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PubMed1991

Strain differences in the pattern and intensity of wheel running activity in laboratory rats.

Wheel running activity rhythms of three inbred rat strains, ACI/Ztm, BH/Ztm, and LEW/Ztm, were compared in order to evaluate the effect of genetic differences on circadian rhythm parameters. Significant strain differences were found in the general pattern of the activity rhythms and their characteristic periodicities as well as in the amount and duration of wheel running activity and the timing of activity onsets and offsets. The results suggest that genetic differences exist in the coupling of the multiple circadian oscillators that generate the overall pattern of wheel running activity.

Activity Cycles↗
PubMed2000

Evaluation of Egyptian sheep production systems: I. Breed crosses and management systems.

Our objective was to evaluate life-cycle performance of flocks of two Egyptian breeds, Rahmani (R) and Ossimi (O), and their crosses with Finnish Landrace (F) in two management systems. Management systems were one mating season per year (1M) and three mating seasons per 2 yr (3M). Breeds and crosses studied included purebred R and O, F1 crosses 1/2F-1/2R (FR) and 1/2F-1/2O (FO), and inter se matings of 1/4 F-3/4 R (RFR) and 1/4 F-3/4 O (OFO). A dynamic computer model was used to simulate animal performance and enterprise efficiency and profit. Two measures of lifecycle feed conversion (biological efficiency) were computed: kilograms of TDN input per kilograms of empty body weight output (TDN/EBW) and kilograms of TDN input per kilogram of carcass lean output (TDN/CLN). Profit was measured as gross margin (income minus variable costs per ewe per year, GM/EWE). Input parameters for the model were obtained from published results and analyses of data collected from experimental flocks of the same genetic stocks in Egypt. Profit for FR and RFR was 42 and 6% higher in 1M than in 3M. However, profit for all other genetic types was 4 to 8% greater in 3M than in 1M. Breed rankings changed depending on the measure of evaluation (i.e., biological efficiency or profit). Maximization of system output did not necessarily improve efficiency. Under accelerated lambing systems, greater overhead costs associated with labor and feed offset gains in ewe productivity. Genetic stocks should be matched to resources and management systems.

Animal Husbandry↗
PubMed1985

Neural plasticity in schizophrenia.

No current biological hypothesis can assimilate the genetic, environmental, and clinical features of schizophrenia. If, as some authors contend, environmental factors have important effects on the course of schizophrenia, then a fruitful research concern may be the adaptation of neuronal circuitry to environmental changes. The plasticity of neuronal connections has been studied by subjecting animals to neurosurgical lesions, brain electro-stimulation, and a variety of rearing environments. The present article approaches the schizophrenia research literature from a theoretical perspective which takes into account the plasticity of neuronal connections. In a speculative manner, it demonstrates how neural plasticity concepts can be invoked to explain the following seemingly disparate features of schizophrenia: the pharmacological support for the dopamine hypothesis, the delayed onset and offset of neuroleptic antipsychotic action, genetic and environmental influences in schizophrenia, the regional alterations in brain structure and function seen in chronic schizophrenic patients, and the various types of behavioral symptoms exhibited by schizophrenic patients. In view of the explanatory potential of neural plasticity concepts, a research program that focuses on these concepts seems warranted.

Animals↗
PubMed1994

International Commission for Protection Against Environmental Mutagens and Carcinogens. Deoxyribonucleoside triphosphate levels: a critical factor in the maintenance of genetic stability.

DNA precursor pool imbalances can elicit a variety of genetic effects and modulate the genotoxicity of certain DNA-damaging agents. These and other observations indicate that the control of DNA precursor concentrations is essential for the maintenance of genetic stability, and suggest that factors which offset this control may contribute to environmental mutagenesis and carcinogenesis. In this article, we review the biochemical and genetic mechanisms responsible for regulating the production and relative amounts of intracellular DNA precursors, describe the many outcomes of perturbations in DNA precursor levels, and discuss implications of such imbalances for sensitivity to DNA-damaging agents, population monitoring, and human diseases.

Animals↗
PubMed2025

Conservation genomics of a threatened subtropical Rhododendron species highlights the distinct conservation actions required in marginal and admixed populations.

