Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “programmed genetic 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.

At least 847 records · Page 47Linked to original sources

Should genetic groups be fitted in BLUP evaluation? Practical answer for the French AI beef sire evaluation.

Some analytical and simulated criteria were used to determine whether a priori genetic differences among groups, which are not accounted for by the relationship matrix, ought to be fitted in models for genetic evaluation, depending on the data structure and the accuracy of the evaluation. These criteria were the mean square error of some extreme contrasts between animals, the true genetic superiority of animals selected across groups, i.e. the selection response, and the magnitude of selection bias (difference between true and predicted selection responses). The different statistical models studied considered either fixed or random genetic groups (based on six different years of birth) versus ignoring the genetic group effects in a sire model. Including fixed genetic groups led to an overestimation of selection response under BLUP selection across groups despite the unbiasedness of the estimation, i.e. despite the correct estimation of differences between genetic groups. This overestimation was extremely important in numerical applications which considered two kinds of within-station progeny test designs for French purebred beef cattle AI sire evaluation across years: the reference sire design and the repeater sire design. When assuming a priori genetic differences due to the existence of a genetic trend of around 20% of genetic standard deviation for a trait with h2=0.4, in a repeater sire design, the overestimation of the genetic superiority of bulls selected across groups varied from about 10% for an across-year selection rate p=1/6 and an accurate selection index (100 progeny records per sire) to 75% for p=1/2 and a less accurate selection index (20 progeny records per sire). This overestimation decreased when the genetic trend, the heritability of the trait, the accuracy of the evaluation or the connectedness of the design increased. Whatever the data design, a model of genetic evaluation without groups was preferred to a model with genetic groups when the genetic trend was in the range of likely values in cattle breeding programs (0 to 20% of genetic standard deviation). In such a case, including random groups was pointless and including fixed groups led to a large overestimation of selection response, smaller true selection response across groups and larger variance of estimation of the differences between groups. Although the genetic trend was correctly predicted by a model fitting fixed genetic groups, important errors in predicting individual breeding values led to incorrect ranking of animals across groups and, consequently, led to lower selection response.

Animals↗

Development of ESTs from chickpea roots and their use in diversity analysis of the Cicer genus.

BACKGROUND: Chickpea is a major crop in many drier regions of the world where it is an important protein-rich food and an increasingly valuable traded commodity. The wild annual Cicer species are known to possess unique sources of resistance to pests and diseases, and tolerance to environmental stresses. However, there has been limited utilization of these wild species by chickpea breeding programs due to interspecific crossing barriers and deleterious linkage drag. Molecular genetic diversity analysis may help predict which accessions are most likely to produce fertile progeny when crossed with chickpea cultivars. While, trait-markers may provide an effective tool for breaking linkage drag. Although SSR markers are the assay of choice for marker-assisted selection of specific traits in conventional breeding populations, they may not provide reliable estimates of interspecific diversity, and may lose selective power in backcross programs based on interspecific introgressions. Thus, we have pursued the development of gene-based markers to resolve these problems and to provide candidate gene markers for QTL mapping of important agronomic traits. RESULTS: An EST library was constructed after subtractive suppressive hybridization (SSH) of root tissue from two very closely related chickpea genotypes (Cicer arietinum). A total of 106 EST-based markers were designed from 477 sequences with functional annotations and these were tested on C. arietinum. Forty-four EST markers were polymorphic when screened across nine Cicer species (including the cultigen). Parsimony and PCoA analysis of the resultant EST-marker dataset indicated that most accessions cluster in accordance with the previously defined classification of primary (C. arietinum, C. echinospermum and C. reticulatum), secondary (C. pinnatifidum, C. bijugum and C. judaicum), and tertiary (C. yamashitae, C. chrossanicum and C. cuneatum) gene-pools. A large proportion of EST alleles (45%) were only present in one or two of the accessions tested whilst the others were represented in up to twelve of the accessions tested. CONCLUSION: Gene-based markers have proven to be effective tools for diversity analysis in Cicer and EST diversity analysis may be useful in identifying promising candidates for interspecific hybridization programs. The EST markers generated in this study have detected high levels of polymorphism amongst both common and rare alleles. This suggests that they would be useful for allele-mining of germplasm collections for identification of candidate accessions in the search for new sources of resistance to pests / diseases, and tolerance to abiotic stresses.

Biomarkers↗

Fingerprinting method for phylogenetic classification and identification of microorganisms based on variation in 16S rRNA gene sequences.

