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At least 919 records · Page 51Linked to original sources

PubMed2000

Adaptation to marginal habitats: contrasting influence of the dispersal rate on the fate of alleles with small and large effects.

The focus of this paper is the relationship between the dispersal rate and the conditions for invasion of a rare allele that improves performance in a marginal sink habitat at the expense of reducing fitness in the main source habitat. Classic multiple-niche population-genetic models predict that the conditions for the invasion of such an allele always become more favourable as the dispersal rate decreases. Precisely the opposite prediction was reached in demographic fitness-sensitivity studies. This study reconciles those contradictory predictions and identifies the assumptions responsible for the discrepancy. I show that whether a lower dispersal rate makes the conditions for the invasion of the allele more or less stringent depends on the magnitude of the effects of the allele. If the effect is large relative to the degree of maladaptedness of the original genotype to the marginal habitat, the conditions become less stringent with decreasing dispersal rate. The opposite is the case for mutations with very small effects. For a broad range of mutations with intermediate effects the conditions are most stringent under an intermediate dispersal rate.

Alleles↗

PubMed1984

Evidence for two control genes regulating expression of the quinic acid utilization (qut) gene cluster in Aspergillus nidulans.

The first three steps in quinic acid degradation in Aspergillus nidulans are catalysed by highly inducible enzymes encoded by a gene cluster regulated by an adjacent control region. Analysis of two non-inducible mutants has been done in diploid strains, where qutA8 is recessive and all three enzyme activities are fully induced in heterozygous qutA8/qutA+ diploids. In contrast, qutA4/qutA+ heterozygous diploids show semi-dominance of the mutant allele, giving markedly diminished growth on quinic acid and 30-40% decrease of enzyme induction. Strikingly, the qutA4/qutA8 heterozygous diploid grows to the same degree on quinic acid as the qutA4/qutA+ heterozygote and shows the same level of enzyme induction, whereas both the homozygous mutant diploids do not grow on quinic acid and show no enzyme induction. Therefore the two mutant genomes complement, identifying two distinct regulatory gene functions. A genetic model is proposed of a negatively acting gene (qutA) repressing expression of a positively acting gene (qutD, previously designated qutA8+) whose product is in turn required for expression of the three structural genes. The qutA4 mutation is interpreted to produce an altered repressor insensitive to quinic acid, and the qutD8 mutation the loss of activator protein. Close similarity in the regulation of the quinic acid gene cluster in Neurospora crassa suggests that the two types of control mutation, qalS and qalF, described for N. crassa may also reflect two regulatory genes.

Alcohol Oxidoreductases↗

PubMed2003

Coevolution of an avian host and its parasitic cuckoo.

We use a quantitative genetic model to examine the coevolution of host and cuckoo egg characters (termed "size" as a proxy for general appearance), host discrimination, and host and cuckoo population dynamics. A host decides whether to discard an egg using a comparison of the sizes of the eggs in her nest, which changes as host and cuckoo eggs evolve. Specifically, we assume that the probability that she discards the largest egg in her nest depends on how much larger it is than the second largest egg. This decision rule (i.e., the acceptable difference in egg sizes) also evolves, changing both the chance of successful rejection of a cuckoo egg in parasitized nests and the chance of mistaken rejection of a host egg in both parasitized and unparasitized nests. We find a stable equilibrium for coexistence of the host and cuckoo where there is cuckoo egg mimicry, evolutionary displacement of the host egg away from the cuckoo egg phenotype, and host discrimination against unusual eggs. Both host discrimination and host egg displacement are fairly weak at the equilibrium. Cuckoo egg mimicry, although imperfect, usually evolves more extensively and quickly than the responses of the host. Our model provides evidence for both the evolutionary equilibrium and evolutionary lag hypotheses of host acceptance of parasitic eggs.

Animals↗

PubMed1993

Heredity, molecular genetics and colorectal cancer: a review.

It is estimated that the hereditary polyposis and non-polyposis colorectal cancer (CRC) syndromes, which have an autosomal dominant pattern of inheritance, represent less than 10% of the total CRC burden. Thus, more than 90% of all cases of CRC have previously been considered to arise 'sporadically', with no identifiable genetic link. However, recent clinical evidence now suggests that a significant proportion of CRC seen in the general population may involve an inherited genetic susceptibility. Therefore, constructing an accurate family tree on all patients with a family history of CRC is an essential part of identifying families with an increased risk for CRC who could then be offered screening. Also, molecular genetic study of colorectal adenomas and carcinomas has led to a proposed genetic model of colorectal tumorigenesis which involves interactions between oncogenes and tumour suppressor genes. This information has important potential implications for screening, determining prognosis and for providing multiple targets for altering the sequence of malignant transformation.

