Genetic Variation: Genotypic differences observed among individuals in a population.Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Genetics, Population: The discipline studying genetic composition of populations and effects of factors such as GENETIC SELECTION, population size, MUTATION, migration, and GENETIC DRIFT on the frequencies of various GENOTYPES and PHENOTYPES using a variety of GENETIC TECHNIQUES.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Geography: The science dealing with the earth and its life, especially the description of land, sea, and air and the distribution of plant and animal life, including humanity and human industries with reference to the mutual relations of these elements. (From Webster, 3d ed)Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Quantitative Trait Loci: Genetic loci associated with a QUANTITATIVE TRAIT.Genetic Association Studies: The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.Biological Evolution: The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Genome-Wide Association Study: An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.Genetic Loci: Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.Quantitative Trait, Heritable: A characteristic showing quantitative inheritance such as SKIN PIGMENTATION in humans. (From A Dictionary of Genetics, 4th ed)Pharmacogenetics: A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).DNA Copy Number Variations: Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Gene Flow: The change in gene frequency in a population due to migration of gametes or individuals (ANIMAL MIGRATION) across population barriers. In contrast, in GENETIC DRIFT the cause of gene frequency changes are not a result of population or gamete movement.INDEL Mutation: A mutation named with the blend of insertion and deletion. It refers to a length difference between two ALLELES where it is unknowable if the difference was originally caused by a SEQUENCE INSERTION or by a SEQUENCE DELETION. If the number of nucleotides in the insertion/deletion is not divisible by three, and it occurs in a protein coding region, it is also a FRAMESHIFT MUTATION.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.Crosses, Genetic: Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.European Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Europe.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Antigenic Variation: Change in the surface ANTIGEN of a microorganism. There are two different types. One is a phenomenon, especially associated with INFLUENZA VIRUSES, where they undergo spontaneous variation both as slow antigenic drift and sudden emergence of new strains (antigenic shift). The second type is when certain PARASITES, especially trypanosomes, PLASMODIUM, and BORRELIA, survive the immune response of the host by changing the surface coat (antigen switching). (From Herbert et al., The Dictionary of Immunology, 4th ed)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Inbreeding: The mating of plants or non-human animals which are closely related genetically.Genetic Drift: The fluctuation of the ALLELE FREQUENCY from one generation to the next.Asian Continental Ancestry Group: Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.Phylogeography: A field of study concerned with the principles and processes governing the geographic distributions of genealogical lineages, especially those within and among closely related species. (Avise, J.C., Phylogeography: The History and Formation of Species. Harvard University Press, 2000)Environment: The external elements and conditions which surround, influence, and affect the life and development of an organism or population.Breeding: The production of offspring by selective mating or HYBRIDIZATION, GENETIC in animals or plants.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Epistasis, Genetic: A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.Random Amplified Polymorphic DNA Technique: Technique that utilizes low-stringency polymerase chain reaction (PCR) amplification with single primers of arbitrary sequence to generate strain-specific arrays of anonymous DNA fragments. RAPD technique may be used to determine taxonomic identity, assess kinship relationships, analyze mixed genome samples, and create specific probes.China: A country spanning from central Asia to the Pacific Ocean.Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population.Inheritance Patterns: The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION.Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.Population Density: Number of individuals in a population relative to space.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Principal Component Analysis: Mathematical procedure that transforms a number of possibly correlated variables into a smaller number of uncorrelated variables called principal components.Ecosystem: A functional system which includes the organisms of a natural community together with their environment. (McGraw Hill Dictionary of Scientific and Technical Terms, 4th ed)Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with well-defined distribution patterns in relation to time or place or both.Homozygote: An individual in which both alleles at a given locus are identical.Hybridization, Genetic: The genetic process of crossbreeding between genetically dissimilar parents to produce a hybrid.Reproduction: The total process by which organisms produce offspring. (Stedman, 25th ed)Seasons: Divisions of the year according to some regularly recurrent phenomena usually astronomical or climatic. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Adaptation, Biological: Changes in biological features that help an organism cope with its ENVIRONMENT. These changes include physiological (ADAPTATION, PHYSIOLOGICAL), phenotypic and genetic changes.