[Immuno-epidemiological study of the natural variation of A and B viruses in Rumania during the past 30 years].
Explore the source record for details and available documents.
Humans↗
SEARCH · Search PubMed
Results for “Natural variation”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Basis for natural variation in sensitivity to 5-fluorouracil in mouse and human cells in culture.
Explore the source record for details and available documents.
Animals↗
Natural variation in neuron number in mice is linked to a major quantitative trait locus on Chr 11.
Common genetic polymorphisms-as opposed to rare mutations-generate almost all heritable differences in the size and structure of the CNS. Surprisingly, these normal variants have not previously been mapped or cloned in any vertebrate species. In a recent paper (), we suggested that much of the variation in retinal ganglion cell number in mice, and the striking bimodality of strain averages, are caused by one or two quantitative trait loci (QTLs). To test this idea, and to map genes linked to this variable and highly heritable quantitative trait, we have counted ganglion cells in 38 recombinant inbred strains (BXD and BXH) derived from parental strains that have high and low cell numbers. A genome-wide search using simple and composite interval-mapping techniques revealed a major QTL on chromosome (Chr) 11 in a 3 cM interval between Hoxb and Krt1 (LOD = 6.8; genome-wide p = 0.001) and possible subsidiary QTLs on Chr 2 and Chr 8. The Chr 11 locus, neuron number control 1 (Nnc1), accounts for one third of the genetic variance among BXH strains and more than half of that among BXD strains, but Nnc1 has no known effects on brain weight, eye weight, or total retinal cell number. Three strong candidate genes have been mapped previously to the same region as Nnc1. These genes-Rara, Thra, and Erbb2- encode receptors for retinoic acid, thyroxine, and neuregulin, respectively. Each receptor is expressed in the retina during development, and their ligands affect the proliferation or survival of retinal cells.
Animals↗
Statistical power in the detection of matrix effects.
Matrix-induced bias can adversely affect the performance evaluation a clinical laboratory receives on proficiency testing results. Therefore, it is vital that matrix effects from a matrix-biased system are detected and that laboratories using these systems are not falsely penalized on their proficiency testing results. The College of American Pathologists has developed an experimental protocol to test whether an observed bias is, in fact, due to the proficiency testing sample matrix rather than true performance or calibration problems. The probability of detecting a matrix effect using this protocol given a matrix-biased system is defined as statistical power. Five parameters are known to affect the probability of detection: (1) size of the bias in the proficiency testing material, (2) lack of fit coefficient of variation-natural variation in patient samples used to define the relationship between the test and reference methods, (3) pure error coefficient of variation-random variation in the test method, (4) the number of fresh patient samples, and (5) the number of replicates for each sample. The level of significance of the statistical test will also affect the probability of detection. Power curves are generated to show the effect these five parameters have on the determination of power. With the exception of bias, power is most influenced by the components of variance, lack of fit (nonlinear), and pure (random) error. Of these two components, the lack of fit error, which represents an uncontrollable source of error, is usually more influential than pure error, which can be reduced by a larger number of replicates. A large increase in power will result from an increase of fresh patient samples from 10 to 20, and a moderate increase in power will result from an increase of fresh patient samples from 20 to 40; no noticeable increase in power is seen with greater than 40 fresh patient samples. Large increases in power were observed for increases in the number of replicates per sample from one to two, two to three, and three to five. To markedly increase power further, 10 replicates would have to be assayed.
Bias↗
Quantitative variation in natural populations.
Quantitative variation is considered in natural populations using Drosophila as the example. A knowledge of such variation enables its rapid exploitation in directional selection experiments as shown for scutellar chaeta number. Where evidence has been obtained, genetic architectures are in qualitative agreement with Mather's concept of balance for traits under stabilizing selection. Additive genetic control is found for acute environmental stresses, but not for less acute stresses as shown by exposure to 60Co-gamma rays. D. simulans probably has a narrower ecological niche than its sibling species D. melanogaster associated with lower genetic heterogeneity. One specific environmental stress to which D. simulans is sensitive in nature is ethyl alcohol as shown by winery data.
Adaptation, Biological↗
Enhanced fitness conferred by naturally occurring variation in the circadian clock.
Natural variation in clock parameters is necessary for the circadian clock to contribute to organismal fitness over a broad geographic range. Considerable variation is evident in the period, phase, and amplitude of 150 Arabidopsis accessions, and the period length is correlated with the day length at the latitude of origin, implying the adaptive significance of correctly regulated circadian timing. Quantitative trait loci analysis of recombinant inbred lines indicates that multiple loci interact to determine period, phase, and amplitude. The loss-of-function analysis of each member of the ARABIDOPSIS PSEUDO-RESPONSE REGULATOR family suggests that they are candidates for clock quantitative trait loci.