The paper describes a method for the classification and identification of microorganisms based on variations in 16S rRNA sequences. The 16S rRNA is one of the most conserved molecules within a cell. The nature of the variable and spacer regions has been found to be specific to a given organism. Thus, the method presented here can be very useful for the classification and identification of microorganisms for which very little information is available. To automate the method, a comprehensive computer program called FPMAP has been developed for the analysis of restriction fragment pattern data. The method involves the restriction digestion of genomic DNA, preferably using four-cutters that may recognize 6-9 sites within the 16S rDNA. The fragments are separated on a polyacrylamide gel along with a suitable marker, then transferred into a nylon membrane and hybridized with a radiolabeled 16S rDNA probe. After autoradiography, the fragment sizes are calculated, and the data are analyzed using the FPMAP software. We demonstrate that the method can be used for identification of strains of Streptomyces and mycobacteria. The software is available from our ftp site ftp:¿imtech.chd.nic.in/pub/com/fpmap/unix/.

Autoanalysis↗

[Determination of the indices of genetic similarity and diversity using programmable microcomputers].

A complex of programs for microcomputer permitting to compute the similarity and diversity indices of two or few populations, herds, intrabreed types, lines and related groups of animals in automatic operation has been suggested. The absolute values of occurrence of factors and the gene frequencies in polymorphic systems of serum proteins and erythrocyte antigens of blood groups are used in calculation.

Animals↗

Genetic variation and risk of sepsis.

Sepsis is the leading cause of death in non-coronary intensive care unit patients. Sepsis is caused by the immune response to infection and is manifest by pain, fever and edema as the result of the activation of coagulation and inflammatory responses. In severe cases, sepsis leads to organ dysfunction and failure. Sepsis affects more than 750,000 people each year in the US alone, with a mortality rate of over 35 percent making it one of the leading causes of death in developed countries. In addition many patients that die of other diseases have their hospital courses complicated by sepsis. Most patients with infection do not develop severe sepsis and septic shock and yet those that do have a significantly increased risk of death. Genetic and environmental variables may influence why one patient with infection gets sicker than the next. For example, people may be programmed to respond to infection in different ways; some with aggressive immune responses that may be able to wipe out infection before it manifests itself in physical symptoms, while others may have less aggressive immune systems that allow them to get sick more often. The discovery of various common genetic polymorphisms in genes that control the inflammatory response (e.g. tumor necrosis factor) has lent credence to this hypothesis. Yet discovery of the actual relationship between risks of infection / severe sepsis and individual genotypes will require larger, more rigorously designed studies.

Animals↗

The GP problem: quantifying gene-to-phenotype relationships.

In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

Computer Simulation↗

Prospects for admixture mapping of complex traits.

Admixture mapping extends to human populations the principles that underlie linkage analysis of an experimental cross. For detecting genes that contribute to ethnic variation in disease risk, admixture mapping has greater statistical power than family-linkage studies. In comparison with association studies, admixture mapping requires far fewer markers to search the genome and is less affected by allelic heterogeneity. Statistical-analysis programs for admixture mapping are now available, and a genomewide panel of markers for admixture mapping in populations formed by West African-European admixture has been assembled. Some of the remaining technical challenges include the ability to ensure that the statistical methods are robust and to develop marker panels for other admixed populations. Where admixed populations and panels of markers informative for ancestry are available, admixture mapping can be applied to localize genes that contribute to ethnic variation in any measurable trait.

Black People↗

Plant genomics: the third wave.

Completing the primary genomic sequence of Arabidopsis thaliana was a major milestone, being the first plant genome and only the third high-quality finished eukaryotic genome sequence. Understanding how the genome sequence comprehensively encodes developmental programs and environmental responses is the next major challenge for all plant genome projects. This requires fully characterizing the genes, the regulatory sequences, and their functions. We discuss several functional genomics approaches to decode the linear sequence of the reference plant Arabidopsis thaliana, including full-length cDNA collections, microarrays, natural variation, knockout collections, and comparative sequence analysis. Genomics provides the essential tools to speed the work of the traditional molecular geneticist and is now a scientific discipline in its own right.

Arabidopsis↗

De novo design of the hydrophobic core of ubiquitin.

