SEARCH · PubMed Health

Results for “variational inference”

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

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

At least 523 records · Page 29Linked to original sources

PubMed2002

Sequence divergence of rice microsatellites in Oryza and other plant species.

To determine the basis of genetic variation at microsatellite loci, eleven primer pairs, developed to amplify microsatellite markers in rice, were evaluated for their ability to amplify a PCR product and for both electromorphic and sequence-based polymorphism of the resulting products in 12 plant samples, including representatives from six different species within the genus Oryza and one genotype each from Zea (maize), Triticum (wheat) and Arabidopsis. PCR amplification was reliable in the four O. sativa samples as well as in the closely related Oryza relatives with AA genomes, while only 73% (8/11) of primers amplified in the BB/CC and CC genomes of Oryza, and 27% (3/11) amplified in the other genera. Three out of seven DNA fragments that were amplified from all genera were determined to be orthologous to their rice counterparts. A total of 115 amplicons were detected using polyacrylamide gel electrophoresis and these clustered into 74 distinct electromorphs. Sequencing of 108 amplicons revealed size homoplasy, exposing 13 new sequence-based variants. Allelic diversity within a species was predominantly due to changes in the number of repeats in the microsatellite region, but the frequency of insertions/deletions (indels) and base substitutions increased as the genetic distance between samples increased. This study suggests that electromorph size polymorphism is an adequate measure of genetic difference in studies involving closely-related individuals, but that when phylogenetic or evolutionary inferences are being made over longer time scales, evaluation of SSR variation at the sequence level is essential.

Base Sequence↗

PubMed1998

The correlation of protein structure and evolution of a protein-coding gene: phylogenetic inference using cytochrome oxidase III.

Discriminating phylogenetic signal from noise in DNA sequence data is a difficult problem in phylogenetic inference at higher systematic levels. For protein-coding genes, noise at synonymous (silent) positions can be filtered by deleting entire codon positions or types of change at a codon position. This method is not appropriate for replacement sites, because changes at each site within a codon may not be independent. This research presents a method using information from protein structure to evaluate variation in replacement sites. Analysis of the correlation of amino acid variation with protein structure identified rapidly evolving codons in the COIII gene. In a series of phylogenetic analyses attempting to recover a known set of vertebrate relationships, downweighting these labile codons produced the most accurate results. Structural correlates of variable and invariant residues identified in this study can be used to increase the accuracy of models used for phylogenetic inference. Viewing amino acid variation within a phylogenetic framework provided insight into residue changes important in the secondary and tertiary structures of the molecule, changes that were correlated between pairs of neighboring residues or between residues in neighboring helices.

Amino Acid Substitution↗

PubMed2002

Microsatellite variability in peach [ Prunus persica (L.) Batsch]: cultivar identification, marker mutation, pedigree inferences and population structure.

A collection of 212 peach and nectarine cultivars covering a wide variation of the species were studied with 16 polymorphic single-locus microsatellite, or simple-sequence repeat (SSR), markers. The average number of alleles per locus was 7.3, 35% of the cultivar x locus combinations analyzed were heterozygous and 87% of the cultivars studied could be individually identified. Most of the groups where two or more cultivars had the same SSR fingerprint included known peach mutants or possible synonymies. Pedigree information was tested with the SSR data. Five unexpected genotypes, due to a mutation at five SSR loci were found when comparing the SSR fingerprint of 14 known mutant cultivars and putative synonymous cultivars. The pedigree data were not consistent with the observed data in 11 out of 38 cases that could be analyzed. The group of non-melting fruit flesh cultivars, generally used by the canning industry, was more variable and genetically distant than the rest of the cultivars tested. Based on their level of homozygosity it was possible to separate those cultivars that were obtained by modern breeding technologies from those that were selected from traditional orchards after generations of seed propagation. The former had a distribution of genotypic frequencies close to a random mating model while the latter had a higher level of homozygosity. The implications of these data for the use of SSR fingerprints in breeder's rights protection and peach breeding are discussed.

Heterozygote↗

PubMed2006

A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase.