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Mimulus: A plant genus of the family Phrymaceae. Members contain 6-geranylflavanones and mimulone.EuropeAdaptation, Physiological: The non-genetic biological changes of an organism in response to challenges in its ENVIRONMENT.Genome: The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.Gene-Environment Interaction: The combined effects of genotypes and environmental factors together on phenotypic characteristics.Population: The total number of individuals inhabiting a particular region or area.Amplified Fragment Length Polymorphism Analysis: The detection of RESTRICTION FRAGMENT LENGTH POLYMORPHISMS by selective PCR amplification of restriction fragments derived from genomic DNA followed by electrophoretic analysis of the amplified restriction fragments.Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.Multifactorial Inheritance: A phenotypic outcome (physical characteristic or disease predisposition) that is determined by more than one gene. Polygenic refers to those determined by many genes, while oligogenic refers to those determined by a few genes.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships.Catechol O-Methyltransferase: Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Bayes Theorem: A theorem in probability theory named for Thomas Bayes (1702-1761). In epidemiology, it is used to obtain the probability of disease in a group of people with some characteristic on the basis of the overall rate of that disease and of the likelihood of that characteristic in healthy and diseased individuals. The most familiar application is in clinical decision analysis where it is used for estimating the probability of a particular diagnosis given the appearance of some symptoms or test result.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Genomic Structural Variation: Contiguous large-scale (1000-400,000 basepairs) differences in the genomic DNA between individuals, due to SEQUENCE DELETION; SEQUENCE INSERTION; or SEQUENCE INVERSION.Genotyping Techniques: Methods used to determine individuals' specific ALLELES or SNPS (single nucleotide polymorphisms).Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Endangered Species: An animal or plant species in danger of extinction. Causes can include human activity, changing climate, or change in predator/prey ratios.Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches.Genetic Structures: The biological objects that contain genetic information and that are involved in transmitting genetically encoded traits from one organism to another.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Time Factors: Elements of limited time intervals, contributing to particular results or situations.DNA, Plant: Deoxyribonucleic acid that makes up the genetic material of plants.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Genome, Plant: The genetic complement of a plant (PLANTS) as represented in its DNA.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Mating Preference, Animal: The selection or choice of sexual partner in animals. Often this reproductive preference is based on traits in the potential mate, such as coloration, size, or behavioral boldness. If the chosen ones are genetically different from the rejected ones, then NATURAL SELECTION is occurring.Genetic Fitness: The capability of an organism to survive and reproduce. The phenotypic expression of the genotype in a particular environment determines how genetically fit an organism will be.African Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Africa.Body Size: The physical measurements of a body.Islands: Tracts of land completely surrounded by water.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.Genetic Speciation: The splitting of an ancestral species into daughter species that coexist in time (King, Dictionary of Genetics, 6th ed). Causal factors may include geographic isolation, HABITAT geometry, migration, REPRODUCTIVE ISOLATION, random GENETIC DRIFT and MUTATION.DNA, Chloroplast: Deoxyribonucleic acid that makes up the genetic material of CHLOROPLASTS.AfricaComputer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Animals, Inbred Strains: Animals produced by the mating of progeny over multiple generations. The resultant strain of animals is virtually identical genotypically. Highly inbred animal lines allow the study of certain traits in a relatively pure form. (Segen, Dictionary of Modern Medicine, 1992)Genetic Pleiotropy: A phenomenon in which multiple and diverse phenotypic outcomes are influenced by a single gene (or single gene product.)Demography: Statistical interpretation and description of a population with reference to distribution, composition, or structure.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Gene Dosage: The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.HapMap Project: A coordinated international effort to identify and catalog patterns of linked variations (HAPLOTYPES) found in the human genome across the entire human population.Sexual Behavior, Animal: Sexual activities of animals.Risk: The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome.Ecology: The branch of science concerned with the interrelationship of organisms and their ENVIRONMENT, especially as manifested by natural cycles and rhythms, community development and structure, interactions between different kinds of organisms, geographic distributions, and population alterations. (Webster's, 3d ed)Pinus: A plant genus in the family PINACEAE, order Pinales, class Pinopsida, division Coniferophyta. They are evergreen trees mainly in temperate climates.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Climate: The longterm manifestations of WEATHER. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Models, Statistical: Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.Chromosomes, Human, Y: The human male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans.Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters.Genealogy and HeraldryGenes, Plant: The functional hereditary units of PLANTS.Flowers: The reproductive organs of plants.Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable.Fertility: The capacity to conceive or to induce conception. It may refer to either the male or female.High-Throughput Nucleotide Sequencing: Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc.Host-Parasite Interactions: The relationship between an invertebrate and another organism (the host), one of which lives at the expense of the other. Traditionally excluded from definition of parasites are pathogenic BACTERIA; FUNGI; VIRUSES; and PLANTS; though they may live parasitically.