Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “quantitative genetics”

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.

At least 1,153 records · Page 64Linked to original sources
PubMed2003

Quantitative trait loci for femoral size and shape in a genetically heterogeneous mouse population.

UNLABELLED: The aim of this study was to examine the genetic effects on cortical bone geometry. Genotypes from 487 mice were compared with geometric traits obtained from microCT. We found 14 genetic markers that associate with geometric traits, showing the complexity of genetic control over bone geometry. INTRODUCTION: Previous studies have shown that genetic background affects bone characteristics, particularly bone mineral density, in both mouse and human populations. Much less is known, however, about the effects of polymorphic genes on bone size, shape, and mechanical integrity. In this study, we investigated the genetic determinants of geometric properties of cortical bone in mice. MATERIALS AND METHODS: This study used a genetically heterogeneous mouse population, which is denoted UM-HET3 stock and is derived as the progeny of (BALB/cJ X C57BL/6J) F1 females and (C3H/HeJ X DBA/2J) F1 males. The experimental group consisted of 487 female UM-HET3 mice. Genotypic data from 99 polymorphic genetic loci was obtained from the mice at 4 weeks of age. At 18 months of age, the mice were humanely killed, and the right femurs were scanned with microcomputed tomography to assess geometric properties of cortical bone. A permutation-based test was used to detect significant associations between genetic markers and geometric traits. This test generates experiment-wise p values, which account for the effect of testing multiple hypotheses. An experiment-wise p < or = 0.05 was considered statistically significant. RESULTS: Fourteen genetic markers were found to significantly associate with one or more geometric traits. Two markers (D3Mit62 and D4Mit155) were associated with traits describing bone size; 2 (D12Mit167 and D14Mit170) were linked with traits describing bone shape; and 10 (D1Nds2, D5Mit95, D6Mit216, D7Mit91, D8Mit51, D9Mit110, D11Mit83, D15Mit100, D15Mit171, and D17Mit46) were associated with both size and shape. CONCLUSIONS: Our results indicate that the genetic control of cortical bone geometry is complex and that femoral size and shape may be influenced by different, although overlapping, groups of polymorphic loci.

Animals↗
PubMed2005

Genetic architecture of qualitative and quantitative Melampsora larici-populina leaf rust resistance in hybrid poplar: genetic mapping and QTL detection.

In order to elucidate the genetic control of resistance to Melampsora larici-populina leaf rust in hybrid poplars, a Populus deltoides x P. trichocarpa F(1) progeny was analysed for qualitative and quantitative rust resistances. This progeny was evaluated for three components of quantitative resistance (latent period, uredinia number and uredinia size) to seven M. larici-populina strains in controlled conditions, and for one component of field susceptibility (rust colonization on the most infected leaf). One qualitative resistance locus inherited from P. deltoides, R(1), was localized on the genetic map. It segregates 1 : 1 in the F(1) progeny and is effective against four of the studied strains. QTL analysis was performed separately on R(1) and r(1) genotype subsets. An additional detection was conducted on the entire F(1) progeny for the three strains able to overcome R(1) and for MAX2. A total of nine QTLs were detected. Two had large, broad-spectrum effects. One (R(US)) is inherited from the P. trichocarpa parent; the other is inherited from P. deltoides and colocalized with R(1). Seven QTLs had only limited and specific effects. Significant interaction effects were detected mainly between the two major QTLs. Implications of these results for durable resistance breeding strategies, and possible benefits from the Populus genome sequence, are discussed.

Basidiomycota↗
PubMed2001

Assessment of the ratio of pollen to seed flow in a cline for genetic variation in a quantitative trait.

A dispersal-selection cline model is analysed to evaluate the role of the ratio of pollen to seed flow (r) in spatial genetic variation, with a focus on clines in additive and dominant variances of major genes affecting a quantitative trait, assuming one locus with two alleles, no genetic drift and no mutation. It is shown that under weak selection, steady-state departures from the value at Hardy-Weinberg equilibrium (HWE) for genotype frequency (D) and additive variance (DeltaVa) generally display a small value on one side of the selection boundary point, a high value around the point, and a moderate value on the other side of the boundary point. A large value of r can enhance formation of this pattern. However, this is not the case for clines in the average effect of a gene substitution (Deltaalpha) or in dominance variance (DeltaVd), where large values of r can eradicate the clines. Direct use of their values at HWE to approximate the real case is acceptable. There is an expected turning point that divides clines of either additive variance or dominance variance into two subclines, each with a shorter width than that of allele frequency. Integration of these properties can help to indicate the existence of major genes affecting a quantitative trait.