Adaptation, Physiological↗
Mapping quantitative trait loci in multiple populations of Arabidopsis thaliana identifies natural allelic variation for trichome density.
The majority of biological traits are genetically complex. Mapping the quantitative trait loci (QTL) that determine these phenotypes is a powerful means for estimating many parameters of the genetic architecture for a trait and potentially identifying the genes responsible for natural variation. Typically, such experiments are conducted in a single mapping population and, therefore, have only the potential to reveal genomic regions that are polymorphic between the progenitors of the population. What remains unclear is how well the QTL identified in any one mapping experiment characterize the genetics that underlie natural variation in traits. Here we provide QTL mapping data for trichome density from four recombinant inbred mapping populations of Arabidopsis thaliana. By aligning the linkage maps for these four populations onto a common physical map, the results from each experiment were directly compared. Seven of the nine QTL identified are population specific while two were mapped in all four populations. Our results show that many lineage-specific alleles that either increase or decrease trichome density persist in natural populations and that most of this genetic variation is additive. More generally, these findings suggest that the use of multiple populations holds great promise for better understanding the genetic architecture of natural variation.
Arabidopsis↗
Naturally occurring variation in Arabidopsis: an underexploited resource for plant genetics.
The definition of gene functions requires the phenotypic characterization of genetic variants. Currently, such functional analysis of Arabidopsis genes is based largely on laboratory-induced mutants that are selected in forward and reverse genetic studies. An alternative complementary source of genetic variation is available: the naturally occurring variation among accessions. The multigenic nature of most of this variation has limited its application until now. However, the use of genetic methods developed to map quantitative trait loci, in combination with the characteristics and resources available for molecular biology in Arabidopsis, allow this variation to be exploited up to the molecular level. Here, we describe the current tools available for the forward genetic analysis of this variation, and review the recent progress in the detection and mapping of loci and the cloning of large-effect genes.
Arabidopsis↗
A comprehensive study of genic variation in natural populations of Drosophila melanogaster. IV. Mitochondrial DNA variation and the role of history vs. selection in the genetic structure of geographic populations.
Preliminary studies with restriction fragment length polymorphisms of mitochondrial DNA (mtDNA) in natural populations of Drosophila melanogaster revealed considerable variation in terms of nucleotide sequence and overall size. In this report we present data from more isofemale lines and more restriction enzymes, and explore the utility of the data in inferring a colonization history of this species. Size variation in the noncoding A + T-rich region is particularly plentiful, with size variants occurring in all restriction site haplotypes in all populations. We report here classes of small-scale mobility polymorphisms (apparent range of 20 bp) in specific restriction fragments in the coding region. The variation in one such fragment appears to be generated even more rapidly than in the noncoding region. On the basis of the distribution of restriction site haplotypes, the species range can be divided into three major regions along longitudinal lines: Euro-African populations are the most diverse and are taken to be oldest; Far East populations have a complex distribution of haplotypes; Western Hemisphere populations are the least diverse and are interpreted to be the youngest. The history inferred from mtDNA alone is remarkably similar to one based on several nuclear markers. The mtDNA haplotype distribution is also very different from that of allozymes in these same populations. We interpret this as further evidence that natural selection is still the most parsimonious explanation for the parallel latitudinal allozyme clines in this species.
Animals↗
From phenotypic to molecular polymorphisms involved in naturally occurring variation of plant development.
An enormous amount of naturally occurring genetic variation affecting development is found within wild and domesticated plant species. This diversity is presumably involved in plant adaptation to different natural environments or in human preferences. In addition, such intraspecific variation provides the basis for the evolution of plant development at larger evolutionary scales. Natural phenotypic differences are now amenable to genetic dissection up to the identification of causal DNA polymorphisms. Here we describe 30 genes and their functional nucleotide polymorphisms currently found as underlying allelic variation accounting for plant intraspecific developmental diversity. These studies provide molecular and cellular mechanisms that determine natural variation for quantitative and qualitative traits such as: fruit and seed morphology, colour and composition; flowering time; seedling emergence; plant architecture and inflorescence or flower morphology. Besides, analyses of flowering time variation within several distant species allow molecular comparisons between species, which are detecting homologous genes with partly different functions and unrelated genes with analogous functions. Thus, considerable gene function differences are being revealed also among species. Inspection of a catalogue of intraspecific nucleotide functional polymorphisms shows that transcriptional regulators are the main class of genes involved. Furthermore, barely more than half of the polymorphisms described are located in coding regions and affect protein structure, while the rest are regulatory changes altering gene expression. These limited analyses of intraspecific developmental variation support Doebley and Lukens's proposition (1998) that modifications in cis -regulatory regions of transcriptional regulators represent a predominant mode for the evolution of novel forms, but await more detailed studies in wild plant species.