Colorectal Neoplasms↗

PubMed1995

Are anxiety symptoms in childhood heritable?

Although childhood anxiety appears to aggregate in families, transmission could be explained by both genetic and shared environmental factors. Twin studies can be used to disentangle genetic and environmental effects. In this study, a systematically ascertained sample of twins was used to investigate whether anxiety symptoms are heritable. Parent-rated anxiety symptoms could best be explained by an additive genetic model with heritability estimated at 59%. However, when self ratings were analysed (in the adolescent subsample), familial transmission could be accounted for by shared environmental factors only.

Adolescent↗

PubMed2004

Familial influences on sustained attention and inhibition in preschoolers.

BACKGROUND: In this study several aspects of attention were studied in 237 nearly 6-year-old twin pairs. Specifically, the ability to sustain attention and inhibition were investigated using a computerized test battery (Amsterdam Neuropsychological Tasks). Furthermore, the Teacher's Report Form (TRF) was filled out by the teacher of the child and the attention subscale of this questionnaire was analyzed. METHODS: The variance in performance on the different tasks of the test battery and the score on the attention scale of the TRF were decomposed into a contribution of the additive effects of many genes (A), environmental effects that are shared by twins (C) and unique environmental influences not shared by twins (E) by using data from MZ and DZ twins. RESULTS: The genetic model fitting results showed an effect of A and E for the attention scale of the TRF, and for some of the inhibition and sustained attention measures. For most of the attention variables, however, it was not possible to decide between a model with A and E or a model with C and E. Time-on-task effects on reaction time or number of errors and the delay after making an error did not show familial resemblances. A remarkable finding was that the heritability of the attention scale of the TRF was found to be higher than the heritability of indices that can be considered to be more direct measures of attention, such as mean tempo in the sustained attention task and response speed in the Go-NoGo task. CONCLUSION: In preschoolers, familial resemblances on sustained attention and inhibition were observed.

Attention↗

PubMed1998

Intracellular recordings in thalamic neurones during spontaneous spike and wave discharges in rats with absence epilepsy.

1. In vivo extracellular and intracellular recordings were performed from thalamocortical (TC) neurones in a genetic model of absence epilepsy (genetic absence epilepsy rats from Strasbourg) during spontaneous spike and wave discharges (SWDs). 2. Extracellularly recorded single units (n = 14) fired either a single action potential or a high frequency burst of up to three action potentials, concomitantly with the spike component of the spike-wave complex. 3. Three main events characterized the intracellular activity of twenty-six out of twenty-eight TC neurones during SWDs: a small amplitude tonic hyperpolarization that was present throughout the SWD, rhythmic sequences of EPSP/IPSPs occurring concomitantly with the spike-wave complexes, and a small tonic depolarization at the end of the SWD. The rhythmic IPSPs, but not the tonic hyperpolarization, were mediated by activation of GABAA receptors since they reversed in polarity at -68 mV and appeared as depolarizing events when recording with KCl-filled electrodes. 4. The intracellular activity of the remaining two TC neurones consisted of rhythmic low threshold Ca2+ potentials, with a few EPSP/IPSP sequences present at the start of the SWD. 5. These results obtained in a well-established genetic model of absence epilepsy do not support the hypothesis that the intracellular activity of TC neurones during SWDs involves rhythmic sequences of GABAB IPSPs and low threshold Ca2+ potentials.

Action Potentials↗

PubMed1999

Epilepsy and EEG findings in males with fragile X syndrome.

PURPOSE AND METHODS: One hundred and ninety-two fragile X male patients were investigated for seizures and EEG findings, 168 in a retrospective and 24 in another prospective study, to characterize the natural history of seizures, epilepsy, and EEG abnormalities in males with this syndrome. RESULTS: Seizures were documented in 35 (18.2%) of 192 patients; they never started before the age of 2 years or after the age of 9 years. Seizures were frequently of the complex partial type and less frequently of the partial motor and generalized type. Seizures involving frontal and temporal lobes were commonly seen and were usually well controlled by anticonvulsants. In the majority of young fragile X patients studied, an age-related paroxysmal EEG pattern was found, which showed neurophysiologic characteristics very similar to those of the centrotemporal spikes. CONCLUSIONS: These findings confirm that fragile X syndrome can be considered a genetic model of epilepsy.

Adolescent↗

PubMed1996

Voluntary alcohol consumption in BXD recombinant inbred mice: relationship to alcohol metabolism.