Gene Frequency↗
PubMed2004

Conserved genetic basis of a quantitative plumage trait involved in mate choice.

A key question in evolutionary genetics is whether shared genetic mechanisms underlie the independent evolution of similar phenotypes across phylogenetically divergent lineages. Here we show that in two classic examples of melanic plumage polymorphisms in birds, lesser snow geese (Anser c. caerulescens) and arctic skuas (Stercorarius parasiticus), melanism is perfectly associated with variation in the melanocortin-1 receptor (MC1R) gene. In both species, the degree of melanism correlates with the number of copies of variant MC1R alleles. Phylogenetic reconstructions of variant MC1R alleles in geese and skuas show that melanism is a derived trait that evolved in the Pleistocene.

Animals↗
PubMed1988

A genetic assay for aneuploidy: quantitation of chromosome loss using a mouse/human monochromosomal hybrid cell line.

A genetic assay is described in which a mouse/human hybrid cell line R3-5 containing a single human chromosome (a monochromosomal hybrid) is used to detect chemically induced aneuploidy. In this assay the frequency of chromosome loss determined by the cloning efficiency of the cells in a selection medium is used as an index for the potential of a chemical to induce aneuploidy. The hybrid cells are deficient in hypoxanthine guanine phosphoribosyltransferase (HGPRT) and contain human chromosome 2, marked with Ecogpt, an E. coli gene for xanthine guanine phosphoribosyltransferase. These cells with a genotype of hgprt-/Ecogpt+ can grow in medium containing mycophenolic acid and xanthine (MX medium) but not in medium containing 6-thioguanine (6-TG). The loss of the human chromosome from R3-5 cells as a result of chemical treatment produces cells with a genotype of hgprt-/Ecogpt- which are capable of growth in the medium containing 6-TG. Thus, the cloning efficiency of cells treated with a test chemical in 6-TG provides a method to determine the frequency of cells that have lost the human chromosome. Two chemicals, colcemid and nocodazole, previously known to induce aneuploidy in mammalian cells were used for a preliminary evaluation of this test system. Both of these compounds at concentrations ranging from 0.002 to 0.032 micrograms/ml showed a concentration-related positive response in this assay.

Aneuploidy↗
PubMedDate not supplied

A sibling-pair based approach for mapping genetic loci that influence quantitative measures of reading disability.

Family and twin studies consistently demonstrate a significant role for genetic factors in the aetiology of the reading disorder dyslexia. However, dyslexia is complex at both the genetic and phenotypic levels, and currently the nature of the core deficit or deficits remains uncertain. Traditional approaches for mapping disease genes, originally developed for single-gene disorders, have limited success when there is not a simple relationship between genotype and phenotype. Recent advances in high-throughput genotyping technology and quantitative statistical methods have made a new approach to identifying genes involved in complex disorders possible. The method involves assessing the genetic similarity of many sibling pairs along the lengths of all their chromosomes and attempting to correlate this similarity with that of their phenotypic scores. We are adopting this approach in an ongoing genome-wide search for genes involved in dyslexia susceptibility, and have already successfully applied the method by replicating results from previous studies suggesting that a quantitative trait locus at 6p21.3 influences reading disability.

Chromosome Mapping↗
PubMed1997

Assessment of learning by the Morris water task and fear conditioning in inbred mouse strains and F1 hybrids: implications of genetic background for single gene mutations and quantitative trait loci analyses.