We present a statistical model for patterns of genetic variation in samples of unrelated individuals from natural populations. This model is based on the idea that, over short regions, haplotypes in a population tend to cluster into groups of similar haplotypes. To capture the fact that, because of recombination, this clustering tends to be local in nature, our model allows cluster memberships to change continuously along the chromosome according to a hidden Markov model. This approach is flexible, allowing for both "block-like" patterns of linkage disequilibrium (LD) and gradual decline in LD with distance. The resulting model is also fast and, as a result, is practicable for large data sets (e.g., thousands of individuals typed at hundreds of thousands of markers). We illustrate the utility of the model by applying it to dense single-nucleotide-polymorphism genotype data for the tasks of imputing missing genotypes and estimating haplotypic phase. For imputing missing genotypes, methods based on this model are as accurate or more accurate than existing methods. For haplotype estimation, the point estimates are slightly less accurate than those from the best existing methods (e.g., for unrelated Centre d'Etude du Polymorphisme Humain individuals from the HapMap project, switch error was 0.055 for our method vs. 0.051 for PHASE) but require a small fraction of the computational cost. In addition, we demonstrate that the model accurately reflects uncertainty in its estimates, in that probabilities computed using the model are approximately well calibrated. The methods described in this article are implemented in a software package, fastPHASE, which is available from the Stephens Lab Web site.

Calibration↗

PubMed2000

Molecular-functional studies of adaptive genetic variation in prokaryotes and eukaryotes.

Knowledge of both prokaryotic and eukaryotic organisms is essential to the study of molecular evolution. Their common ancestry mandates that their molecular functions share many aspects of adaptation and constraint, yet their differences in size, ploidy, and structural complexity also give rise to divergent evolutionary options. We explore the interplay of adaptation, constraint, and neutrality in their evolution by the use of genetic variants to probe molecular function in context of molecular structure, metabolic organization, and phenotype-environment interactions. Case studies ranging from bacteria to butterflies, flies, and vertebrates emphasize, among other points: the importance of moving from initial recording of evolutionary pattern variation to studying the processes underlying the patterns, by experiment, reconstructive inference, or both; the complementarity, not conflict, of finding different performance and fitness impacts of natural variants in prokaryotes or eukaryotes, depending on the nature and magnitude of the variants, their locations and roles in pathways, the nature of molecular function affected, and the resulting organismal phenotype-environment interactions leading to selection or its absence; the importance of adaptive functional interaction of different kinds of variants, as in gene expression variants versus variants altering polypeptide properties, or interaction of changes in enzymes' active sites with complementary changes elsewhere that adjust catalytic function in different ways, or coadaptation of different steps' properties in pathways; the power afforded by combining structural and functional analyses of variants with study of the variants' phenotype-environment interactions to understand how molecular changes affect (or fail to affect) adaptive mechanisms "in the wild." Comparative study of prokaryotes and eukaryotes in this multifaceted way promises to deliver both new insights into evolution and a host of new and productive questions about it.

Adaptation, Physiological↗

PubMed1998

The molecular basis of quantitative genetic variation in central and secondary metabolism in Arabidopsis.

To find the genes controlling quantitative variation, we need model systems where functional information on physiology, development, and gene regulation can guide evolutionary inferences. We mapped quantitative trait loci (QTLs) influencing quantitative levels of enzyme activity in primary and secondary metabolism in Arabidopsis. All 10 enzymes showed highly significant quantitative genetic variation. Strong positive genetic correlations were found among activity levels of 5 glycolytic enzymes, PGI, PGM, GPD, FBP, and G6P, suggesting that enzymes with closely related metabolic functions are coregulated. Significant QTLs were found influencing activity of most enzymes. Some enzyme activity QTLs mapped very close to known enzyme-encoding loci (e.g., hexokinase, PGI, and PGM). A hexokinase QTL is attributable to cis-acting regulatory variation at the AtHXK1 locus or a closely linked regulatory locus, rather than polypeptide sequence differences. We also found a QTL on chromosome IV that may be a joint regulator of GPD, PGI, and G6P activity. In addition, a QTL affecting PGM activity maps within 700 kb of the PGM-encoding locus. This QTL is predicted to alter starch biosynthesis by 3.4%, corresponding with theoretical models, suggesting that QTLs reflect pleiotropic effects of mutant alleles.

