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Results for “Genetic Variation”

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At least 73 records · Page 4Linked to original sources

PubMed2006

Murine weight loss exhibits significant genetic variation during dietary restriction.

We present genetic analyses of murine weight loss during dietary restriction (DR) for females eating 60% ad libitum (AL). We examined 5 cohorts across 81 different strains (22 strains tested twice) that included the LXS and LSXSS recombinant inbred strains, the LXS parental strains ILS and ISS, and the classical inbreds 129S6, A, BALB/c, C57BL/6, C3H, and DBA. Weight loss exhibited highly significant genetic variation, with DR body weights ranging from approximately 60 to approximately 85% of AL body weight. This variation was not explained by the strain differences in absolute food intake, feces calorie content, motor activity, or AL body fat. Heritability was 40-50%, and several provisional quantitative trait loci were mapped. This variation can be used to test whether weight loss correlates with the health benefits of DR, independently of the reduction in calories. The genetic variation also implies the existence of genes that would be novel therapeutic targets, distinct from genes affecting AL body weight or body fat, for enhancing (or mitigating) weight loss during food restriction.

Adipose Tissue↗

PubMed2001

A regression modeling approach for describing patterns of HIV genetic variation.

We introduce a novel approach for describing patterns of HIV genetic variation using regression modeling techniques. Parameters are defined for describing genetic variation within and between viral populations by generalizing Simpson's index of diversity. Regression models are specified for these variation parameters and the generalized estimating equation framework is used for estimating both the regression parameters and their corresponding variances. Conditions are described under which the usual asymptotic approximations to the distribution of the estimators are met. This approach provides a formal statistical framework for testing hypotheses regarding the changing patterns of HIV genetic variation over time within an infected patient. The application of these methods for testing biologically relevant hypotheses concerning HIV genetic variation is demonstrated in an example using sequence data from a subset of patients from the Multicenter AIDS Cohort Study.

Acquired Immunodeficiency Syndrome↗

PubMed2025

Investigating the interplay between prematurity and genetic variation in the context of rare developmental disorders.

BACKGROUND: Rare damaging genetic variation accounts for a substantial proportion of the risk of rare developmental disorders (DDs), but common genetic variants as well as environmental factors, including prematurity, also contribute. Little is known about the interplay between prematurity and genetic variation in influencing phenotypic outcomes in DDs, nor about how genetic factors may contribute to risk of preterm birth in DDs. METHODS: We leveraged phenotypic and genetic data from 21,712 patients with DDs recruited for clinical sequencing, 16% of whom were born prematurely. Using multivariable regression models, we compared phenotypic features and the prevalence of diagnostic genetic variation in specific genes between preterm and term individuals with DDs. We tested whether the fraction of cases attributable to de novo mutations differed between term and preterm probands. Additionally, we assessed whether associations between common variant contributions to education-related traits and prematurity are explained by direct genetic effects. RESULTS: Prematurity was associated with more severe clinical phenotypes among these DD patients, including more affected organ systems and more delayed developmental milestones. Prematurity and the presence of a monogenic diagnosis contributed additively to severity. We found that genes associated with fetal anomalies were enriched for diagnostic mutations among preterm individuals (p = 7.83 × 10-5). We also demonstrated an exome-wide enrichment of de novo mutations (DNMs) in both term and preterm probands; the fraction of cases explained by DNMs in known DD-associated genes was higher in term than preterm cases (25% versus 20%) but DNMs in as-yet-undiscovered genes likely contribute approximately equally to both groups (14% versus 13%). Finally, we showed that the positive association between polygenic predisposition to education-related traits and gestational duration is likely to be the result of genetically influenced parental traits or confounders, rather than direct genetic effects in the child, and that a monogenic diagnosis modifies this association. CONCLUSIONS: Our findings emphasise the importance of considering environmental factors like prematurity in understanding outcomes in DDs suspected to have a genetic component, and motivate further exploration of the role that genetic variation plays in influencing prematurity.

Humans↗

PubMed2004

Genetic variation in infestation with a directly transmitted ectoparasite.

