SEARCH · PubMed Health

Results for “Models, Genetic”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed1987

Multivariate analysis of genetic and environmental influences for longitudinal height and weight data.

A multivariate analysis of genetic and environmental influences on longitudinal height and weight data from a Swedish twin sample is presented. For height in boys, genetic correlations of all ages with the first time point decrease during puberty and increase afterwards. A more linear pattern is evident for the girls. For weight in boys, genetic and environmental correlations are similar to the ones for height. Genetic correlations for girls are stable with age, while environmental correlations peak at 13.5 years and decrease drastically thereafter. The patterns for height and weight in boys suggest that a new set of genes may be turned on during puberty and turned off again afterwards. The pattern found for weight in girls indicates that a simple additive genetic model is not appropriate. It is necessary, however, to apply the model to actual data from several time points to recognize the inadequacy of the model.

Adolescent↗

PubMed2001

The 62E early-late puff of Drosophila contains D-spinophilin, an ecdysone-inducible PDZ-domain protein dynamically expressed during metamorphosis.

At the onset of metamorphosis in Drosophila melanogaster, the steroid hormone 20-OH ecdysone induces a small number of early and early-late puffs in the polytene chromosomes of the third-instar larval salivary gland whose activity is required for regulating the activity of a larger set of late puffs. Most of the corresponding early and early-late genes have been found to encode transcription factors that regulate a much larger set of late genes. In contrast, we describe here the identification of an ecdysone-regulated gene in the 62E early-late puff, denoted D-spinophilin, that encodes a protein similar to the mammalian protein spinophilin/neurabin II. The D-spinophilin protein is predicted to contain a highly conserved PP1-binding domain and adjacent PDZ domain, as well as a coiled-coil domain and SAM domain, and belongs to a family of related proteins from diverse organisms. Transcription of D-spinophilin is correlated with 62E puff activity during the early stages of metamorphosis and is ecdysone-dependent, making this the first member of this gene family shown to be regulated by a steroid hormone. Examination of the dynamic patterns of D-spinophilin expression during the early stages of metamorphosis are consistent with a role in central nervous system metamorphosis as well as a more general role in other tissues. As D-spinophilin appears to be the only member of this gene family in Drosophila, its study provides an excellent opportunity to elucidate the role of an important adaptor protein in a genetic model organism.

Amino Acid Sequence↗

PubMed1998

On the use of linear regression and maximum likelihood for QTL mapping in half-sib designs.

Methods of identification of quantitative trait loci (QTL) using a half-sib design are generally based on least-squares or maximum likelihood approaches. These methods differ in the genetical model considered and in the information used. Despite these differences, the power of the two methods in a daughter design in very similar. Using an analogy with a one-way analysis of variance, we propose an equation connecting the two test-statistics (F ratio for regression and likelihood ratio test in the case of the maximum likelihood). The robustness of this relationship is tested by simulation for different single QTL models. In general, the correspondence between the two statistics is good under both the null hypothesis and the alternative hypothesis of a single QTL segregating. Practical implications are discussed with particular emphasis on the theoretical distribution of the likelihood ratio test.

Chromosome Mapping↗

PubMed1998

Assortative mating for antisocial behavior: developmental and methodological implications.

Do people mate assortatively for antisocial behavior? If so, what are the implications for the development and persistence of antisocial behavior? We investigated assortative mating for antisocial behavior and its correlates in a sample of 360 couples from Dunedin, New Zealand. We found substantial assortative mating for self-reports of antisocial behavior per se and for self-reports of couple members' tendencies to associate with antisocial peers (0.54 on average). Perceptions about the likelihood of social sanctions for antisocial behavior (e.g., being caught by the authorities or losing the respect of one's family) showed moderate assortative mating (0.32 on average). However, assortative mating for personality traits related to antisocial behavior was low (0.15 on average). These findings suggest that, whereas assortative mating for many individual-difference variables (such as personality traits) is low, assortative mating for actual antisocial behaviors is substantial. We conclude that future family studies of antisocial behavior should endeavor to measure and understand the influence of assortative mating. In addition, we outline a testable behavior-genetic model for the development of antisocial behavior, in which genes and environments promoting or discouraging antisocial behavior become concentrated within families (due to assortative mating), giving rise to widely varying individual developmental trajectories that are, nevertheless, similar within families.