With the impact of climate change and anthropogenic activities, the underlying threats facing populations with different evolutionary histories and distributions, and the associated conservation strategies necessary to ensure their survival, may vary within a species. This is particularly true for marginal populations and/or those showing admixture. Here, we re-sequence genomes of 102 individuals from 21 locations for Rhododendron vialii, a threatened species distributed in the subtropical forests of southwestern China that has suffered from habitat fragmentation due to deforestation. Population structure results revealed that R. vialii can be divided into five genetic lineages using neutral single-nucleotide polymorphisms (SNPs), whereas selected SNPs divide the species into six lineages. This is due to the Guigu (GG) population, which is identified as admixed using neutral SNPs, but is assigned to a distinct genetic cluster using non-neutral loci. R. vialii has experienced multiple genetic bottlenecks, and different demographic histories have been suggested among populations. Ecological niche modeling combined with genomic offset analysis suggests that the marginal population (Northeast, NE) harboring the highest genetic diversity is likely to have the highest risk of maladaptation in the future. The marginal population therefore needs urgent ex situ conservation in areas where the influence of future climate change is predicted to be well buffered. Alternatively, the GG population may have the potential for local adaptation, and will need in situ conservation. The Puer population, which carries the heaviest genetic load, needs genetic rescue. Our findings highlight how population genomics, genomic offset analysis, and ecological niche modeling can be integrated to inform targeted conservation.

Rhododendron↗
PubMed1991

Use of an animal model in situations of limited subclass numbers and high degrees of relationships.

Breeding value estimation procedures for two traits with moderate and high heritability were evaluated by using a single-trait animal model and computer-simulated data designs. Of interest were the effects of differing numbers of animals and degrees of relationships among animals within and across contemporary groups (tests). Test effects were assumed fixed and animal effects were assumed random. Family size, number of families per contemporary group, and degree of genetic relationships within and across contemporary groups were varied to determine interrelationships among the factors. Results were compared on the basis of accuracy by using both the correlation of true and estimated breeding values and the prediction error variance obtained from the inverse of the coefficient matrix of the mixed-model equations. Small contemporary groups in conjunction with evaluation of closely related families caused average accuracy to decrease relative to that obtained with the same number of unrelated animals because genetically related animals were less accurately evaluated relative to one another. Connecting contemporary groups with a genetic relationship matrix formed a large set of interdependent equations and improved the average accuracy of predicted breeding values. The slight decrease in accuracy for genetically related animals was more than offset by the increase in accuracy of evaluation for their unrelated test mates because the proportion of fixed effects to random effects was smaller. Care must be exercised in designing evaluation schemes involving small populations, and the decision of which fixed effects to include in the model is critical.

Animals↗
PubMed2000

A high-resolution radiation hybrid map of the proximal portion of mouse chromosome 5.

Radiation hybrid (RH) mapping of the mouse genome provides a useful tool in the integration of existing genetic and physical maps, as well as in the ongoing effort to generate a dense map of expressed sequence tags. To facilitate functional analysis of mouse Chromosome 5, we have constructed a high-resolution RH map spanning 75 cM of the chromosome. During the course of these studies, we have developed RHBase, an RH data management program that provides data storage and an interface to several RH mapping programs and databases. We have typed 95 markers on the T31 RH panel and generated an integrated map, pooling data from several sources. The integrated RH map ranges from the most proximal marker, D5Mit331 (Chromosome Committee offset, 3 cM), to D5Mit326, 74.5 cM distal on our genetic map (Chromosome Committee offset, 80 cM), and consists of 138 markers, including 89 simple sequence length polymorphic markers, 11 sequence-tagged sites generated from BAC end sequence, and 38 gene loci, and represents average coverage of approximately one locus per 0.5 cM with some regions more densely mapped. In addition to the RH mapping of markers and genes previously localized on mouse Chromosome 5, this RH map places the alpha-4 GABA(A) receptor subunit gene (Gabra4) in the central portion of the chromosome, in the vicinity of the cluster of three other GABA(A) receptor subunit genes (Gabrg1-Gabra2-Gabrb1). Our mapping effort has also defined a new cluster of four genes in the semaphorin gene family (Sema3a, Sema3c, Sema3d, and Sema3e) and the Wolfram syndrome gene (Wfs1) in this region of the chromosome.

Animals↗
PubMed2004

Genetic mapping of activity determinants within cellular prion proteins: N-terminal modules in PrPC offset pro-apoptotic activity of the Doppel helix B/B' region.