Genetic variation in levels of parasitism of hosts is an underlying assumption of studies of coevolution, but few such estimates are available from the field. We studied genetic variation in the abundance of the chewing louse Hirundoecus malleus on its barn swallow host Hirundo rustica. These parasites are directly transmitted and a test of genetic variation of parasite abundance would thus provide a particularly strong test. The prevalence and the abundance of the chewing lice did not differ significantly between adult male and female hosts. The resemblance in parasite intensity of H. malleus of offspring and their parents was positive and highly significant, and an analysis of extra-pair paternity in the host allowed partitioning of this resemblance between genetic and common environment effects. There was no significant resemblance in parasite intensity between extra-pair offspring and their foster parents, although the resemblance remained for within-pair offspring. This provides evidence for the abundance of directly transmitted parasites having an additive genetic component. We found no evidence of common environment effects as parents did not resemble each other with respect to lice abundance.

Animals↗

PubMed2006

Genetic variation in Drosophila melanogaster pathogen susceptibility.

Genetic variation in susceptibility to pathogens is a central concern both to evolutionary and medical biologists, and for the implementation of biological control programmes. We have investigated the extent of such variation in Drosophila melanogaster, a major model organism for immunological research. We found that within populations, different Drosophila genotypes show wide-ranging variation in their ability to survive infection with the entomopathogenic fungus Beauveria bassiana. Furthermore, striking divergence in susceptibility has occurred between genotypes from temperate and tropical African locations. We hypothesize that this may have been driven by adaptation to local differences in pathogen exposure or host ecology. Genetic variation within populations may be maintained by temporal or spatial variation in the costs and benefits of pathogen defence. Insect pathogens are employed widely as biological control agents and entomopathogenic fungi are currently being developed for reducing malaria transmission by mosquitoes. Our data highlight the need for concern about resistance evolution to these novel biopesticides in vector populations.

Animals↗

PubMed2003

Extinction-colonization dynamics structure genetic variation of spotted sunfish (Lepomis punctatus) in the Florida Everglades.

The population genetics of aquatic animals in the Florida Everglades may be strongly influenced by extinction and colonization dynamics. We combined analyses of allozyme and microsatellite loci to test the hypothesis that two levels of population structure are present for spotted sunfish (Pisces: Centrarchidae: Lepomis punctatus) inhabiting the Everglades. We hypothesized that annual cycles of marsh dry-down increase local-scale genetic variation through a process of local extinction and colonization; we hypothesized that barriers to gene flow by levee/canal systems create a second, regional level of genetic variation. In 1996 and 1997, we sampled spotted sunfish from 11 Everglades sites that were distributed in three regions separated by levees. We documented patterns of genetic variation at 7 polymorphic allozyme loci and 5 polymorphic microsatellite loci. Most genetic variation was present among local populations, according to both types of genetic markers. Furthermore, samples from marsh sites were heterogeneous, while those from canals were not. These data supported our hypothesis that dry-down events and local population dynamics in the marsh have a significant effect on population genetic structure of spotted sunfish. We found no support for our hypothesis that water-management structures superimpose a second level of genetic structure on this species, possibly because canals obscure historical structure by facilitating gene flow or because the complete canal system has been in place for fewer than 20 generations of this species. Our data suggests a continent-island (canal-marsh) structure of populations with high gene flow among regions and recurrent mixing in marshes from canal and creek habitats.

Animals↗

PubMed2002

Effect of low stressful temperature on genetic variation of five quantitative traits in Drosophila melanogaster.

A half-sib analysis was used to investigate genetic variation for three morphological traits (thorax length, wing length and sternopleural bristle number) and two life-history traits (developmental time and larva-to-adult viability) in Drosophila melanogaster reared at a standard (25 degrees C) and a low stressful (13 degrees C) temperature. Both phenotypic and environmental variation showed a significant increase under stressful conditions in all traits. For estimates of genetic variation, no statistically significant differences were found between the two environments. Narrow heritabilities tended to be higher at 13 degrees C for sternopleural bristle number and viability and at 25 degrees C for wing length and developmental time, whereas thorax length did not show any trend. However, the pattern of genetic variances and evolvability indices (coefficient of genetic variation and evolvability), considered in the context of literature evidence, indicated the possibility of an increase in additive genetic variation for the morphological traits and viability and in nonadditive genetic variation for developmental time. The data suggest that the effect of stressful temperature may be trait-specific and this warns against generalizations about the behaviour of genetic variation under extreme conditions.

Analysis of Variance↗

PubMed1993

Genetic Variation within a Lotic Population of Janthinobacterium lividum.