Genetic methods including the creation of transgenic or null mutant models and mapping studies using quantitative trait loci strategies can be used to identify candidate genes in mice that regulate learning processes. Interpretations as to the impact of single gene mutations for polygenic behaviours like learning will depend in part on the genetic background of the animals used for these manipulations. To address the issue of genetic variability, 12 inbred strains and seven different F1 hybrids were tested on multiple behavioural tasks, including two complex learning paradigms: the Morris water task and fear conditioning. Strain differences were found for all variables measured. In the hidden platform version of the Morris task, the albino animals performed poorly while overall the F1 hybrids showed the best selectivity for the trained quadrant as measured in a probe trial. In contrast, almost all genotypes performed well on the contextual fear conditioning task and learned to associate the test context with the pairing of a foot shock and auditory stimulus as demonstrated 24 h after training by increased freezing in the test environment compared to an altered context. Significant genetic correlations were obtained for behavioural measures suggesting that the same genes regulate various aspects of performance on behavioural tasks. Scores from these multiple inbred strains and F1 hybrids provide a baseline level of learning ability for fear conditioning and the Morris water task. The results of the present study confirm the importance of genetic background in the performance of various learning tasks. This variability should be considered when developing new transgenic or null mutant animal models.

Acoustic Stimulation↗
PubMed2001

Understanding the roles of genome and envirome: methods in genetic epidemiology.

BACKGROUND: In order to understand studies of psychiatric epidemiology focusing on the 'genome' and 'envirome', basic knowledge of the logic and methods is necessary. AIMS: To provide a review of typical methods used in genetic epidemiology. METHOD: Reviews of the research designs usually employed in quantitative and molecular genetic studies. Genotype-environment correlation and interaction are also discussed. RESULTS: Quantitative genetic studies indicate that genetic influences are important for both psychiatric disorders and behavioural traits. Specific gene loci can be tested for associations with both psychiatric risk and behavioural traits by means of molecular genetic techniques. There has been little examination of genotype-environment correlation and interaction, although the few reports that have appeared suggest that these complex relationships are important. CONCLUSIONS: Advances in quantitative and molecular genetics now permit more careful examination of genotype-environment interaction and correlation. Studies combining molecular genetic strategies with measurement of the environment are still at an early stage, however, and their results must be awaited.

Environment↗
PubMed1996

Genetic neural networks for quantitative structure-activity relationships: improvements and application of benzodiazepine affinity for benzodiazepine/GABAA receptors.

A novel tool, called a genetic neural network (GNN), has been developed for obtaining quantitative structure-activity relationships (QSAR) for high-dimensional data sets (J. Med. Chem. 1996, 39, 1521-1530). The GNN method uses a neural network to correlate activity with descriptors that are preselected by a genetic algorithm. To provide an extended test of the GNN method, the data on 57 benzodiazepines given by Maddalena and Johnston (MJ; J. Med. Chem. 1995, 38, 715-724) have been examined with an enhanced version of GNN, and the results are compared with the excellent QSAR of MJ. The problematic steepest descent training has been replaced by the scaled conjugate gradient algorithm. This leads to a substantial gain in performance in both robustness of prediction and speed of computation. The cross-validation GNN simulation and the subsequent run based on an unbiased and more efficient protocol led to the discovery of other 10-descriptor QSARs that are superior to the best model of MJ based on backward elimination selection and neural network training. Results from a series of GNNs with a different number of inputs showed that a neural network with fewer inputs can produce QSARs as good as or even better than those with higher dimensions. The top-ranking models from a GNN simulation using only six input descriptors are presented, and the chemical significance of the chosen descriptors is discussed. The statistical significance of these GNN QSARs is validated. The best QSARs are used to provide a graphical tool that aids the design of new drug analogues. By replacing functional groups at the 7- and 2'-positions with ones that have optimal substituent parameters, a number of new benzodiazepines with high potency are predicted.

Algorithms↗
PubMed1998

Levels of genetic polymorphism: marker loci versus quantitative traits.

Species are the units used to measure ecological diversity and alleles are the units of genetic diversity. Genetic variation within and among species has been documented most extensively using allozyme electrophoresis. This reveals wide differences in genetic variability within, and genetic distances among, species, demonstrating that species are not equivalent units of diversity. The extent to which the pattern observed for allozymes can be used to infer patterns of genetic variation in quantitative traits depends on the forces generating and maintaining variability. Allozyme variation is probably not strictly neutral but, nevertheless, heterozygosity is expected to be influenced by population size and genetic distance will be affected by time since divergence. The same is true for quantitative traits influenced by many genes and under weak stabilizing selection. However, the limited data available suggest that allozyme variability is a poor predictor of genetic variation in quantitative traits within populations. It is a better predictor of general phenotypic divergence and of postzygotic isolation between populations or species, but is only weakly correlated with prezygotic isolation. Studies of grasshopper and planthopper mating signal variation and assortative mating illustrate how these characters evolve independently of general genetic and morphological variation. The role of such traits in prezygotic isolation, and hence speciation, means that they will contribute significantly to the diversity of levels of genetic variation within and among species.