Adult↗

PubMed1999

Left-handedness as a function of sex, maternal versus paternal inheritance, and report bias.

The right-shift (RS) theory suggests that sex differences for handedness are due to the displacement of a chance distribution of asymmetry farther to the right in females than males by about 20%. An analysis of studies in the literature shows that when handedness is assessed by self-report, paired samples of males and females differ for incidence of left-handedness as predicted, but for parents assessed by indirect-report, there are fewer left-handed mothers than expected. When handedness is assessed by self-report in both generations, the RS genetic model successfully predicts the distribution in families. It is also successful at different levels of criterion from left-writing to non-right-handedness. The RS predictions are not always consistent with the findings of studies that depended on indirect report of parental handedness. When parental incidences are low the proportion of left-handed children in the families of left-handed mothers is higher than expected. When parental incidences are high, predictions for the families of left-handed mothers are excellent, but the percentage of left-handed children in the families of left-handed fathers is lower than expected. Data for all indirect-report studies are combined to test the idea that the chief cause of poor fit is underreporting of left-handed mothers by right-handed children. Transfer of right-handed children from R x R to R x L families, thereby raising the percentage of left-handed mothers by about 1%, is sufficient to give good fits to RS predictions for both sexes.

Adult↗

PubMed2002

Cdc25b phosphatase is required for resumption of meiosis during oocyte maturation.

In a wide variety of animal species, oocyte maturation is arrested temporarily at prophase of meiosis I (ref. 1). Resumption of meiosis requires activation of cyclin-dependent kinase-1 (CDK1, p34cdc2), one component of maturation-promoting factor (MPF). The dual specificity phosphatases Cdc25a, Cdc25b and Cdc25c are activators of cyclin-dependent kinases; consequently, they are postulated to regulate cell-cycle progression in meiosis and mitosis as well as the DNA-damage response. We generated Cdc25b-deficient (Cdc25b-/-) mice and found that they are viable. As compared with wildtype cells, fibroblasts from Cdc25b-/- mice grew vigorously in culture and arrested normally in response to DNA damage. Female Cdc25b-/- mice were sterile, and Cdc25b-/- oocytes remained arrested at prophase with low MPF activity. Microinjection of wildtype Cdc25b mRNA into Cdc25b-/- oocytes caused activation of MPF and resumption of meiosis. Thus, Cdc25b-/- female mice are sterile because of permanent meiotic arrest resulting from the inability to activate MPF. Cdc25b is therefore essential for meiotic resumption in female mice. Mice lacking Cdc25b provide the first genetic model for studying the mechanisms regulating prophase arrest in vertebrates.

Animals↗

PubMed2002

Optimal selection strategies for QTL mapping using pooled DNA samples.

The cost of large-scale association studies may be reduced substantially by analysis of pooled DNA from multiple individuals. Here we examine the optimal symmetric and asymmetric designs for pooling experiments for quantitative traits under a range of assumptions about the underlying genetic model and the sources of experimental errors in allele frequency estimation. The results indicate that, in the absence of experimental errors and for common alleles with additive effects, a symmetric pooling scheme comparing the top 27% with the bottom 27% of the trait distribution is optimal, extracting 80% the total information available. A symmetric design is not optimal for rare or recessive alleles, which require asymmetric (or other) pooling strategies. Allele frequency measurement errors reduce the optimal pooling fraction as well as the overall efficiency of the pooling design. In contrast, random variation in the amount of DNA contributed by individuals to a pool reduces only the overall efficiency of the pooling design. Our results emphasize the importance of minimising experimental errors and suggest a pooling fraction of around 20%.