Analysis of Variance↗

PubMed2025

A General Framework for Branch Length Estimation in Ancestral Recombination Graphs.

Inference of Ancestral Recombination Graphs (ARGs) is of central interest in the analysis of genomic variation. ARGs can be specified in terms of topologies and coalescence times. The coalescence times are usually estimated using an informative prior derived from coalescent theory, but this may generate biased estimates and can also complicate downstream inferences based on ARGs. Here we introduce, POLEGON, a novel approach for estimating branch lengths for ARGs which uses an uninformative prior. Using extensive simulations, we show that this method provides improved estimates of coalescence times and lead to more accurate inferences of effective population sizes under a wide range of demographic assumptions (population expansion, bottleneck, split, etc). It also improves other downstream inferences including estimates of mutation rates. We apply the method to data from the 1000 Genomes Project to investigate population size histories and differential mutation signatures across populations. We also estimate coalescence times in the HLA region, and show that they exceed 30 million years in multiple segments.

Ancestral Recombination Graph↗

PubMed2001

Multilocus nested haplotype networks extended with DNA fingerprints show common origin and fine-scale, ongoing genetic divergence in a wild microbial metapopulation.

Nested haplotype networks for three loci in a haploid, fungal plant pathogen, Sclerotinia sclerotiorum, in two natural, Norwegian populations of the woodland buttercup, Ranunculus ficaria, were extended with DNA fingerprints to determine fine-scale population divergence. To preserve the cladistic structure in the network for both nonrecombinant and postrecombinant haplotypes in highly recombinant clades, recombinant events were not removed ('peeled off'), but instead were examined in alternative (marginal) networks. Fungi from both sampling locations share a common origin with subsequent genetic divergence, consistent with expectations for metapopulation structure. Evidence for divergence includes (i) lack of shared fingerprints between the two locations, (ii) evolution of new fingerprints, via transposition and recombination, within 2 years on a fine spatial scale within one sampling location, and (iii) increase in the size of the intergenic spacer (IGS) in both sampling locations. Sites of microsatellite repeat expansion and of an insertion were consistent with the boundaries of two recombination blocks in the IGS. Both alternative networks based on the recombination blocks were essential to finding all associations of DNA fingerprints with IGS size, sampling site, sampling year and mycelial compatibility group. Variation in the elongation factor 1alpha and calmodulin loci supported the topologies and the recurrent, ongoing polarity of change in fingerprints and IGS size inferred from the IGS.

Ascomycota↗

PubMed2004

Phylogeography, genetic structure and diversity in the endangered bearded vulture (Gypaetus barbatus, L) as revealed by mitochondrial DNA.

Bearded vulture populations in the Western Palearctic have experienced a severe decline during the last two centuries that has led to the near extinction of the species in Europe. In this study we analyse the sequence variation at the mitochondrial control region throughout the species range to infer its recent evolutionary history and to evaluate the current genetic status of the species. This study became possible through the extensive use of museum specimens to study populations now extinct. Phylogenetic analysis revealed the existence of two divergent mitochondrial lineages, lineage A occurring mainly in Western European populations and lineage B in African, Eastern European and Central Asian populations. The relative frequencies of haplotypes belonging to each lineage in the different populations show a steep East-West clinal distribution with maximal mixture of the two lineages in the Alps and Greece populations. A genealogical signature for population growth was found for lineage B, but not for lineage A; futhermore the Clade B haplotypes in western populations and clade A haplo-types in eastern populations are recently derived, as revealed by their peripheral location in median-joining haplotype networks. This phylogeographical pattern suggests allopatric differentiation of the two lineages in separate Mediterranean and African or Asian glacial refugia, followed by range expansion from the latter leading to two secondary contact suture zones in Central Europe and North Africa. High levels of among-population differentiation were observed, although these were not correlated with geographical distance. Due to the marked genetic structure, extinction of Central European populations in the last century re-sulted in the loss of a major portion of the genetic diversity of the species. We also found direct evidence for the effect of drift altering the genetic composition of the remnant Pyrenean population after the demographic bottleneck of the last century. Our results argue for the management of the species as a single population, given the apparent ecological exchangeability of extant stocks, and support the ongoing reintroduction of mixed ancestry birds in the Alps and planned reintroductions in Southern Spain.