Alleles↗
PubMed1991

Isolation by distance in a quantitative trait.

Random genetic drift in a quantitative character is modeled for a population with a continuous spatial distribution in an infinite habitat of one or two dimensions. The analysis extends Wright's concept of neighborhood size to spatially autocorrelated sampling variation in the expected phenotype at different locations. Weak stabilizing selection is assumed to operate toward the same optimum phenotype in every locality, and the distribution of dispersal distances from parent to offspring is a (radially) symmetric function. The equilibrium pattern of geographic variation in the expected local phenotype depends on the neighborhood size, the genetic variance within neighborhoods, and the strength of selection, but is nearly independent of the form of the dispersal function. With all else equal, geographic variance is smaller in a two-dimensional habitat than in one dimension, and the covariance between expected local phenotypes decreases more rapidly with the distance separating them in two dimensions than in one. The equilibrium geographic variance is less than the phenotypic variance within localities, unless the neighborhood size is small and selection is extremely weak, especially in two dimensions. Nevertheless, dispersal of geographic variance created by random genetic drift is an important mechanism maintaining genetic variance within local populations. For a Gaussian dispersal function it is shown that, even with a small neighborhood size, a population in a two-dimensional habitat can maintain within neighborhoods most of the genetic variance that would occur in an infinite panmictic population.

Gene Frequency↗
PubMed1997

Genetic analysis of a quantitative trait in a mouse model of polycystic kidney disease.

The development of a variety of powerful tools for genome analysis has facilitated the ability to genetically map loci which contribute to the variation of a quantitative trait. However, the fact that these traits are often determined as a result of complex genetic interactions has made their analysis considerably more difficult then the molecular characterization of qualitative traits that are monogenic in origin. We have described the use of a novel method of chromosomal exclusion to map the recessive mutation juvenile cystic kidney (jck) to mouse chromosome 11 using an intercross between (C57BL/6J x DBA/2J) F1 jck/+ mice. The severity of polycystic kidney disease (PKD) in the intercross progeny, which could be quantitated as a function of kidney size, was significantly more variable than that found in the parental C57BL/6J strain, suggesting that a modifier locus or loci introduced from DBA/2J affects expression of jck. Two regions (one from DBA/2J on chromosome 10 and a second from C57BL/6J on chromosome 1) were found to be associated with inheritance of a more severe PKD phenotype. The finding of a highly significant association of inheritance of a C57BL/6J-related locus with disease severity was unexpected since the PKD phenotype in this inbred background is mild. This result suggests that inheritance in the affected F2 mice of loci from the two different parental backgrounds results in the more severe phenotype, presumably as a consequence of a direct or indirect interaction between their protein products. This type of effect, which is an example of genetic epistasis, will make the molecular characterization of loci that contribute to complex traits markedly more difficult than the analysis of monogenic disorders.

Animals↗
PubMed1999

Real-time quantitative PCR detection of genetically modified Maximizer maize and Roundup Ready soybean in some representative foods.

A fast and quantitative method was developed to detect transgenic "Maximizer" maize "event 176" (Novartis) and "Roundup Ready" soybean (Monsanto) in food by real-time quantitative PCR. The use of the ABI Prism 7700 sequence detection system allowed the determination of the amplified product accumulation through a fluorogenic probe (TaqMan). Fluorescent dyes were chosen in such a way as to coamplify total and transgenic DNA in the same tube. Using real-time quantitative PCR, 2 pg of transgenic or total DNA per gram of starting sample was detected in 3 h after DNA extraction and the relative amounts of "Maximizer" maize and "Roundup Ready" soybean in some representative food products were quantified.

DNA↗
PubMed2002

The genetic variance for multiple linked quantitative trait loci conditional on marker information in a crossed population.