The PrP-like Doppel (Dpl) protein causes apoptotic death of cerebellar neurons in transgenic mice, a process prevented by expression of the wild type (wt) cellular prion protein, PrP(C). Internally deleted forms of PrP(C) resembling Dpl such as PrPDelta32-121 produce a similar PrP(C)-sensitive pro-apoptotic phenotype in transgenic mice. Here we demonstrate that these phenotypic attributes of wt Dpl, wt PrP(C), and PrPDelta132-121 can be accurately recapitulated by transfected mouse cerebellar granule cell cultures. This system was then explored by mutagenesis of the co-expressed prion proteins to reveal functional determinants. By this means, neuroprotective activity of wt PrP(C) was shown to be nullified by a deletion of the N-terminal charged region implicated in endocytosis and retrograde axonal transport (PrPDelta23-28), by deletion of all five octarepeats (PrPDelta51-90), or by glycine replacement of four octarepeat histidine residues required for selective binding of copper ions (Prnp"H/G"). In the case of Dpl, overlapping deletions defined a requirement for the gene interval encoding helices B and B' (DplDelta101-125). These data suggest contributions of copper binding and neuronal trafficking to wt PrP(C) function in vivo and place constraints upon current hypotheses to explain Dpl/PrP(C) antagonism by competitive ligand binding. Further implementation of this assay should provide a fuller understanding of the attributes and subcellular localizations required for activity of these enigmatic proteins.

Alleles↗
PubMed2026

Genomic-Environmental Integration Predicts Climate Vulnerability and Adaptive Potential of Tibetan Plateau Herpetofauna.

The herpetofauna of the Tibetan Plateau, home to Earth's highest-elevation ectothermic vertebrates, face escalating threats from rapid climate change. However, conventional conservation strategies often overlook intraspecific genetic variation and adaptive potential, limiting their predictive accuracy and effectiveness. Here, we integrate whole-genome resequencing data with environmental modeling to assess climate vulnerability in two endemic species: Nanorana parkeri (Tibetan frog) and Thermophis baileyi (hot-spring snake). Results suggest that the western populations of the two species exhibit higher genomic offsets under future climate, while some eastern populations of the Tibetan frog face a decrease in niche suitability, and the hot-spring snake will experience varying degrees of loss of suitable habitats. Furthermore, heterozygosity, genetic diversity, and genetic load demonstrate significant correlations with genomic offsets, suggesting that low genetic diversity and high genetic load may weaken the potential to adapt to environmental changes. Based on a genome-niche index that combines genomic offsets with niche suitability change, we identified evolutionary rescue populations that are potentially tolerant to climate change. Our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive potential and enable effective conservation management of high-altitude herpetofauna under rapid climate change.

Animals↗
PubMed2004

Impact of nonrandom mating on genetic variance and gene flow in populations with mass selection.

The mechanisms by which nonrandom mating affects selected populations are not completely understood and remain a subject of scientific debate in the development of tractable predictors of population characteristics. The main objective of this study was to provide a predictive model for the genetic variance and covariance among mates for traits subjected to directional selection in populations with nonrandom mating based on the pedigree. Stochastic simulations were used to check the validity of this model. Our predictions indicate that the positive covariance among mates that is expected to result with preferential mating of relatives can be severely overpredicted from neutral expectations. The covariance expected from neutral theory is offset by an opposing covariance between the genetic mean of an individual's family and the Mendelian sampling term of its mate. This mechanism was able to predict the reduction in covariance among mates that we observed in the simulated populations and, in consequence, the equilibrium genetic variance and expected long-term genetic contributions. Additionally, this study provided confirmatory evidence on the postulated relationships of long-term genetic contributions with both the rate of genetic gain and the rate of inbreeding (deltaF) with nonrandom mating. The coefficient of variation of the expected gene flow among individuals and deltaF was sensitive to nonrandom mating when heritability was low, but less so as heritability increased, and the theory developed in the study was sufficient to explain this phenomenon.

Genetic Variation↗
PubMed1996

The causes of essential hypertension.