We have previously reported the development and evaluation of a computational program to assist in the design of hydrophobic cores of proteins. In an effort to investigate the role of core packing in protein structure, we have used this program, referred to as Repacking of Cores (ROC), to design several variants of the protein ubiquitin. Nine ubiquitin variants containing from three to eight hydrophobic core mutations were constructed, purified, and characterized in terms of their stability and their ability to adopt a uniquely folded native-like conformation. In general, designed ubiquitin variants are more stable than control variants in which the hydrophobic core was chosen randomly. However, in contrast to previous results with 434 cro, all designs are destabilized relative to the wild-type (WT) protein. This raises the possibility that beta-sheet structures have more stringent packing requirements than alpha-helical proteins. A more striking observation is that all variants, including random controls, adopt fairly well-defined conformations, regardless of their stability. This result supports conclusions from the cro studies that non-core residues contribute significantly to the conformational uniqueness of these proteins while core packing largely affects protein stability and has less impact on the nature or uniqueness of the fold. Concurrent with the above work, we used stability data on the nine ubiquitin variants to evaluate and improve the predictive ability of our core packing algorithm. Additional versions of the program were generated that differ in potential function parameters and sampling of side chain conformers. Reasonable correlations between experimental and predicted stabilities suggest the program will be useful in future studies to design variants with stabilities closer to that of the native protein. Taken together, the present study provides further clarification of the role of specific packing interactions in protein structure and stability, and demonstrates the benefit of using systematic computational methods to predict core packing arrangements for the design of proteins.

Algorithms↗

Heterogeneity of glucose-6-phosphate dehydrogenase enzymopathies in the GDR.

G6PD variants of 13 patients from 12 German families with different clinical symptoms have been characterized kinetically. Vmax G6PD was nearly zero in red blood cells of all carriers. Therefore G6PD variants were isolated from leucocytes, which proved to be a suitable source for analysis of instable G6PD variants. The testing program included KmG6P, KmNADP, Ki values of NADPH, ATP and 2,3 P2G, rate of utilization of dG6P, Gal6P, dNADP, NAD, and pH dependence. From the results obtained one can conclude that all analyzed G6PD variants represent individual mutations. The degree of metabolic dysregulation can be explained by the different kinetic and physico-chemical properties of these G6PD variants.

Erythrocytes↗

Analysis and interpretation of short tandem repeat microvariants and three-banded allele patterns using multiple allele detection systems.

The Palm Beach County Sheriffs Office (PBSO) Crime Laboratory and the Alabama Department of Forensic Sciences (ADFS) have validated and implemented analysis of short tandem repeat (STR) sequences on casework using silver staining kit and SYBR Green I detection systems and are presently validating fluorescently tagged STR alleles using the Hitachi FMBIO 100 instrument. Concurrently, the Broward County Sheriff's Office (BSO) Crime Laboratory is validating the ABI Prism310 Genetic Analyzer capillary electrophoresis STR detection system (ABI CE310) from Perkin Elmer Applied BioSystems. During the course of analyzing over 10,000 individuals for the STR loci CSF1PO, TPOX and THO1 (CTT) using silver staining for allele detection, 42 samples demonstrated alleles that were "off ladder," contained three-banded patterns at a single locus, or exhibited an apparent THO1 "9.3,10" allele pattern. PBSO, ADFS and BSO Crime Laboratories have collaborated on the verification of the allele patterns observed in these 42 samples using the following allele detection systems: (1) manual silver staining, (2) SYBR Green I staining, and/or (3) fluorescently tagged amplified products separated by polyacrylamide gel electrophoresis or capillary electrophoresis followed by laser detection. Regardless of the CTT allele detection system utilized, concordant results were obtained for 41 of the 42 samples. The only exception was a sample in which a wide band within the THO1 locus was identified as a THO1 "9.3, 10" genotype by silver staining kit and SYBR Green I staining but was verified to be a THO1 "9.3" homozygote by all other allele detection systems. Manual allele detection could readily identify microvariants, as a visual assessment of stained gels clearly shows that alleles do not migrate coincident with well-characterized allele size standards. As would be predicted, however, the manual detection systems did not provide adequate resolution to approximate the basepair size for off-ladder variants. All fluorescent software program systems were consistent in designating alleles "not in range" or "off ladder," thereby indicating true microvariants. All single-locus three-banded patterns were detected using all of the STR multiplex systems. In addition, individual locus-specific primers verified multiplexed amplified products were specific for the locus in question.

Alleles↗

Crypthecodinium and Tetrahymena: an exercise in comparative evolution.