Analysis of Variance↗

PubMed2003

PI3K/Akt and apoptosis: size matters.

Recent research has examined Akt and Akt-related serine-threonine kinases in signaling cascades that regulate cell survival and are important in the pathogenesis of degenerative diseases and in cancer. We seek to recapitulate the research that has helped to define the current understanding of the role of the Akt pathway under normal and pathologic conditions, also in view of genetic models of Akt function. In particular, we will evaluate the mechanisms of Akt regulation and the role of Akt substrates in Akt-dependent biologic responses in the decisions of cell death and cell survival. Here, we hope to establish the mechanisms of apoptosis suppression by Akt kinase as a framework for a more general understanding of growth factor-dependent regulation of cell survival.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed2002

Specific developmental gene silencing in the honey bee using a homeobox motif.

Manipulating the expression of genes in species that are not currently used as genetic models will provide comparative insights into the evolution of gene functions. However the experimental tools in doing so are limited in species that have not served as models for genetic studies. We have examined the effects of double stranded RNA (dsRNA) in the honey bee, an insect with considerably basic scientific interest. dsRNA derived from a 300 bp stretch of the E30 homeobox motif was injected into honey bee embryos at the anterior pole in the preblastoderm stage. We found that the dsRNA fragment successfully disrupted the protein expression of the target gene throughout the whole embryo. The disruption caused deficient phenotypes similar to known loss of function mutants of Drosophila engrailed, whereas embryos injected with nonsense dsRNA showed no abnormalities. We show that the large size of the honey bee egg (D: 0.3 mm, L: 1.6 mm) and the long preblastoderm stage (11-12 h) can be exploited to generate embryos with partial disruption of gene function, which may provide an elegant alternative to classical chimeric analyses. This is the first report of targeted disruption of gene function in the honey bee, and the results prove that the chosen target gene is a functional ortholog to engrailed in Drosophila.

Animals↗

PubMed2003

Phylogeography of lemmings (Lemmus): no evidence for postglacial colonization of Arctic from the Beringian refugium.

Beringia is considered as an important glacial refugium that served as the main source for colonization of formerly glaciated Arctic regions. To obtain high resolution views of Arctic refugial history, we examined mitochondrial cytochrome b phylogeography in the northern genus of rodents, Lemmus (true lemmings), sampled across its circumpolar distribution. Strong phylogeographical structure suggests vicariant separation over several glacial-interglacial periods and does not provide evidence supporting the importance of Beringia for extensive colonization of formerly glaciated regions. Rather than a source of postglacial colonization, Beringia represents an area of intraspecific endemism previously undetected by biogeographical analysis. Existing phylogeographical structure suggests that vicariant separation by glacial barriers was an important factor generating genetic divergence and, thus, increasing genetic diversity in lemmings on continental and circumpolar scales. However, there is little evidence for the direct effect of the last glaciation on the level of genetic variation and allele genealogy in lemmings on a regional geographical scale. This finding implies that the population genetic models of postglacial colonization suggested for temperate taxa might have limited applicability for Arctic species.

Animals↗

PubMed1997

Efficient gene targeting in the moss Physcomitrella patens.

The moss Physcomitrella patens is used as a genetic model system to study plant development, taking advantage of the fact that the haploid gametophyte dominates in its life cycle. Transformation experiments designed to target three single-copy genomic loci were performed to determine the efficiency of gene targeting in this plant. Mean transformation rates were 10-fold higher with the targeting vectors and molecular evidence for the integration of exogenous DNA into each targeted locus by homologous recombination is provided. The efficiency of gene targeting determined in these experiments is above 90%, which is in the range of that observed in yeast and several orders of magnitude higher than previous reports of gene targeting in plants. Thus, gene knock-out and allele replacement approaches are directly accessible to study plant development in the moss Physcomitrella patens. Moreover, efficient gene targeting has so far only been observed in lower eukaryotes such as protozoa, yeasts and filamentous fungi, and, as shown here the first example from the plant kingdom is a haplobiontic moss. This suggests a possible correlation between efficient gene targeting and haplophase in eukaryotes.