Studies were initiated to characterize behaviorally and biochemically C57BL/6J and DBA/2J inbred mice, as well as BXD Recombinant Inbred (RI) strains derived from them. The C57BL/6J, DBA/2J, and 7 BXD RI strains were tested for voluntary alcohol consumption (VAC) by receiving 4 days of forced exposure to a 10% (w/v) solution of alcohol, followed by 3 weeks of free choice between water and 10% alcohol. Measures of VAC included the absolute intake of alcohol (g/kg), as well as alcohol preference. A wide range of VAC was displayed by the various BXD RI strains with a continuous (rather than bimodal) distribution, indicating that there is likely to be additive effects of several genes involved in regulating alcohol-related behaviors. Kinetic characteristics of aldehyde dehydrogenase and catalase in liver and brain of the C57BL/6J, DBA/2J, and BXD strains of mice were determined to test the hypothesis that the genetic regulation of the levels of alcohol-metabolizing enzymes mediate differences in VAC. Aldehyde dehydrogenase activity was determined spectrophotometrically by observing the change in absorption at 340 nm. Catalase activity was determined by measuring oxygen production with a Yellow Springs Biological Oxygen monitor and oxygen electrode. There was a strong negative relationship between VAC and brain catalase activity in the BXD RI and parental strains. These data suggest that RI strains are likely to be useful genetic models in the examination of quantitative trait loci controlling VAC and other responses to alcohol.

Alcohol Drinking↗

PubMed1997

Role of gene conversion in generating polymorphisms at major histocompatibility complex loci.

Multigene families are known to be evolving under continued occurrence of unequal crossing-over and gene conversion, and MHC loci are no exceptions. Population genetic models of diversifying selection, with intra- and inter-locus gene conversion were studied by computer simulations. Weak selection at individual amino acid site is shown to be quite effective in enhancing polymorphisms, if gene conversion occurs. This is caused by the appearance of coadapted segments of mutations in which recombination tends to be suppressed. In addition to the global type of diversifying selection, endemic type of selection was introduced in some sets of simulations to find out a mechanism of the rapid allelic turnover of South American Indians. Strong selection is assumed such that the most common two alleles become lethal in one generation. If this endemic selection occurs periodically, allelic turnover by intralocus gene conversion is shown to become rapid. Hence, interaction of selection and gene conversion has a profound effect on MHC polymorphisms.

Alleles↗

PubMed1989

Role of gene duplication in evolution.

It is now known that many multigene and supergene families exist in eukaryote genomes: multigene families with uniform copy members like genes for ribosomal RNA, those with variable members like immunoglobulin genes, and supergene families such as those for various growth factor and hormone receptors. Many such examples indicate that gene duplication and subsequent differentiation are extremely important for organismal evolution. In particular, gene duplication could well have been the primary mechanism for the evolution of complexity in higher organisms. Population genetic models for the origin of gene families with diverse functions are presented, in which natural selection favors those genomes with more useful mutants in duplicated genes. Since any gene has a certain probability of degenerating by mutation, success versus failure in acquiring a new gene by duplication may be expressed as the ratio of probabilities of spreading of useful versus detrimental mutations in redundant gene copies. Also examined are the effects of gene duplication on evolution by compensatory advantageous mutations. Results of the analyses show that both natural selection and random drift are important for the origin of gene families. In addition, interaction between molecular mechanisms such as unequal crossing-over and gene conversion, and selection or drift is found to have a large effect on evolution by gene duplication.

Animals↗

PubMed2005

High-affinity peptide transporter PEPT2 (SLC15A2) of the zebrafish Danio rerio: functional properties, genomic organization, and expression analysis.

Solute carrier 15 (SLC15) membrane proteins PEPT1 (SLC15A1) and PEPT2 (SLC15A2) have been described in great detail in mammals. In contrast, information in lower vertebrates is limited. We characterized the functional properties of a novel zebrafish peptide transporter orthologous to mammalian and avian PEPT2, described its gene (pept2) structure, and determined mRNA tissue distribution. An expressed sequence tag (EST) cDNA (Integrated Molecular Analysis of Gene Expression; IMAGE) corresponding to zebrafish pept2 was completed by inserting a stretch of 75 missing nucleotides in the coding sequence to obtain a 3,238-bp functional clone. The complete open reading frame (ORF) was 2,160 bp and encoded a 719-amino acid protein. Electrophysiological analysis after cRNA injection in Xenopus laevis oocytes suggested that zebrafish PEPT2 is a high-affinity/low-capacity transporter (K(0.5) for glycyl-L-glutamine approximately 18 microM at -120 mV and pH 7.5). Zebrafish pept2 gene was 19,435 kb, thus being the shortest vertebrate pept2 fully characterized so far. Also, zebrafish pept2 exhibited 23 exons and 22 introns, whereas human and rodent pept2 genes contain 22 exons and 21 introns only. Zebrafish pept2 mRNA was mainly detected in brain, kidney, gut, and, interestingly, otic vesicle, the embryonic structure that develops into the auditory/vestibular organ, homolog to the higher vertebrate inner ear, of the adult fish. Characterization of zebrafish pept2 will contribute to the investigation of peptide transporters using a well-established genetic model and will allow the elucidation of the evolutionary and functional relationships among vertebrate peptide transporters. Moreover, it can represent a useful marker to screen mutations that affect choroid plexus and inner ear development.