Nucleotide sequences have been determined for the highly variable D2 region of the large rRNA molecule for over 60 strains of dinoflagellates. These strains were selected from a worldwide collection that represents all the known sibling species (compatibility groups, Mendelian species) in the sibling swarm referred to as Crypthecodinium cohnii. A phylogenetic tree has been constructed from an analysis of the variations in a length of about 180 bases, using PHYLOGEN string analysis programs. The Crypthecodinium tree is compared with the previously published but here augmented tree constructed upon the same rRNA region for the sibling species of a worldwide collection of ciliated protozoa related to the genus Tetrahymena. The first reported sequence of Lambornella clarki, the parasite of tree-hole mosquitoes, is included. The dinoflagellate species complex is much more homogeneous with respect to ribosomal variation. The mean number of differences among sequences from different Crypthecodinium species is about 7, in comparison with 22 differences among the ciliate species examined. Moreover, all the diversity in the dinoflagellates can be explained by base substitutions, whereas insertions and deletions are common in the ciliates. The dinoflagellates are also much more uniform with respect to nutritional and genetic economies. The two complexes differ also in the relationship between molecular variations and breeding compatibility. All tetrahymenine sibling species thus far examined are monomorphic in the D2 region, but several dinoflagellate species are polymorphic. Several different dinoflagellate species, moreover, have identical D2 regions. This kind of ribosomal identity of incompatible strains is found in these ciliates only in one tight cluster of species--Group C. The tetrahymenine swarm is apparently much older than the Crypthecodinium swarm, and the dinoflagellate species produce incompatible progeny species much more readily than do the ciliates, perhaps by the acquisition of mutations that potentiate incompatibility in sympatric populations.

Animals↗

SequenceLDhot: detecting recombination hotspots.

MOTIVATION: There is much local variation in recombination rates across the human genome--with the majority of recombination occurring in recombination hotspots--short regions of around approximately 2 kb in length that have much higher recombination rates than neighbouring regions. Knowledge of this local variation is important, e.g. in the design and analysis of association studies for disease genes. Population genetic data, such as that generated by the HapMap project, can be used to infer the location of these hotspots. We present a new, efficient and powerful method for detecting recombination hotspots from population data. RESULTS: We compare our method with four current methods for detecting hotspots. It is orders of magnitude quicker, and has greater power, than two related approaches. It appears to be more powerful than HotspotFisher, though less accurate at inferring the precise positions of the hotspot. It was also more powerful than LDhot in some situations: particularly for weaker hotspots (10-40 times the background rate) when SNP density is lower (< 1/kb). AVAILABILITY: Program, data sets, and full details of results are available at: http://www.maths.lancs.ac.uk/~fearnhea/Hotspot.

Algorithms↗

Genetic influences on blood pressure with the cold-pressor test: a twin study.

OBJECTIVES: To determine the genetic and environmental contributions to resting blood pressure, the level of blood pressure during the cold-pressor test and the increase in blood pressure with the cold-pressor test in an adult cohort of normotensive twins. DESIGN AND METHODS: Ninety-one monozygotic and 41 dizygotic normal twin pairs were recruited by advertisement. The mean age was 34 +/- 14 years (mean +/- SD). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were measured continuously at the finger (using a Finapres device) and verified at the upper arm oscillometrically (using a Dinamap device) every minute. The cold-pressor test was conducted by immersing the non-dominant hand into cold (< 4 degrees C) water for 2 min. Statistical analysis was performed by using the SPSS program; parameters of the quantitative genetic models were estimated by path-analysis techniques using the LISREL 8 program. RESULTS: Heritability estimates of additive genetic effects were statistically significant for SBP and DBP but not for heart rate during rest and during the cold-pressor test. Furthermore, the path analysis indicated shared as well as specific genetic components both for the blood pressure level at rest and for that during the cold-pressor test. However, the genetic influences on the blood pressure level at rest and on the increase in blood pressure during the cold-pressor test (the blood pressure level during the cold-pressor test minus that during rest) were entirely independent of one another. CONCLUSIONS: A significant genetic covariation exists for SBP and DBP during rest and during the cold-pressor test, as well as a significant genetic variation that is specific to the cold-pressor stress condition. These findings suggest that different genes or sets of genes contribute to blood pressure regulation during rest and to blood pressure reactivity to cold-pressor stress.

Adult↗

A twin study for serum leptin, soluble leptin receptor, and free insulin-like growth factor-I in pubertal females.