1. Confusion between the criteria for defining and diagnosing hypertension may have misled the search for the causes of hypertension. 2. The systematic approach of molecular genetics appears to offer the best chance of explaining hypertension, but the attractions are partly offset by the large numbers required, and unproven record of the genetic techniques in finding functional mutations in complex human disorders. 3. Part of the evidence for the polygenic nature of essential hypertension derives from the variable response to a large number of different anti-hypertensive agents. Systematic investigation of this variability may provide a basis for dividing patients into genetically more homogeneous sub-groups, within which smaller numbers will be required to detect the genes responsible for the susceptibility to hypertension. 4. The proportion of hypertensive patients with affected siblings has been studied in 6000 patients from Addenbrookes Hospital and local general practices. A recurrence risk for hypertension of approximately 3.5 was found. 5. Approximately two-thirds of patients have no known affected siblings. The next largest group, about one third, is patients whose siblings are all hypertensive. In a small group, < 10% of all patients, half the siblings are hypertensive. 6. We conclude from these surprising findings that hypertension is not a continuous, multifactorial part of the normal blood pressure distribution. They suggest that several more single-gene disorders causing hypertension will be found. The sibships where all members are hypertensive are inconsistent with the segregation of Mendelian genetics and suggest the selection of some genes linked to hypertension at the time of gamete maturation.

Genetic Predisposition to Disease↗
PubMed2002

Identification of multicopy suppressors of the pcnB plasmid copy number defect in Escherichia coli.

Plasmids containing a ColE1 origin of replication are widely used for cloning purposes in Escherichia coli. Among the host factors that affect the copy number of ColE1 plasmids is the E. coli protein poly(A) polymerase I (PAP I), which regulates the intracellular level of RNA I, a ColE1-encoded negative regulator of plasmid replication. In strains that lack PAP I, RNA I levels are elevated, resulting in reduced levels of ColE1 plasmids in the cell. PAP I is encoded by the gene pcnB. We devised a genetic approach, based on the identification of multicopy suppressor clones, to identify trans-acting factors that can help offset the ColE1 plasmid copy number defect in a pcnB (-) genetic background. Using this strategy, we identified suppressors that mapped to two regions of the E. coli chromosome. The suppressor activity of one of the chromosomal regions was localized to the rssB gene, a response regulator gene known to be involved in the turnover of the stationary-phase sigma factor, RpoS. The second suppressor maps to min 55.4 of the E. coli chromosome, and the factor responsible for the suppressor activity appears to be a novel RNA or protein.

Bacterial Proteins↗
PubMed1996

The consequences of phenotypic plasticity in cyclically varying environments: a genetic algorithm study.

By "phenotypic plasticity" we refer to the capacity of a genotype to exhibit different phenotypes, whether in the same or in different environments. We have previously demonstrated that phenotypic plasticity can improve the degree of adaptation achieved via natural selection (Behera & Nanjundiah, 1995). That result was obtained from a genetic algorithm model of haploid genotypes (idealized as one-dimensional strings of genes) evolving in a fixed environment. Here, the dynamics of evolution is examined under conditions of a cyclically varying environment. We find that the rate of evolution, as well as the extent of adaptation (as measured by mean population fitness) is lowered because of environmental cycling. The decrease in adaptation caused by a varying environment can, however, be partly or wholly compensated by an increase in the degree of plasticity that a genotype is capable of. Also, the reduction of population fitness caused by a variable environment can be partially offset by decreasing the total number of genetic loci. We conjecture that an increase in genome size may have been among the factors responsible for the evolution of phenotypic plasticity.

Adaptation, Physiological↗
PubMed2004

Metabolic profiling of leaves and fruit of wild species tomato: a survey of the Solanum lycopersicum complex.

The domestication of the tomato Solanum lycopersicum and associated selective pressures eventually led to the large-fruited varieties cultivated today. S. lycopersicum varieties are generally red-fruited, but display considerable variance in fruit colour intensity, shape, and quality. The increase in productivity on cultivation is, however, somewhat offset by the narrowing of the crops genetic base which leads to increased susceptibility to biotic and abiotic stresses. Since S. lycopersicum can easily be crossed with its wild species relatives, this exotic germplasm can provide a valuable source for the improvement of agriculturally important traits. A GC-MS based survey is presented here of the relative metabolic levels of leaves and fruit of S. lycopersicum and five wild species of tomato that can be crossed with it (S. pimpinellifolium, S. neorickii, S. chmielewskii, S. habrochaites, and S. pennellii). Changes in metabolite contents were identified in the wild species that are potentially important with respect to stress responses, as well as in metabolites of nutritional importance. The significance of these changes is discussed with respect to the use of the various wild species for metabolic engineering within wide breeding strategies.