Africa↗

PubMed2026

Can't see the forest for the trees: The influence of marker type on inferred phylogenetic relationships in a cosmopolitan bat genus.

Fine-resolution information on species relationships and biological diversity is critically needed to guide conservation efforts amidst rapid environmental changes. Systematics, which forms the foundation of this knowledge, has been revolutionized by phylogenomics, utilizing genome-scale datasets. However, the use of diverse marker types, non-comparable taxon sampling, and outgroup selection can lead to conflicting phylogenetic hypotheses. These inconsistencies complicate study comparisons and hinder our ability to assess marker-specific impacts on phylogenetic resolution. The phylogenetic reconstruction of the bat genus Myotis, encompassing over 140 species and characterized by a rapid radiation in the last 20 million years, has been particularly influenced by these challenges. Achieving phylogenetic resolution in Myotis is particularly complex due to subtle interspecific differences in both morphological and molecular traits. Mitochondrial and nuclear markers often produce discordant trees, influenced by hybridization, introgression, and methodological variations. In this study, we employed a consistent taxonomic sample set of 44 Myotis taxa to evaluate the impact of five different genetic marker types on phylogenetic reconstruction. We observed significant discordance between topologies derived from conserved nuclear and mitochondrial markers and found that transposable elements were inadequate for resolving relationships across the entire genus. Our results also clarify the placement of previously problematic taxa within the genus. These findings emphasize the importance of aligning genetic marker choice with specific phylogenetic questions and highlight the influence of taxonomic and methodological variation on phylogenomic outcomes. This work provides a framework for improving phylogenetic inference in rapidly radiating groups and enhances our understanding of evolutionary history in Myotis.

Animals↗

PubMed2026

An archaic reference-free method to jointly infer Neanderthal and Denisovan introgressed segments in modern human genomes.

Admixture between populations is a common feature of human history. Admixture events introduce new genetic variation that can fuel evolution. Characterizing the significance of admixture events on the evolution of populations across various species is of great interest to evolutionary geneticists. Local Ancestry Inference (LAI) methods infer genetic ancestry of an individual at a particular chromosomal location. Certain methods specialize in detecting archaic introgression, which consists of interbreeding between modern and archaic humans like Neanderthals and Denisovans. Most current LAI methods allow the detection of a single archaic ancestry, and post-processing may distinguish between multiple waves of introgression. These methods vary in how they choose archaic or modern reference genomes for the inference. Here, we present a new HMM-based method (DAIseg), which has the advantage of simultaneously distinguishing between multiple waves of ancient and recent admixture, using only modern human reference genomes. Simulations demonstrate that DAIseg achieves higher overall performance than state-of-the-art methods. We also apply DAIseg to Papuan populations to jointly detect Denisovan and Neanderthal introgressed segments, and identify a higher number of archaic segments than previous methods. Analysis of inferred introgressed segments, shows that we can identify evidence for two Denisovan introgression events in Papuans. Overall, on top of being able to deal with both Archaic and recent admixture, DAIseg provides a more principled approach for detecting and classifying Denisovan and Neanderthal segments which will improve downstream analysis of introgressed segments to infer the impact of archaic introgression in humans.

Denisovan↗

PubMed1990

Spectral resolution of cardio-circulatory variations in men measured by autorhythmometry over 2 years.

An analogue of the periodogram method for unequally spaced data is presented with a view to resolving the frequency structure of the observations. The algorithm is explicitly based on the sequential least squares procedure. In particular, the key concept is that the within-plot spectral analysis can be augmented by the between-plot information to make inferences about common characteristics. It is also shown how the between-plot random variations can be incorporated into the multiple harmonic regression model. A detailed spectral analysis investigates the periodic fluctuations in four cardio-circulatory variables, measured by autorhythmometric observation by eight men at rest and extending over a time span of 2 years. The spectral curves show the existence of circadian and circaseptan rhythmicities. The amplitude modulation of the dian rhythm by circaseptan variation is assimilated with the rhythmicity of work during the week. The blood-pressure variables situate their maximum annual peak in the winter period. These quasi-periodic fluctuations appear to be related to the amount of physical activity performed in time by the subjects.

