are consistent with T. b. gambiense constituting a sub- or sibling species of T. brucei. Three domestic animal isolates from Zaire and Cameroun were also screened for enzyme variation and two of these identified as T. b. gambiense, thereby establishing the existence of an animal reservoir host. In parallel, these stocks were tested for human serum resistance resulting in the same identification. Studies of the antigen repertoires and antigen gene structure were carried out by other workers on all the T. b. gambiense stocks reported here and the same conclusions reached as to the identification and ability to discriminate this subspecies from other groups of T. brucei stocks. The results presented here are discussed in relation to other published data on enzyme variation in T. brucei.

Alleles↗
PubMed1999

Molecular population genetics of the primary neotropical malaria vector Anopheles darlingi using mtDNA.

Samples of the neotropical malaria vector Anopheles darlingi from Bolivia, Brazil, and Venezuela were analyzed to test for differences in mitochondrial haplotype frequencies. With the use of molecular variance components and F-statistics, significant genetic variability of An. darlingi was found apportioned primarily among populations within regions or within populations, with regions defined either as biomes (n = 5) or ecoregions (n = 2). The Mantel analysis resulted in a significant correlation [Prob (r) = 0.009] between genetic and geographic distances, evidence that these populations are genetically isolated by distance. Such isolation could reflect differences in phenotypes for factors affecting vector capacity.

Animals↗
PubMed1986

Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins.

A statistical analysis of the radiosensitivity of 204 different survival curves of nontransformed human fibroblast cell strains of different genetic origins was made using three criteria: the multi-target one-hit model (characterized by parameters n and D0), the surviving fraction for a 2 Gy dose (S2) and the mean inactivation dose (D). D is found to be the best parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and for discrimination between groups of cell strains of differing radiosensitivity. Its use allows the description of a range of 'normal' radiosensitivity for control fibroblasts and the classification of the various genetic disorders as a function of their mean radiosensitivity expressed in terms of D. Nine groups of cell strains appear to exhibit radiosensitivity which differs significantly from that of the controls: seven groups are hypersensitive (ataxia-telangiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and from individuals with chromosome 13 anomalies). Since the coupled parameter n and D0 failed to discriminate between the radiosensitivity of the different genetic groups, we recommend the use of D to make an intercomparison of intrinsic radiosensitivity of nontransformed human fibroblasts.

Cell Line↗
PubMed2004

The heritability of breast cancer: a Bayesian correlated frailty model applied to Swedish twins data.

The aim of this study was to investigate the role of genes and environment in susceptibility to breast cancer and to give an estimate of heritability in the propensity to develop the disease. To do this we applied an interdisciplinary approach, merging models developed in the field of demography and survival analysis - so-called frailty models - and models coming from quantitative genetics and epidemiology, namely genetic models. In our study, the inferential problem was solved in a Bayesian framework and the numerical work was carried out using MCMC methods. We used the special information coming from twin data, particularly breast cancer data, from the Swedish Twin Register. The application of a correlated log-normal frailty model leads to a very large estimate of the population heterogeneity (sigma = 6.7), and relatively small correlations between co-twins' frailties - around 0.3 for monozygotic and 0.1 for dizygotic twins. Comparing three different genetic models (an ACE, an AE and an ADE model), we furthermore concluded that genetic effects would explain globally almost 30% of the total variability of propensity to breast cancer. Environmental effects would be predominant in determining breast cancer susceptibility and these effects would be primarily individual-specific, that is, non-shared effects. Finally, a model which includes dominance genetic effects (ADE model) is preferred for genetic and statistical reasons.

Bayes Theorem↗
PubMed2005

A note on generalized Genome Scan Meta-Analysis statistics.

BACKGROUND: Wise et al. introduced a rank-based statistical technique for meta-analysis of genome scans, the Genome Scan Meta-Analysis (GSMA) method. Levinson et al. recently described two generalizations of the GSMA statistic: (i) a weighted version of the GSMA statistic, so that different studies could be ascribed different weights for analysis; and (ii) an order statistic approach, reflecting the fact that a GSMA statistic can be computed for each chromosomal region or bin width across the various genome scan studies. RESULTS: We provide an Edgeworth approximation to the null distribution of the weighted GSMA statistic, and, we examine the limiting distribution of the GSMA statistics under the order statistic formulation, and quantify the relevance of the pairwise correlations of the GSMA statistics across different bins on this limiting distribution. We also remark on aggregate criteria and multiple testing for determining significance of GSMA results. CONCLUSION: Theoretical considerations detailed herein can lead to clarification and simplification of testing criteria for generalizations of the GSMA statistic.