An understanding of the genetic variation within and between populations should allow scientists to address many problems, including those associated with endangered species and the release of genetically modified organisms into the environment. With respect to microorganisms, the release of genetically engineered microorganisms is likely to increase dramatically given the current growth in the bioremediation industry. In this study, genetic variation within a lotic, bacterial population of Janthinobacterium lividum was measured with restriction fragment length polymorphism analysis. Chromosomal DNA from 10 Kettle Creek (Hawk Mountain Sanctuary, Kempton, Pa.) J. lividum isolates was digested with six restriction endonucleases and probed with a 7.5-kb pKK3535 fragment containing the E. coli rrnB rRNA operon. Genetic variation, as measured in terms of nucleotide diversity, was high within the population. The 0.0781 value for genetic variation was especially high given the conservative nature of the genetic probe. The average percent similarity among isolates within the population was 67.25%. Pairwise comparisons of nucleotide diversity values (pi) and similarity coefficients (F) yielded values ranging from 0.0032 to 0.1816 and 0.3363 to 0.9808, respectively. Putative clonemates were not present within the group of isolates; however, all isolates shared 14 fragments across a spectrum of six restriction enzymes. The presence of these common fragments indicates that restriction fragment length polymorphism analysis may provide population- or species-specific diagnostic markers for J. lividum. Data that suggest a plume effect with respect to the downstream movement of J. lividum are also presented. An increase in genetic variation within groups of isolates along the longitudinal gradient of Kettle Creek is also suggested.

Journal Article↗

PubMed2001

Genetic variation for preadult viability in Drosophila melanogaster.

The extent of genetic variation in fitness and its components and genetic variation's dependence on environmental conditions remain key issues in evolutionary biology. We present measurements of genetic variation in preadult viability in a laboratory-adapted population of Drosophila melanogaster, made at four different densities. By crossing flies heterozygous for a wild-type chromosome and one of two different balancers (TM1, TM2), we measure both heterozygous (TM1/+, TM2/+) and homozygous (+/+) viability relative to a standard genotype (TM1/TM2). Forty wild-type chromosomes were tested, of which 10 were chosen to be homozygous viable. The mean numbers produced varied significantly between chromosome lines, with an estimated between-line variance in log(e) numbers of 0.013. Relative viabilities also varied significantly across chromosome lines, with a variance in log(e) homozygous viability of 1.76 and of log(e) heterozygous viability of 0.165. The between-line variance for numbers emerging increased with density, from 0.009 at lowest density to 0.079 at highest. The genetic variance in relative viability increases with density, but not significantly. Overall, the effects of different chromosomes on relative viability were remarkably consistent across densities and across the two heterozygous genotypes (TM1, TM2). The 10 lines that carried homozygous viable wild-type chromosomes produced significantly more adults than the 30 lethal lines at low density and significantly fewer adults at the highest density. Similarly, there was a positive correlation between heterozygous viability and mean numbers at low density, but a negative correlation at high density.

Animals↗

PubMed1995

Lack of LTR and ENV genetic variation during bovine leukemia virus-induced leukemogenesis.

Genetic variation of the Bovine Leukemia Virus (BLV) appears to be limited in vitro and during the latent phase of the disease. However, cells in tumors often harbor deleted proviruses that are defective for expression. In order to gain insight into the involvement of viral genetic variation during pathogenesis, the BLV LTR and the env proviral sequences were analyzed in tumor tissues. A sheep (M230) was injected with the cloned BLV provirus 344 and became persistently infected with circulating lymphocytes reaching 345,000/mm3. After 11 months, this infected sheep developed leukemia-lymphoma. DNA was extracted from peripheral blood leukocytes at the time of tumor development and the LTR and the env gene were amplified, using the polymerase chain reaction procedure, cloned, and sequenced. Twenty independent LTR and twenty env clones were analyzed. It appeared that the in vivo mutation rate in the env gene was 0.043% (eight mutations including seven transitions out of 18,300 bp). Five point mutations (all transitions) were identified in the LTR, corresponding to 0.041% modifications (four mutations out of 9740 bp). These mutation rate values (0.043 and 0.041) were close to those due to the Taq DNA polymerase errors (0.030%). Altogether, these data demonstrate the lack of genetic variation in the LTR and the env gene during this case of BLV-induced pathogenesis in vivo. They confirm that the defectiveness of some BLV proviruses in vivo, thus, is not a mandatory step in the leukemogenic process.

Animals↗

PubMed2003

The stress-induced hsp12 gene shows genetic variation among Helicobacter pylori strains.