CONTEXT: Leptin and IGF-I are two peripheral metabolic signals linking body energy status to hypothalamus GnRH generator and involved in the pubertal development and metabolic disorders. The changes of their biological activity through puberty and the genetic basis are not clear. OBJECTIVE: To determine the genetic and environmental influences to the variations of basal leptin, soluble leptin receptor (SOB-R), free leptin index (FLI), and free IGF-I levels in pubertal females. DESIGN: A twin study was performed in 2003. SETTING: Participants were recruited from the Qingdao Twin Registry, a school-based registry. PARTICIPANTS: A total of 360 twin girls aged 6-18 yr were enrolled, consisting of 132 pairs of monozygotic and 48 pairs of dizygotic twins. INTERVENTIONS: Anthropometric and sexual characteristics were examined. Serum total leptin and free IGF-I were measured by immunoradiometric assay, and SOB-R was measured by ELISA. MAIN OUTCOME MEASURE: Estimates of genetic and environmental components of variance were based on the theory of normal maximum likelihood in Mx package, a computer program specifically designed for the analysis of twin and family data. RESULTS: Serum leptin concentrations increased persistently throughout puberty, especially from Tanner stage III to Tanner stage IV (P < 0.05), which in consistent with the increase of percentage of body fat. However, SOB-R decreased significantly from Tanner stage I to Tanner stage II (P < 0.05), which results in a continuous rise of FLI (ratio of leptin to SOB-R), especially from Tanner stage I to Tanner stage II (P < 0.05). Serum free IGF-I increased dramatically from Tanner stage I to II and declined since then. Results of correlation analysis suggest that FLI predicts the pubertal growth and sexual maturation more effectively, whereas leptin sensitively reflects the fat mass of body composition. Quantitative genetic model fittings showed that SOB-R and free IGF-I have higher heritability (0.62-0.77, 0.54-0.66) and leptin and FLI have lower heritability (0.38-0.48, 0.44-0.55). CONCLUSIONS: Fast increase of FLI and free IGF-I from Tanner stage I to II might be involved in the onset of puberty and the onset of thelarche. The peak of free IGF-I in Tanner stage II might be presumed as an indicator of the peak of pubertal growth spurt in females, and the significant rise of leptin along with percentage of body fat from Tanner stage III to IV might be as a predictor of the forthcoming menarche. Our results stress the importance of research into the genetic regulation on the endocrine regulators involved in the pubertal development and metabolic disorders, including pubertal obesity and diabetes.

Adolescent↗

Testing a model of aging in animal experiments.

A stochastic model of aging is developed in terms of accumulation and expression of intracellular lesions caused by environment or intrinsic genetic program. In contrast to the commonly used Gompertz-Makeham approach to the parametric analysis of mortality data, the model yields a hazard function that is bounded from above. For testing the model in experiments aimed at studying animal longevity, a Kolmogorov-type statistical test is presented with regard to the hypothesis involving unknown parameters. Examples concerning longevity of intact animals of two different species, as well as the effect of a prolonged irradiation at a low dose rate, are given to illustrate the model application and goodness-of-fit testing. The results of the analysis of published data show that the rate of lesion formation is not sustained at a constant level throughout life, though in some cases its variations with age can be considered negligible.

Aging↗

Recent progress in livestock genomics and potential impact on breeding programs.

Most of the major livestock breeding organizations in the world are actively involved in using the emerging tools for genome analysis to obtain a better understanding of the molecular architecture of their favourite production traits. This is bound to generate a considerable amount of novel biological information that will provide a competitive advantage to those that have access to it. At present, the preferred avenue to exploit this information is via marker-assisted selection (MAS), and several breeding organisations are starting to implement MAS in breeding programs. However, it seems unlikely that the exploitation of genomics information will be limited to MAS in the future. Even though it is difficult to anticipate the ultimate impact of genomics on animal production, it would be very surprising if it were not to revolutionize this industry as it is already revolutionizing the biomedical and plant breeding industries.

Animals↗

Quantitative computer analysis of signal sequence homologies in DNA.

Homologies to prokaryotic recognition sites for RNA polymerase, ribosomes, and cyclic-AMP receptor protein (CRP), are analyzed by a new computer program using weighting factors to account for the statistical variation at each position of the consensus. Known signal sequence sites are easily detected by this algorithm, and other sites with equally strong homology are found whose biological function is still unknown. Some sites are biologically active even though they have very weak homology. No arbitrary 'cutoff score' can distinguish active recognition sites from inactive homologies; experiments must determine why certain weak homologies are able to function while others are not.

Algorithms↗