Chromosome Mapping↗
PubMed1982

Genetic variance of blood pressure levels in infant twins.

A cohort of 166 twin pairs (67 monozygotic and 99 dizygotic) born at the Jackson Memorial Hospital/University of Miami Medical Center between July 1, 1976 and December 31, 1980, was followed from birth to one year of age in order to estimate the genetic variance of blood pressure during the first year of life. The sex-adjusted summary estimate of heritability for systolic blood pressure during all of infancy was 0.22 (p less than 0.001), but statistically significant genetic variance was not found for diastolic blood pressure. When using blood pressures from six to 12 months of age, adjusted for infant sex, heritability was estimated as 0.33 (p less than 0.001) for systolic blood pressure and 0.24 (p = 0.04) for diastolic blood pressure; adjustment for body weight reduced these estimates to 0.27 (p less than 0.001) and 0.17 (p = 0.13), respectively.

Blood Pressure↗
PubMed2006

Possible association between response inhibition and a variant in the brain-expressed tryptophan hydroxylase-2 gene.

UNLABELLED: The ability to inhibit a response is an important component of normal behavioral control and is an aspect of psychopathology when diminished. Converging evidence implicates the serotonergic neurotransmitter system in response inhibition circuitry. OBJECTIVES: The present study examined potential associations between serotonergic genetic markers and response inhibition as indexed by Stop Task performance. METHODS: College-age participants (N=199) completed self-report questionnaires, the computerized Stop Task, and donated buccal cells for genetic analyses. Statistics were analyzed by ANOVA. RESULTS: Stop Signal reaction time was not associated with allelic variation at a monoamine oxidase A promoter length polymorphism or a serotonin 1B terminal autoreceptor polymorphism (G861C). An intronic genetic marker of the neuronal tryptophan hydroxylase-2 (the rate-limiting enzyme for serotonin biosynthesis) gene, however, was associated with the Stop Signal reaction time. Individuals homozygous for the T variant at an intron-8 polymorphism had the longest Stop Signal reaction time (i.e. greater impulsivity, P=0.01), and this effect was stronger in males (P=0.01) than in females (P=0.10). CONCLUSIONS: A genotype at an intron-8 tryptophan hydroxylase-2 polymorphism was associated with response inhibition as indexed by the Stop Task. These results, if replicated, would implicate dorsal raphe serotonin neurons in response inhibition. It may be that individuals with the T/T genotype may have reduced tryptophan hydroxylase-2 function and correspondingly lower central serotonin levels; however, further investigation of the reported association is required.

Adult↗
PubMed1994

Genetic analysis of a complex disease.

A complex disease may be defined as a disease that has a complex phenotype, no single causal agent and a range of influencing factors, both genetic and environment. The paper considers how the aetiology of such disorders may be unravelled using recently developed genetical and statistical methods. Problems are illustrated using ischaemic heart disease, congenital neural tube defects and depression as examples.

Coronary Disease↗
PubMed1990

Estimation of individual genetic and environmental factor scores.

Implicit in the application of the common-factor model as a method for decomposing trait covariance into a genetic and environmental part is the use of factor scores. In multivariate analyses, it is possible to estimate these factor scores for the communal part of the model. Estimation of scores on latent factors in terms of individual observations within the context of a twin/family study amounts to estimation of individual genetic and environmental scores. Such estimates may be of both theoretical and practical interest and may be provided with confidence intervals around the individual estimates. The method is first illustrated with stimulated twin data and next is applied to blood pressure data obtained in a Dutch sample of 59 male adolescent twin pairs. Subjects with high blood pressure can be distinguished into groups with high genetic or high environmental scores.

Adolescent↗
PubMed1996

[Genetic differentiation of helminths on the basis of data of polymerase chain reaction using random primers].