The transcriptional regulation, genetic variation and clinical relevance of the strain-specific hsp12 gene of the human gastric pathogen Helicobacter pylori were investigated. Although the transcription of the hsp12 gene in H. pylori strain 1061 was induced by growth under iron-, pH- and temperature-stress conditions, the gene was not essential for growth under these stress conditions. The locus containing the hsp12 gene showed considerable genetic variation. A total of eight different strain-specific alleles were identified, of which three are mosaic variants of the hsp12 gene and five that are unrelated to the hsp12 gene. The hsp12 locus of six paired sets of strains obtained from patients with 7-10-year time intervals remained unaltered, indicating that genetic variation does not occur during chronic infection. No significant association was found between the presence of a hsp12 gene and peptic ulcer disease in clinical isolates obtained from 26 patients. The stress-regulated, strain-specific hsp12 genes may be involved in adaptation of individual H. pylori strains to their specific hosts, and contribute to long-term colonization of the gastric niche.

Duodenal Ulcer↗

PubMed2005

Large-scale SNP analysis reveals clustered and continuous patterns of human genetic variation.

Understanding the distribution of human genetic variation is an important foundation for research into the genetics of common diseases. Some of the alleles that modify common disease risk are themselves likely to be common and, thus, amenable to identification using gene-association methods. A problem with this approach is that the large sample sizes required for sufficient statistical power to detect alleles with moderate effect make gene-association studies susceptible to false-positive findings as the result of population stratification. Such type I errors can be eliminated by using either family-based association tests or methods that sufficiently adjust for population stratification. These methods require the availability of genetic markers that can detect and, thus, control for sources of genetic stratification among populations. In an effort to investigate population stratification and identify appropriate marker panels, we have analysed 11,555 single nucleotide polymorphisms in 203 individuals from 12 diverse human populations. Individuals in each population cluster to the exclusion of individuals from other populations using two clustering methods. Higher-order branching and clustering of the populations are consistent with the geographic origins of populations and with previously published genetic analyses. These data provide a valuable resource for the definition of marker panels to detect and control for population stratification in population-based gene identification studies. Using three US resident populations (European-American, African-American and Puerto Rican), we demonstrate how such studies can proceed, quantifying proportional ancestry levels and detecting significant admixture structure in each of these populations.

Chromosomes, Human, X↗

PubMed2006

Inbreeding and reproduction in endangered ungulates: preservation of genetic variation through the Organization of Genetic Resource Banks.

There is a constant increase in the number of species suffering marked reductions in population size. This reduction in size and the lack of genetic flow may lead to a decrease in genetic variability and to matings between close relatives (i.e. inbreeding) with an ensuing reduction in fitness. It is thus important to understand the mechanism underlying the deleterious effects of inbreeding and to develop reproductive biotechnologies that will allow the reduction of inbreeding depression by facilitating gene exchange between populations. The study of three endangered species of gazelles, Cuvier's gazelle (Gazella cuvieri), Mohor gazelle (Gazella dama mhorr) and dorcas gazelle (Gazella dorcas neglecta) has revealed that inbreeding negatively affects several semen parameters (motility, sperm morphology, acrosome integrity). Semen cryopreservation has been achieved in the three species but success varies depending on the diluent employed and the level of inbreeding. Artificial insemination of Mohor gazelles have led to the birth of the first gazelle born using frozen-thawed semen but improvements are needed before this technology can be applied on a routine basis for the genetic management of the populations. Collection of oocytes after ovarian stimulation, followed by in vitro maturation, fertilization and culture has met with some initial success in the Mohor gazelle. These, together with other reproductive technologies, will offer an invaluable help in preserving the maximum of genetic diversity of these and related endangered ungulate species.

Animals↗

PubMed1975

Genetic variation in Nigeria. I. The genetics of phenylthiourea tasting ability.

Phenylthiourea (PTC) taste sensitivity thresholds have been measured for 2,013 Nigerians using a modified sorting technique. The frequency of non-tasters was observed to be 12.5% and the t gene frequency was 0.354. There was a significant difference between the sexes at the 0.01 level for the overall population. However, when the data are analyzed according to the geographical origin of the subject, the sex difference is found only in one of three geographical regions. Also, there may be geographical influences on PTC taste sensitivity, although this was not statistically significant. The estimates reported in this population differ considerably from some of the previously published estimates for black populations.

Adolescent↗

PubMed1983

Detection of genetic variation with radioactive ligands. V. Genetic variants of testosterone-binding globulin in human serum.

We examined genetically determined polymorphisms in testosterone-binding beta-globulin (TeBG) by polyacrylamide gel electrophoresis (PAGE). Four electrophoretic variants were identified, which we suggest are the result of combinations of three alleles. Gene frequencies were calculated for the three alleles in white American, black American, and Japanese-American populations. There was good agreement between observed and expected phenotype numbers. Distribution of phenotypes among offspring of several crosses was consistent with simple Mendelian inheritance of an autosomal gene.