Amino Acid Sequence↗

PubMed2002

Effect of mode of inheritance when calculating the power of a transmission/disequilibrium test study.

In assessing the power of an association study one needs to consider a variety of genetic models and to have some knowledge of the values of the relevant population parameters in those models. One's comparison of different models should be made such that these parameters are equal under each model. In practice one is most likely to have available estimates of the allele frequency (p) and of the relative risk to siblings of affected individuals (lambda(s)). In presenting power calculations for the transmission/disequilibrium test, previous authors have made comparisons of models which, while having the same gene frequency lead to completely different population outcomes, e.g. different values of lambda(s). Indeed, despite having the same values for their underlying parameters, these models do not necessarily provide the most useful comparison.

Chromosome Mapping↗

PubMed2003

Turning on the male--SRY, SOX9 and sex determination in mammals.

The decision of the bi-potential gonad to develop into either a testis or ovary is determined by the presence or absence of the Sex-determining Region gene on the Y chromosome (SRY). Since its discovery, almost 13 years ago, the molecular role that SRY plays in initiating the male sexual development cascade has proven difficult to ascertain. While biochemical studies of clinical mutants and mouse genetic models have helped in our understanding of SRY function, no direct downstream targets of SRY have yet been identified. There are, however, a number of other genes of equal importance in determining sexual phenotype, expressed before and after expression of SRY. Of these, one has proven of central importance to mammals and vertebrates, SOX9. This review describes our current knowledge of SRY and SOX9 structure and function in the light of recent key developments.

Animals↗

PubMedDate not supplied

Role of complex carbohydrates and neurulation.

Extracellular and cell-coat complex carbohydrates play a major role in critical cellular functions, e.g., cell recognition and cell-to-cell adherence, which are involved in neurulation. To date, available evidence suggests that neurulation is a combination of intercellular and extracellular biochemical and morphological events which are under the direction of the genome. To define the carbohydrate components that are essential to neurulation, normal C-57 and abnormal splotch (Sp/Sp) mouse embryos were studied using fluorescein-labeled lectins and computer-aided microspectrophotometric analysis of hyaluronate lyase and chondroitin ABC lyase-sensitive Alcian blue staining. Preliminary results of these studies indicate that the neuroepithelium of the splotch Sp/Sp mutant, a genetic model of a primary neural tube defect, is characterized by alterations in the type and amount of glycoconjugates and in the concentration of individual glycosaminoglycans. This review of mammalian neurulation discusses the importance of complex carbohydrates on the cell surface of the neuroepithelium of the closing neural fold.

Animals↗

PubMed1994

Genetic control of sex-chromosome inactivation during male meiosis.

During meiotic prophase in male mammals, the sex chromosomes are transcriptionally inactivated and form a condensed chromatin domain known as the sex body. It is not known how the assumption of this chromatin configuration is determined and regulated. We used various genetic models to test whether a complete sex-chromosome pair, effective sex-chromosome pairing, or an intact X chromosome is required for sex-body formation or transcription inactivation. The sex chromosome aberrations studied did not interfere with sex-body formation, and there is no evidence for inactivation failure or reactivation of the aberrant sex chromosomes. The results of this study suggest that control of sex-body formation is not intrinsic to the sex chromosomes and thus may be at the level of the testis.

Animals↗

PubMed1981

Exact significance levels of goodness-of-fit tests for the Hardy-Weinberg equilibrium.

The aim of this work is to examine the validity of several chi2 criteria, when used to test the fit of genotypic frequencies to the Hardy-Weinberg law. The exact type I error probabilities were compared to the nominal significance levels for two genetic models. The Pearson's chi2 test usually provided the best approximations. This test was found to be remarkably robust, when in situations involving very small expected frequencies.

ABO Blood-Group System↗

PubMed1982

Ascertainment bias for non-twin relatives in twin proband studies.

When families are ascertained through affected twins, as for example when twin probands are selected from a registry and their non-twin relatives studied, a correction for ascertainment bias is needed. It is shown that probandwise counting (where relatives of doubly ascertained twin pairs are counted twice) is the appropriate method. The bias resulting from pairwise counting is given and depends on the genetic model and on the probability of selecting an affected twin as a proband. For the multifactorial and generalized single major locus models the bias is small, and the problems associated with nonindependent ascertainment are negligible in practice.

Chromosome Mapping↗