Adaptation, Physiological↗
No evidence for an association between common nonsynonymous polymorphisms in delta and bristle number variation in natural and laboratory populations of Drosophila melanogaster.
We test the hypothesis that naturally occurring nonsynonymous variants in the Delta ligand of the Notch signaling pathway contribute to standing variation in sternopleural and/or abdominal bristle number in Drosophila melanogaster, for both a large cohort of wild-caught flies and previously described laboratory lines. We sequenced the transcribed region of Delta for 16 naturally occurring chromosomes and 65 SNPs, including 7 nonsynonymous SNPs (nsSNPs), were observed. Identified nsSNPs and 6 additional common SNPs, all located in exon 6 and the 3' UTR, were genotyped in 2060 wild-caught flies using an OLA-based methodology and genotyped in 38 additional natural chromosomes via DNA sequencing. None of the genotyped nsSNPs were significantly associated with natural variation in bristle number as assessed by a permutation test. A 95% upper bound on the additive genetic variance attributable to each genotyped SNP in the large natural cohort is <2% of the total phenotypic variation. Results suggest that two previously detected genotype/phenotype associations between bristle number and variants in the introns of Delta cannot be explained by linkage disequilibrium between these variants and nearby nonsynonymous variants. Unidentified regulatory variants more parsimoniously explain previous observations.
3' Untranslated Regions↗
Interactions between 2H and 18O natural abundance variations and DLW measurements of energy expenditure.
Appropriate corrections for 2H and 18O natural abundance are necessary in energy expenditure measurements with the doubly labeled water (DLW) method. The contribution of natural abundance variations to errors in the method is generally ignored if an appropriate dose level is given. Calculation of the appropriate dose level assumes that 2H and 18O natural abundance values are covariant and have a fixed slope. This study has investigated the between- and within-subject natural abundance variations, the latter over periods of time similar to those used in DLW experiment. Although 2H and 18O natural abundance values are covariant between subjects, the slope of their relationship is different from that of the Meteoric Water Line. Within subjects there is no such demonstrable covariance. It is concluded that: 1) the determinants of 2H and 18O natural abundance are different within and between subjects; 2) the concept of an optimal ratio of doses is not valid, and a safer strategy is probably to use a ratio > 10; 3) natural abundance variations may contribute significantly to the magnitude of error in the DLW measurements of energy expenditure.
Deuterium↗
Distribution of chromosome length variation in natural isolates of Escherichia coli.
Large-scale variation in chromosome size was analyzed in 35 natural isolates of Escherichia coli by physical mapping with a restriction enzyme whose sites are restricted to rDNA operons. Although the genetic maps and chromosome lengths of the laboratory strains E. coli K12 and Salmonella enterica sv. Typhimurium LT2 are highly congruent, chromosome lengths among natural strains of E. coli can differ by as much as 1 Mb, ranging from 4.5 to 5.5 Mb in length. This variation has been generated by multiple changes dispersed throughout the genome, and these alterations are correlated; i.e., additions to one portion of the chromosome are often accompanied by additions to other chromosomal regions. This pattern of variation is most probably the result of selection acting to maintain equal distances between the replication origin and terminus on each side of the circular chromosome. There is a large phylogenetic component to the observed size variation: natural isolates from certain subgroups of E. coli have consistently larger chromosome, suggesting that much of the additional DNA in larger chromosomes is shared through common ancestry. There is no significant correlation between genome sizes and growth rates, which counters the view that the streamlining of bacterial genomes is a response to selection for faster growth rates in natural populations.
Chromosome Mapping↗
Natural human tumor necrosis factor beta (lymphotoxin). Variable O-glycosylation at Thr7, proteolytic processing, and allelic variation.
Natural human tumor necrosis factor beta (TNF-beta) purified from supernatants of a human B-lymphoblastoid cell line was found to be heterogeneous in molecular mass, with seven components resolved by gel electrophoresis. All components are N-glycosylated at Asn62; N-glycosylation does not contribute to heterogeneity. In addition, part of the molecules are O-glycosylated at Thr7; O-glycosylation is heterogeneous due to variable decoration with neuraminic acid. The four lower molecular mass forms are derived from the full-length protein by trypsin-like proteolytic cleavage in the N-proximal region; these clipped molecules lack O-linked carbohydrates. Two allelic variants differing in amino acid position 26 (threonine/asparagine) were identified.