The genetic variability of helminths belonging to the three classes Cestoda, Nematoda and Trematoda was analysed by means of polymerase chain reaction with randomly amplified polymorphic DNA (RAPD-PCR). Dendrograms of genetic relationships between some representatives of the genus Trichinella, Fasciola hepatica, Cysticerus ovis, Echinococcus granulosus, and Nematodirus spathiger were constructed on the basis of DNA amplification patterns. The formation of ecological and genetic adaptations in the helminth groups studied is discussed.

Adaptation, Physiological↗
PubMed1988

Angular homeostasis. V: Some issues in genetics, ontogeny, and evolution.

We discuss a provisional model that deals with aspects of normal control of the direction in which cells grow; hence, the organization of structure. The interacting issues of genetics, ontogeny, and phylogeny in relationship to normal development and its defects are addressed. Our main goal is to define a model with a small and sufficient set of conditions that would make it possible to undertake statistically efficient genetic studies of certain congenital defects. But to do so in plausible and heuristic terms, one must address two classical questions: 1) How is the genome translated (or sometimes mistranslated) into a phenotype that is clinically conspicuous and that can be the object of genetic selection, and hence of evolution? 2) Granted that evolution of species occurs in small, rare steps, what is the path that calls for the smallest number of mutations through which ontogenesis could have developed, the intermediate stages being conserved because of actual phenotypic advantage?

Cell Division↗
PubMed2005

InterferenceAnalyzer: tools for the analysis and simulation of multi-locus genetic data.

BACKGROUND: Good statistical models for analyzing and simulating multilocus recombination data exist but are not accessible to many biologists because their use requires reasonably sophisticated mathematical and computational implementation. While some labs have direct access to statisticians or programmers competent to carry out such analyses, many labs do not. We have created a platform independent application with an easy-to-use graphical user interface that will carry out such analyses including the simulations needed to bootstrap confidence intervals for the parameters of interest. This software should make multi-locus techniques accessible to labs that previously relied on less powerful and potentially statistically confounded single interval or double interval techniques. RESULTS: We introduce InterferenceAnalyzer, an implementation with a user-friendly graphical interface incorporating previously developed algorithms for the analysis and simulation of multilocus recombination data. We demonstrate the use and features of the program with an example of multilocus tetrad data from the mustard plant, Arabidopsis thaliana, and the yeast, Saccharomyces cerevisiae. CONCLUSION: InterferenceAnalyzer provides easy access to the powerful and appropriate statistical tools for the multi-locus analysis of genetic data.

Algorithms↗
PubMed2004

Case-control association studies with matching and genomic controlling.

Family-based association studies have gained in popularity for mapping disease-susceptibility gene(s) of complex diseases. However, recruiting family controls is often more difficult than recruiting unrelated controls. The author proposes a case-control study, where the possible biases due to population stratification are controlled by matching in the design stage and by genomic controlling in the data-analytic stage. The matching is based on a set of "stratum-delineating variables," such as, race, ethnicity, nationality, ancestry, and birthplace; and the genomic controlling is based on typing a number of null markers across the genome and applying the principle of multiplicative scaling of chi-square distribution. It pays to match carefully to have a higher proportion of correctly matched sets, as computer simulation showed that this would increase the power of the study. If matching is crude, one loses power but still has the correct type I error rate after genomic controlling. Power studies showed that the numbers of affected subjects required for the pair-matched study are comparable to those required by the case-parents design, if the study was conducted in a homogeneous population. As the (control-to-case) matching ratio increases, the number of affected subjects required decreases. With matching ratio tending toward infinity, the number required shrinks roughly by half. The case-control study with matching and genomic controlling frees us from family bondage, and the genetic problem as complicated as mapping genes can now be studied using simple epidemiologic methods.

Case-Control Studies↗
PubMed2002

A microsatellite-based multilocus screen for the identification of local selective sweeps.

With the availability of completely sequenced genomes, multilocus scans of natural variability have become a feasible approach for the identification of genomic regions subjected to natural and artificial selection. Here, I introduce a new multilocus test statistic, ln RV, which is based on the ratio of observed variances in repeat number at a set of microsatellite loci in two groups of populations. The distribution of ln RV values captures demographic history of the populations as well as variation in microsatellite mutation among loci. Given that microsatellite loci associated with a recent selective sweep differ from the remainder of the genome, they are expected to fall outside of the distribution of neutral ln RV values. The ln RV test statistic is applied to a data set of 94 loci typed in eight non-African and two African human populations.

Chromosome Mapping↗