Adult↗

PubMed1997

Genetic evidence of widespread dispersal in a parthenogenetic freshwater ostracod.

We used an hierarchical analysis of allozyme variation to investigate for the freshwater ostracod Candonocypris novaezelandiae the relative contributions of sexual and asexual reproduction to recruitment into 42 local populations and to infer patterns of gene flow within and among four geographical regions (watersheds) in south-eastern Australia. Allele frequency variation among local populations was marked (mean F(ST)=0.228) but showed no regional differentiation. The allele frequency differences among local populations probably reflect the effects of stochastic processes, such as founder events, as well as variation in the success, and hence abundance, of particular clonal genotypes within water-bodies. Indeed, local populations were highly clonal, containing only females and displaying relatively low levels of genotypic diversity. Nevertheless, the distribution of genotypes within and among regions was surprising. The bulk of sampled individuals (88 per cent) were represented by just six common genotypes that were shared extensively among local populations and were geographically widespread. Individual samples contained a mean of 4.05, and up to 10, distinct four-locus genotypes and overall we detected a total of 26 electrophoretically distinct genotypes. In combination, our results suggest that either the south-eastern Australian populations of C. novaezelandiae arose through a recent colonization event (perhaps associated with an expansion of agricultural practices) or there is sufficient continuing gene flow between regions to prevent differentiation. However, the exact contributions of sexual and asexual reproduction to dispersal in this ostracod remain unclear.

Journal Article↗

PubMed1979

The regularity of muscle spindle discharge in man.

1. The variability of discharge of thirty-nine muscle spindle afferents from the pretibial muscles of normal human subjects was determined for spike train sequences recorded with the ankle joint fixed in 25 degrees plantar flexion, during further stretch and during graded voluntary contractions of the receptor-bearing muscle. 2. In non-contracting muscles with the ankle joint in 25 degrees plantar flexion, a sustained discharge was maintained by twenty-four of the thirty-nine endings. The mean discharge frequency for the active endings was 11.1 Hz (range 4.8--22.1 Hz), the mean coefficient of variation 0.073 (range 0.021--0.183). With further stretch, the discharge of endings maintaining frequencies below 10--12 Hz became more regular. For endings maintaining higher frequencies, changes in the coefficient of variation were small and occurred in either direction. All secondary endings maintained a highly regular discharge, but, at these frequencies, there was no statistically significant difference in the variability of primary and secondary endings. 3. It is considered that these findings are comparable to those of Matthews & Stein (1969) for de-efferented feline spindle endings, and support the view that there is no functionally effective background fusimotor drive to non-contracting muscles of normal human subjects. 4. A voluntary contraction sufficient to accelerate a spindle ending invariably decreased the regularity of its afferent discharge. During voluntary contractions, coefficients of variation up to 0.345 were recorded. However, coefficients as low as 0.1 were not uncommon, and thus the absence of fusimotor drive cannot necessarily be inferred from a regular afferent discharge pattern. 5. With contractions of different strength, the increase in the coefficient of variation did not parallel the increase in discharge frequency. It is concluded that not all fusimotor influences acting on a spindle ending are translated into variability, and that measurements of the variability of discharge do not accurately reflect the level of fusimotor drive. 6. The discharge frequency of some spindle endings decreased slightly in some contractions and this was accompanied by an increase in the variability of discharge. It is suggested that contracting extrafusal muscle fibres can modulate the discharge pattern of spindle endings and contribute to the variability of discharge during a voluntary contraction. 7. In contracting muscles the irregular fusimotor-driven spindle discharge contained a 'hidden' periodicity, but this was not as extensive as has been reported for the cat. No such periodicity could be demonstrated for spindle endings in non-contracting human muscles.

Action Potentials↗

PubMed2001

Shared nucleotide composition biases among species and their impact on phylogenetic reconstructions of the Drosophilidae.