Alleles↗
Precision of DLW energy expenditure measurements: contribution of natural abundance variations.
Accuracy and precision of the the doubly labeled water (DLW) measurements of energy expenditure are commonly estimated with models that do not account for 2H and 18O natural abundance variation. A new and simple treatment that completes the ratio-product model is derived in the present study. It uses both linear regression of multipoint data with time and information on within-subject 2H and 18O natural abundance variation. Use of this treatment is demonstrated in a group of seven subjects in whom 2H and 18O natural abundance variation was assessed by collecting predose samples for 6-8 days before dosing. In this set of 16 measurements, the precision (coefficient of variation) of individual DLW estimates of CO2 production was 4.90 +/- 2.14%, of which 3.23 +/- 1.20% arose from natural abundance variation.
Adult↗
Natural genetic variation for improving crop quality.
The narrow genetic basis of many crops combined with restrictions on the commercial use of genetically modified plants, has led to a surge of interest in exploring natural biodiversity as a source of novel alleles to improve the productivity, adaptation, quality and nutritional value of crops. Genetic methodologies have been applied to natural variation to improve quality aspects that are associated with the chemical composition of agricultural products. A future challenge in this emerging field is to integrate metabolic, phenotypic and genomic databases to allow a wider view of the plant metabolome and the application of this knowledge within genomics-assisted breeding.
Biodiversity↗
Heat-responsive ONSEN long terminal repeats integrate heat shock factor motifs, DNA methylation and natural sequence variation in Arabidopsis.
ONSEN is a heat-activated Ty1/copia retrotransposon in Arabidopsis thaliana controlled by heat shock factors (HSFs) and epigenetic silencing. Heat shock element (HSE)-like sequences in ONSEN long terminal repeats (LTRs) contribute to heat responsiveness, but relationships among sequence architecture, basal DNA methylation and natural variation remain unclear. We combined transcription-factor motif prediction, transposable-element comparisons, methylome and RNA sequencing (RNA-seq) data, and Arabidopsis genome assemblies. In silico disruption of five HSE cores eliminated HSF-family motif compatibility in the selected design and all 5119 exact-guanine-cytosine (GC) alternatives. Across 16 curated Columbia-0 terminal windows, ONSEN contained 33-49 non-redundant HSF motif-coordinate placements per 800 bp window and was strongly enriched relative to 1930 non-ONSEN transposable elements across score thresholds and continuous metrics. Direct comparison with 779 non-ONSEN LTR retrotransposons showed selectively elevated basal CHH methylation (where H = A, C or T) at ONSEN termini. Genome-wide RNA-seq analysis revealed broad heat-responsive gene and transposable-element changes, including strong ONSEN induction, whereas candidate-window analysis distinguished ONSEN from most HSF-rich non-ONSEN outliers. ONSEN-like variants across eight accessions generally retained HSF-compatible motifs while altering predicted DNA binding with one finger-family motif composition. Together, these findings define ONSEN terminal regions as HSF-rich regulatory sequences that retain heat-responsive potential within a methylated chromatin context and identify candidates for functional analysis.
DNA Methylation↗
Sequence-tagged-site (STS) markers of arbitrary genes: the amount and nature of variation revealed in Norway spruce.
We examined the amount and nature of variation revealed by cDNA-based sequence-tagged-site (STS) markers in Norway spruce (Picea abies (L.) Karst.) using 39 pairs of heterologous primers that were based upon arbitrary genes in black spruce (Picea mariana (Mill.) B.S.P.). A panel of 22 diverse Norway spruce genotypes was screened for variation that could be observed directly using standard agarose gel electrophoresis, without additional manipulation of amplification products. Examination of marker segregation among haploid megagametophytes revealed that nine markers behaved in a codominant manner, two markers had codominant length polymorphisms and null alleles, and four others had dominant length polymorphisms. DNA sequencing of codominant alleles at seven loci indicated that most insertions/deletions (indels) were in noncoding regions and that alleles often differed by the presence or absence of direct repeats that ranged in size from three to 23 bp. The nine markers that showed exclusively codominant polymorphisms in Norway spruce had an average observed heterozygosity of 0.30 and an average of 2.9 alleles in the panel of 22 trees. These levels of variation are similar to those previously found for similar sets of markers in other spruces, and appear to be at least as high as those revealed by polymorphic allozyme markers in Norway spruce. Polymorphisms at one STS locus suggested a higher affinity between Norway spruce and white spruce (Picea glauca (Moench) Voss) than between either of these spruces and black spruce. The STS markers described in this report should be useful in a variety of applications in Norway spruce, including population studies and genome mapping.
Base Sequence↗