In the prediction of genetic values and quantitative trait loci (QTLs) mapping via the mixed model method incorporating marker information in animal populations, it is important to model the genetic variance for individuals with an arbitrary pedigree structure. In this study, for a crossed population originated from different genetic groups such as breeds or outbred strains, the variance of additive genetic values for multiple linked QTLs that are contained in a chromosome segment, especially the segregation variance, is investigated assuming the use of marker data. The variance for a finite number of QTLs in one chromosomal segment is first examined for the crossed population with the general pedigree. Then, applying the concept of the expectation of identity-by-descent proportion, an approximation to the mean of the conditional probabilities for the linked QTLs over all loci is obtained, and using it an expression for the variance in the case of an infinite number of linked QTLs marked by flanking markers is derived. It appears that the approach presented can be useful in the segment mapping using, and in the genetic evaluation of, crosses with general pedigrees in the population of concern. The calculation of the segregation variance through the current approach is illustrated numerically, using a small data-set.

Genetic Linkage↗
PubMed2006

Models and partition of variance for quantitative trait loci with epistasis and linkage disequilibrium.

BACKGROUND: A genetic model about quantitative trait loci (QTL) provides a basis to interpret the genetic basis of quantitative traits in a study population, such as additive, dominance and epistatic effects of QTL and the partition of genetic variance. The standard quantitative genetics model is based on the least squares partition of genetic effects and also genetic variance in an equilibrium population. However, over years many specialized QTL models have also been proposed for applications in some specific populations. How are these models related? How to analyze and partition a QTL model and genetic variance when both epistasis and linkage disequilibrium are considered? RESULTS: Starting from the classical description of Cockerham genetic model, we first represent the model in a multiple regression setting by using indicator variables to describe the segregation of QTL alleles. In this setting, the definition of additive, dominance and epistatic effects of QTL and the basis for the partition of genetic variance are elaborated. We then build the connection between this general genetic model and a few specialized models (a haploid model, a diploid F2 model and a general two-allele model), and derive the genetic effects and partition of genetic variance for multiple QTL with epistasis and linkage disequilibrium for these specialized models. CONCLUSION: In this paper, we study extensively the composition and property of the genetic model parameters, such as genetic effects and partition of genetic variance, when both epistasis and linkage disequilibrium are considered. This is the first time that both epistasis and linkage disequilibrium are considered in modeling multiple QTL. This analysis would help us to understand the structure of genetic parameters and relationship of various genetic quantities, such as allelic frequencies and linkage disequilibrium, on the definition of genetic effects, and will also help us to understand and properly interpret estimates of the genetic effects and variance components in a QTL mapping experiment.

Algorithms↗
PubMed1992

On the use of the moments method of estimation to obtain approximate maximum likelihood estimates of linkage between a genetic marker and a quantitative locus.

The approximate maximum likelihood method of Luo & Kearsey (1989) to determine the parameters of a segregating quantitative trait locus (QTL) in an F2 population by linkage to a genetic marker is compared to the 'true' maximum likelihood estimates derived by scanning the seven parameter likelihood space. The two methods did not yield identical results, and diverged markedly for a dominant QTL loosely linked to the genetic marker. Further study is suggested to evaluate other methods that do not simultaneously maximize the likelihood for all parameters.

Genetic Linkage↗
PubMed1996

Quantitative trait loci in genetically hypertensive rats. Possible sex specificity.

We performed a total genome screen in an F2 cross derived from the stroke-prone spontaneously hypertensive rat and the normotensive Wistar-Kyoto rat. Blood pressure at baseline and after 1% NaCl was measured by radiotelemetry; other phenotypes included heart rate, motor activity, left ventricle weight to body weight ratio, and vascular smooth muscle cell polyploidy, a measure of vascular hypertrophy. Quantitative trait loci affecting a given phenotype were mapped relative to microsatellite markers by using the MAPMAKER/QTL 1.1 computer package. We identified three blood pressure quantitative trait loci, two on rat chromosome 2 and one on rat chromosome 3. The quantitative trait loci close to genetic markers D2Mgh12 ("suggestive" linkage, with a maximal logarithm of the odds [LOD] score of 3.1) and D3Mgh16 (significant linkage, with a maximal LOD score of 5.6) showed possible sex specificity in the male F2 cohort only. This was confirmed by the likelihood ratio test for the difference in locus effects between the sexes. We also identified a new quantitative trait locus for LV hypertrophy on rat chromosome 14 ("suggestive" linkage, with a maximal LOD score of 3.1). The sex specificity of blood pressure quantitative trait loci will be important in designing congenic strains and substrains for fine genetic mapping and for identifying genes that regulate blood pressure.

Animals↗