Black or African American↗

PubMed2001

Genetic variation and clonal diversity in four clonal sedges (Carex) along the Arctic coast of Eurasia.

We studied the structure of genetic variation (at both ramet- and genet-level) and clonal diversity within and among populations in the four closely related arctic clonal sedges Carex bigelowii, C. ensifolia, C. lugens and C. stans by use of allozyme markers. Compared to other sedges and arctic plants, the studied taxa all had high levels of genetic variation, both within populations and taxa. These taxa contained most of the total gene diversity (H(T)) within populations and a small part of the diversity among populations (G(ST) ranged 0.05--0.43). Carex bigelowii had genetic variation (H(S) = 0.173, mean for populations) at a comparable level to other outbreeding arctic plants and to other widespread, rhizomatous and mainly outbreeding Carex species. In contrast, C. ensifolia (H(S) = 0.335), C. lugens (H(S) = 0.339) and C. stans (H(S) = 0.294) had within-population variations that were higher than in most other studied Carex species and for arctic plants in general. Genetic variation was not related to any tested environmental variable, but it was lower in areas deglaciated only 10,000 years BP compared to areas deglaciated 60,000 years BP or not glaciated at all during the Weichselian. All the populations were multiclonal, except for two populations of C. stans that were monoclonal. In contrast to genetic variation, clonal diversity decreased with latitude and did not differ between areas with different times of deglaciation. In accordance with previous studies, C. bigelowii and C. lugens were found to be outbreeding, while C. ensifolia and C. stans had mixed mating systems.

Arctic Regions↗

PubMed2000

Genetic variation: molecular mechanisms and impact on microbial evolution.

On the basis of established knowledge of microbial genetics one can distinguish three major natural strategies in the spontaneous generation of genetic variations in bacteria. These strategies are: (1) small local changes in the nucleotide sequence of the genome, (2) intragenomic reshuffling of segments of genomic sequences and (3) the acquisition of DNA sequences from another organism. The three general strategies differ in the quality of their contribution to microbial evolution. Besides a number of non-genetic factors, various specific gene products are involved in the generation of genetic variation and in the modulation of the frequency of genetic variation. The underlying genes are called evolution genes. They act for the benefit of the biological evolution of populations as opposed to the action of housekeeping genes and accessory genes which are for the benefit of individuals. Examples of evolution genes acting as variation generators are found in the transposition of mobile genetic elements and in so-called site-specific recombination systems. DNA repair systems and restriction-modification systems are examples of modulators of the frequency of genetic variation. The involvement of bacterial viruses and of plasmids in DNA reshuffling and in horizontal gene transfer is a hint for their evolutionary functions. Evolution genes are thought to undergo biological evolution themselves, but natural selection for their functions is indirect, at the level of populations, and is called second-order selection. In spite of an involvement of gene products in the generation of genetic variations, evolution genes do not programmatically direct evolution towards a specific goal. Rather, a steady interplay between natural selection and mixed populations of genetic variants gives microbial evolution its direction.

Bacteria↗

PubMed1999

Temporal changes in genetic variation of north European cattle breeds.

Temporal changes in genetic variation within and between 13 North European cattle breeds were evaluated using erythrocyte antigen systems and transferrin protein as genetic markers. Current data on allele frequency distributions of markers in large commercial and smaller endangered native cattle breeds were compared to data published during 1956 to 1975. Intrabreed genetic variation was quantified by conventional parameters (e.g. heterozygosity, average number of alleles per locus) and migration by the effective migration rate. The neighbour-joining dendrogram of relationships between old and present cattle populations was constructed using Nei's standard genetic distance. Variance effective population size was estimated from changes in allele frequencies over time. Comparison of old and new data indicated some significant changes in allele frequencies. In six of the breeds, a few low-frequency alleles in the old data were absent in the present samples. Heterozygosity remained stable in most breeds. The harmonic means for variance effective population size ranged between 30 and 257. Current results indicate that despite marked declines in total population sizes, North European native cattle breeds have retained a reasonably high genetic diversity. However, their genes contribute less than previously to genetic variation of Nordic production breeds. Commercial breeds do not appear to have a larger effective population size than native breeds. The present effective population sizes imply that Nordic breeds could have lost from 1 to 11% of their heterozygosity over a 20-40-year period.

Animals↗