Bryopsida↗

PubMed1998

Evaluation of a restricted likelihood ratio test for mapping quantitative trait loci with extreme discordant sib pairs.

Risch and Zhang recently proposed to use extreme discordant sib pairs for mapping quantitative trait loci. Here, it is shown that the set of genetically possible distributions of the number of marker alleles in such sib-pairs is described by two inequalities. Thus, a likelihood ratio test analogous to Holmans's possible triangle test for affected sib pairs can be defined. The performance of this test is compared to the mean test considered by Risch and Zhang. For most of the genetic models considered, the mean test is slightly more powerful than the restricted likelihood ratio test. However, for models with a rare recessive gene (or equivalently a common dominant gene), the restricted likelihood ratio test is much more powerful.

Alleles↗

PubMed2005

Loss of the limbic mineralocorticoid receptor impairs behavioral plasticity.

Corticosteroid action in the brain is mediated by the mineralocorticoid (MR) and the glucocorticoid (GR) receptor. Disturbances in MR- and GR-mediated effects are thought to impair cognition, behavior, and endocrine control. To assess the function of the limbic MR in these processes, we inactivated the MR gene in the forebrain of the mouse using the Cre/loxP-recombination system. We screened the mice with a limbic MR deficiency in various learning and exploration tests. The mutant mice show impaired learning of the water-maze task and deficits in measures of working memory on the radial maze due to behavioral perseverance and stereotypy. They exhibit a hyperreactivity toward a novel object but normal anxiety-like behavior. The behavioral changes are associated with abnormalities of the mossy fiber projection and an up-regulation of GR expression in the hippocampus. Adult mutant mice show normal corticosterone levels at circadian trough and peak. This genetic model provides important information about the consequences of a permanently altered balance between limbic MR and GR, with implications for stress-related neuroendocrine and neuropsychiatric diseases.

Animals↗

PubMed1983

On the optimal sex ratio.

The equilibrium structures for various multiallele sex-determining genetic models of panmictic populations with sex expression depending on the genotypes of either the zygote or a parent are described. Even-sex-ratio equilibrium surfaces can exist apart from equilibrium points having coincident male and female allelic frequency sets. The latter (symmetric) equilibrium states entail biased sex ratios. A stable symmetric equilibrium and an even-sex-ratio equilibrium segregating the same alleles cannot coexist. The tendency to evolve toward an even-sex ratio is embodied by the following optimality property: starting from an equilibrium having a biased sex ratio, mutant sex-determining alleles can accumulate only in the case in which in the augmented system all attainable equilibrium states have a sex ratio closer to one to one.

Alleles↗

PubMed2003

Adipocyte-selective reduction of the leptin receptors induced by antisense RNA leads to increased adiposity, dyslipidemia, and insulin resistance.

Although recent evidence suggests that leptin can directly regulate a wide spectrum of peripheral functions, including fat metabolism, genetic examples are still needed to illustrate the physiological significance of direct actions of leptin in a given peripheral tissue. To this end, we used a technical knock-out approach to reduce the expression of leptin receptors specifically in white adipose tissue. The evaluation of leptin receptor reduction in adipocytes was based on real time PCR analysis of the mRNA levels, Western blot analysis of the proteins, and biochemical analysis of leptin signaling capability. Despite a normal level of leptin receptors in the hypothalamus and normal food intake, mutant mice developed increased adiposity, decreased body temperature, hyperinsulinemia, hypertriglyceridemia, impaired glucose tolerance and insulin sensitivity, as well as elevated hepatic and skeletal muscle triglyceride levels. In addition, a variety of genes involved in regulating fat and glucose metabolism were dysregulated in white adipose tissue. These include tumor necrosis factor-alpha, adiponectin, leptin, fatty acid synthase, sterol regulatory element-binding protein 1, glycerol kinase, and beta3-adrenergic receptor. Furthermore, the mutant mice are significantly more sensitive to high fat feeding with regard to developing obesity and severe insulin resistance. Thus, we provide a genetic model demonstrating the physiological importance of a peripheral effect of leptin in vivo. Importantly, this suggests the possibility that leptin resistance at the adipocyte level might be a molecular link between obesity and type 2 diabetes.