Compositional changes are a major feature of genome evolution. Overlooking nucleotide composition differences among sequences can seriously mislead phylogenetic reconstructions. Large compositional variation exists among the members of the family Drosophilidae. Until now, however, base composition differences have been largely neglected in the formulations of the nucleotide substitution process used to reconstruct the phylogeny of this important group of species. The present study adopts a maximum-likelihood framework of phylogenetic inference in order to analyze five nuclear gene regions and shows that (1) the pattern of compositional variation in the Drosophilidae does not match the phylogeny of the species; (2) accounting for the heterogeneous GC content with Galtier and Gouy's nucleotide substitution model leads to a tree that differs in significant aspects from the tree inferred when the nucleotide composition differences are ignored, even though both phylogenetic hypotheses attain strong nodal support in the bootstrap analyses; and (3) the LogDet distance correction cannot completely overcome the distorting effects of the compositional variation that exists among the species of the Drosophilidae. Our analyses confidently place the Chymomyza genus as an outgroup closer than the genus Scaptodrosophila to the Drosophila genus and conclusively support the monophyly of the Sophophora subgenus.

Alcohol Dehydrogenase↗

PubMed1998

An evaluation of RAPD fragment reproducibility and nature.

Random amplified polymorphic DNA (RAPD) fragment reproducibility was assayed in three animal species: red deer (Cervus elaphus), wild boar (Sus scrofa) and fruit fly (Drosophila melanogaster). Ten 10-mer primers (Operon) were tested in two replicate reactions per individual under different stringency conditions (annealing temperatures of 35 degrees C or 45 degrees C). Two estimates were generated from the data: autosimilarity, which tests the reproducibility of overall banding patterns, and band repeatability, which tests the reproducibility of specific bands. Autosimilarity (the similarity of individuals with themselves) was lower than 1 for all three species ranging between values of 0.66 for Drosophila at 45 degrees C and 0.88 for wild boar at 35 degrees C. Band repeatability was estimated as the proportion of individuals showing homologous bands in both replicates. The fraction of repeatable bands was 23% for deer, 36% for boar and 26% for fruit fly, all at an annealing temperature of 35 degrees C. Raising the annealing temperature did not improve repeatability. Phage lambda DNA was subjected to amplification and the pattern of bands compared with theoretical expectations based on nucleotide sequence. Observed fragments could not be related to expected ones, even if a 2 bp mismatch is allowed. Therefore, the nature of genetic variation uncovered by the RAPD method is unclear. These data demonstrate that prudence should guide inferences about population structure and nucleotide divergence based on RAPD markers.

Animals↗

PubMed2000

Marker-inferred relatedness as a tool for detecting heritability in nature.

This paper presents a perspective of how inferred relatedness, based on genetic marker data such as microsatellites or amplified fragment length polymorphisms (AFLPs), can be used to demonstrate quantitative genetic variation in natural populations. Variation at two levels is considered: among pairs of individuals within populations, and among pairs of subpopulations within a population. In the former, inferred pairwise relatedness, combined with trait measures, allow estimates of heritability 'in the wild'. In the latter, estimates of QST are obtained, in the absence of known heritabilities, via estimates of pairwise FST. Estimators of relatedness based on the 'Kronecker operator' are given. Both methods require actual variation of relationship, a rarely studied aspect of population structure, and not necessarily present. Some conditions for appropriate population structures in the wild are identified, in part through a review of recent studies.

Animals↗

PubMed2001

Angiotensinogen in essential hypertension: from genetics to nephrology.

There is general consensus that genetic variation accounts in part for individual susceptibilities to essential hypertension. In marked contrast to classic mendelian disorders, in which genetic alterations produce a gain or loss of function, genetic determinants of essential hypertension, high blood pressure of unknown cause, are expected to be small, achieving significance through the cumulative effects of environmental exposure over the course of a lifetime. Whether and how genetic factors that contribute to common diseases can be identified remain unclear. Research on a link between angiotensinogen and essential hypertension illustrates a path that began in genetics and is now leading toward nephrology. Various challenges encountered along the way may prove to be characteristic features of genetic investigations of the pathogenesis of common diseases. The implication of a gene by statistical analysis is only the beginning of a protracted process of functional analysis at increasing levels of biologic integration. The ultimate goal is to develop an understanding of the manner in which genetic variation at a locus can affect a physiologic parameter and to extract from this inference new knowledge of significance for the prevention or treatment of disease.

Alleles↗