Fruit↗
PubMed2003

Interactions of genes and environment in myopia.

Myopia is a condition in which the eye is too long for the focal length of cornea and lens, and the plane of sharp focus ends up in front of the retina. Given that the growth of the length of the eye is normally controlled with extreme precision by an image-processing feedback mechanism in the retina, myopia can either be the result of inappropriate visual stimulation, genetically determined changes in the gain or offset of the feedback loops or of inappropriate responses of the target tissues. There is no doubt that an environmental component is involved and extended near work appears to be the major risk factor. However, there is also no doubt that myopia is inherited since myopic parents are much more likely to have myopic children, and myopia is far more frequent in Asian populations than in the USA or Europe, even if groups are compared that have performed similar amounts of near work. A number of systemic or ophthalmic diseases are associated with myopia, indicating that metabolic conditions may interfere either with the gains of the feedback loops or the responses of the target tissue, the sclera. Since there is still no therapy against myopia development, research is directed toward the identification of genes that control the axial elongation of the eye.

Animals↗
PubMed1992

Selection for postweaning growth in inbred Hereford cattle: the Fort Keogh, Montana line 1 example.

Demographic characteristics and genetic trends in birth weight and pre- and postweaning ADG were examined in a population of Hereford cattle (Line 1). Line 1 was founded largely from two paternal half-sib sires and has been selected for postweaning growth. There were pedigree records on 951 members of the base population that predated 1935, when data collection began. Numbers of records analyzed using mixed-model methodology were 4,716 birth weight, 4,427 preweaning ADG, and 3,579 postweaning ADG. Birth weight and preweaning ADG were considered to have direct and maternal genetic components. Inbreeding accumulated rapidly from 1935 to 1960 and more slowly (.22%/yr) thereafter. Any reduction in additive genetic variance due to inbreeding and selection may have been offset by a concurrent reduction in generation interval that was observed as time progressed. Expected selection differential for 365-d weight, averaged over sexes, was 31.2 kg per generation. For birth weight, annual genetic trends in direct and maternal effects were 42 +/- 3 g and 15 +/- 3 g, respectively. Annual direct and maternal genetic trends for preweaning ADG were .70 +/- .06 g/d and .63 +/- .06 g/d, respectively. Direct response in postweaning ADG was linear and equal to 5.3 +/- .6 g.d-1.yr-1. As a result, estimated breeding values of birth weight, 200-d weight, and 365-d weight increased by 3.2 kg, 14.5 kg, and 62.4 kg, respectively, from 1935 to 1989. Selection within Line 1 was effective in increasing genetic potential for growth over 13 generations. No selection plateau was observed in any of the traits examined.

Age Factors↗
PubMed1996

Total hip replacement: a study of customized prostheses.

The majority of widely used hip prostheses offer a limited range of offset sizes, including 35, 37, 40, 44 and 45mm. These sizes are provided to match the mean population offset which has been reported as 43.0mm (Noble et al 1988). The variability of proximal femoral geometry in terms of offset is consistent with the theory that the geometry of the femur is determined by a large number of genetic and environmental factors (Ericksen 1979). This paper suggests that the range in offset sizes offered by off-the-shelf hip protheses is not sufficient to match the extremes of anatomical offset variability of the Northern Ireland sample studied and that a custom stem that matches more accurately key femoral dimensions such as offset, may be more desirable.

Clinical Nursing Research↗
PubMed2006

The costs and benefits of genetic heterogeneity in resistance against parasites in social insects.

The occurrence of polygyny and polyandry in social insects has long puzzled evolutionary biologists. If cooperation requires genetic relatedness, how do we explain the occurrence and maintenance of mechanisms that reduce the degree of relatedness among colony members? A much-discussed hypothesis states that genetically diverse colonies are more resistant to parasitism than homogenous colonies because genetic diversity reduces the spread of a disease within a colony. However, as we will argue in this note, a necessary condition for the parasite hypothesis is that genetically heterogeneous colonies have a larger suite of parasites that are capable of infecting them. This implicit relationship is important because it implies that even if the cost per infection is reduced, this may not be sufficient to offset the increased rate of acquiring infections. The advantages of genetic heterogeneity as a defense against parasites thus may not be as big as commonly thought.

Animals↗