Adipocytes↗

PubMedDate not supplied

Genetic analyses of aging processes in Drosophila.

Genetic investigations into the aging processes of Drosophila have a long history. Much of the earlier work attempted the analysis of longevity in already existing and (usually) short-lived strains and mutants, but was unsuccessful because there was no way of assuring that the genes involved actually affected the normal aging processes. Success was achieved only when procedures were devised to specifically select for mutants and/or strains affecting the normal aging processes. Recent work has shown that the life span may be genetically altered either via an acceleration of the normal aging rate or via the stage-specific lengthening of certain portions of the adult life span. A variety of evidence suggests that aging is best viewed as a genetically determined, environmentally modulated, event dependent process. The evidence underlying these observations is discussed, a possible genetic model is presented and future directions are suggested.

Aging↗

PubMed2001

A survey of affected-sibship statistics for nonparametric linkage analysis.

We have compared the power of a large number of allele-sharing statistics for "nonparametric" linkage analysis with affected sibships. Our rationale was that there is an extensive literature comparing statistics for sibling pairs but that there has not been much guidance on how to choose statistics for studies that include sibships of various sizes. We concentrated on statistics that can be described as assigning scores to each identity-by-descent-sharing configuration that a pedigree might take on (Whittemore and Halpern 1994). We considered sibships of sizes two through five, 27 different genetic models, and varying recombination fractions between the marker and the trait locus. We tried to identify statistics whose power was robust over a wide variety of models. We found that the statistic that is probably used most often in such studies-S(all)-performs quite well, although it is not necessarily the best. We also found several other statistics (such as the R criterion, S(robdom), and the Sobel-and-Lange statistic C) that perform well in most situations, a few (such as S(-#geno) and the Feingold-and-Siegmund version of S(pairs)) that have high power only in very special situations, and a few (such as S(-#geno), the N criterion, and the Sobel-and-Lange statistic B) that seem to have low power for the majority of the trait models. For the most part, the same statistics performed well for all sibship sizes. We also used our results to give some suggestions regarding how to weight sibships of different sizes, in forming an overall statistic.

Alleles↗

PubMed2003

Coevolution in variable mutualisms.

Many mutualistic interactions are probably not mutualistic across all populations and years. This article explores consequences of this observation with a series of genetic models that consider how variable mutualisms coevolve. The first models, previously introduced in a general coevolutionary context, consider two coevolving species whose fitness interactions change between beneficial and antagonistic in response to independent spatial or temporal variation in the abiotic or biotic environment. The results demonstrate that both temporal and spatial variability in fitness interactions can cause partner species with tightly matched traits favored by unconditional mutualisms to be vulnerable to evolutionary invasion by alternative types. A new model presented here shows that an additional mutualistic species can have a similar effect and can even cause fitness interactions between the other two species to evolve. Under some conditions, the pairwise interactions can change unidirectionally from mutualistic to antagonistic, with virtually no evolutionary change in either partner species. In other cases, fitness interactions between the species pair can oscillate between mutualism and antagonism as a result of coevolution in the third species. Taken as a whole, these theoretical results suggest that many features of mutualistic coevolution can best be understood by considering spatial, temporal, and community-dependent patterns of fitness interactions.

Biological Evolution↗