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Sex Characteristics: Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction.Genes, Insect: The functional hereditary units of INSECTS.Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression.Population Groups: Individuals classified according to their sex, racial origin, religion, common place of living, financial or social status, or some other cultural or behavioral attribute. (UMLS, 2003)Minisatellite Repeats: Tandem arrays of moderately repetitive, short (10-60 bases) DNA sequences which are found dispersed throughout the GENOME, at the ends of chromosomes (TELOMERES), and clustered near telomeres. Their degree of repetition is two to several hundred at each locus. Loci number in the thousands but each locus shows a distinctive repeat unit.Serotonin Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SEROTONIN UPTAKE INHIBITORS.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)Cytochromes b: Cytochromes of the b group that have alpha-band absorption of 563-564 nm. They occur as subunits in MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III.Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, and feeding.IndiaConservation of Natural Resources: The protection, preservation, restoration, and rational use of all resources in the total environment.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Observer Variation: The failure by the observer to measure or identify a phenomenon accurately, which results in an error. Sources for this may be due to the observer's missing an abnormality, or to faulty technique resulting in incorrect test measurement, or to misinterpretation of the data. Two varieties are inter-observer variation (the amount observers vary from one another when reporting on the same material) and intra-observer variation (the amount one observer varies between observations when reporting more than once on the same material).United StatesButterflies: Slender-bodies diurnal insects having large, broad wings often strikingly colored and patterned.Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases.Nutrigenomics: The study of the relationship between NUTRITIONAL PHYSIOLOGY and genetic makeup. It includes the effect of different food components on GENE EXPRESSION and how variations in GENES effect responses to food components.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Ecotype: Geographic variety, population, or race, within a species, that is genetically adapted to a particular habitat. An ecotype typically exhibits phenotypic differences but is capable of interbreeding with other ecotypes.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Plant Leaves: Expanded structures, usually green, of vascular plants, characteristically consisting of a bladelike expansion attached to a stem, and functioning as the principal organ of photosynthesis and transpiration. (American Heritage Dictionary, 2d ed)Pan troglodytes: The common chimpanzee, a species of the genus Pan, family HOMINIDAE. It lives in Africa, primarily in the tropical rainforests. There are a number of recognized subspecies.Smegmamorpha: Group of fish under the superorder Acanthopterygii, separate from the PERCIFORMES, which includes swamp eels, mullets, sticklebacks, seahorses, spiny eels, rainbowfishes, and KILLIFISHES. The name is derived from the six taxa which comprise the group. (From http://www.nanfa.org/articles/Elassoma/elassoma.htm, 8/4/2000)Sex Factors: Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances.Cistus: A plant genus of the family CISTACEAE. The common name of rock rose is also sometimes used with the closely related Helianthemum genus (CISTACEAE).Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Pigmentation: Coloration or discoloration of a part by a pigment.Heredity: The transmission of traits encoded in GENES from parent to offspring.Genetic Heterogeneity: The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)JapanAfrican Americans: Persons living in the United States having origins in any of the black groups of Africa.Dalbergia: A plant genus of the family FABACEAE. Members of this genus can cause CONTACT DERMATITIS.Seeds: The encapsulated embryos of flowering plants. They are used as is or for animal feed because of the high content of concentrated nutrients like starches, proteins, and fats. Rapeseed, cottonseed, and sunflower seed are also produced for the oils (fats) they yield.Daphnia: A diverse genus of minute freshwater CRUSTACEA, of the suborder CLADOCERA. They are a major food source for both young and adult freshwater fish.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Quercus: A plant genus of the family FAGACEAE that is a source of TANNINS. Do not confuse with Holly (ILEX).Genetics, Medical: A subdiscipline of human genetics which entails the reliable prediction of certain human disorders as a function of the lineage and/or genetic makeup of an individual or of any two parents or potential parents.Asia: The largest of the continents. It was known to the Romans more specifically as what we know today as Asia Minor. The name comes from at least two possible sources: from the Assyrian asu (to rise) or from the Sanskrit usa (dawn), both with reference to its being the land of the rising sun, i.e., eastern as opposed to Europe, to the west. (From Webster's New Geographical Dictionary, 1988, p82 & Room, Brewer's Dictionary of Names, 1992, p34)South AmericaTemperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Genetic Diseases, Inborn: Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.Longevity: The normal length of time of an organism's life.Mutation Rate: The number of mutations that occur in a specific sequence, GENE, or GENOME over a specified period of time such as years, CELL DIVISIONS, or generations.Continental Population Groups: Groups of individuals whose putative ancestry is from native continental populations based on similarities in physical appearance.Chromosomes: In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)DNA, Ribosomal Spacer: The intergenic DNA segments that are between the ribosomal RNA genes (internal transcribed spacers) and between the tandemly repeated units of rDNA (external transcribed spacers and nontranscribed spacers).Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Animals, Wild: Animals considered to be wild or feral or not adapted for domestic use. It does not include wild animals in zoos for which ANIMALS, ZOO is available.Beetles: INSECTS of the order Coleoptera, containing over 350,000 species in 150 families. They possess hard bodies and their mouthparts are adapted for chewing.Human Genome Project: A coordinated effort of researchers to map (CHROMOSOME MAPPING) and sequence (SEQUENCE ANALYSIS, DNA) the human GENOME.Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.DNA Fingerprinting: A technique for identifying individuals of a species that is based on the uniqueness of their DNA sequence. Uniqueness is determined by identifying which combination of allelic variations occur in the individual at a statistically relevant number of different loci. In forensic studies, RESTRICTION FRAGMENT LENGTH POLYMORPHISM of multiple, highly polymorphic VNTR LOCI or MICROSATELLITE REPEAT loci are analyzed. The number of loci used for the profile depends on the ALLELE FREQUENCY in the population.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)LizardsCentral AmericaGene Pool: The total genetic information possessed by the reproductive members of a POPULATION of sexually reproducing organisms.Exome: That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Genome, Insect: The genetic complement of an insect (INSECTS) as represented in its DNA.5' Flanking Region: The region of DNA which borders the 5' end of a transcription unit and where a variety of regulatory sequences are located.Costa RicaPanamaEnzymes: Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.Chromosomes, Plant: Complex nucleoprotein structures which contain the genomic DNA and are part of the CELL NUCLEUS of PLANTS.
Genetic variation: right|thumbWGAViewer: WGAViewer is a bioinformatics software tool which is designed to visualize, annotate, and help interpret the results generated from a genome wide association study (GWAS). Alongside the P values of association, WGAViewer allows a researcher to visualize and consider other supporting evidence, such as the genomic context of the SNP, linkage disequilibrium (LD) with ungenotyped SNPs, gene expression database, and the evidence from other GWAS projects, when determining the potential importance of an individual SNP.Gene polymorphismPanmixia: Panmixia (or panmixis) means random mating.King C and Stanfield W.Infinite alleles model: The infinite alleles model is a mathematical model for calculating genetic mutations. The Japanese geneticist Motoo Kimura and American geneticist James F.Disequilibrium (medicine): Disequilibrium}}Phenotype microarray: The phenotype microarray approach is a technology for high-throughput phenotyping of cells.Branching order of bacterial phyla (Gupta, 2001): There are several models of the Branching order of bacterial phyla, one of these was proposed in 2001 by Gupta based on conserved indels or protein, termed "protein signatures", an alternative approach to molecular phylogeny. Some problematic exceptions and conflicts are present to these conserved indels, however, they are in agreement with several groupings of classes and phyla.Selection (relational algebra): In relational algebra, a selection (sometimes called a restriction to avoid confusion with SQL's use of SELECT) is a unary operation written asDNA sequencer: A DNA sequencer is a scientific instrument used to automate the DNA sequencing process. Given a sample of DNA, a DNA sequencer is used to determine the order of the four bases: G (guanine), C (cytosine), A (adenine) and T (thymine).Health geography: Health geography is the application of geographical information, perspectives, and methods to the study of health, disease, and health care.Microsatellite: A microsatellite is a tract of repetitive DNA in which certain DNA motifs (ranging in length from 2–5 base pairs) are repeated, typically 5-50 times. Microsatellites occur at thousands of locations in the human genome and they are notable for their high mutation rate and high diversity in the population.Nested case-control study: A nested case control (NCC) study is a variation of a case-control study in which only a subset of controls from the cohort are compared to the incident cases. In a case-cohort study, all incident cases in the cohort are compared to a random subset of participants who do not develop the disease of interest.Coles PhillipsMolecular evolution: Molecular evolution is a change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes.Symmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.Population stratification: Population stratification is the presence of a systematic difference in allele frequencies between subpopulations in a population possibly due to different ancestry, especially in the context of association studies. Population stratification is also referred to as population structure, in this context.Pharmacogenetics: Pharmacogenetics is the study of inherited genetic differences in drug metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects. The term pharmacogenetics is often used interchangeably with the term pharmacogenomics which also investigates the role of acquired and inherited genetic differences in relation to drug response and drug behavior through a systematic examination of genes, gene products, and inter- and intra-individual variation in gene expression and function.Chromosome regionsHaplogroup L0 (mtDNA)Thermal cyclerAntigenic shiftSilent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.Inbreeding depression: Inbreeding depression is the reduced biological fitness in a given population as a result of inbreeding, or breeding of related individuals. Population biological fitness refers to its ability to survive and reproduce itself.Microevolution: Microevolution is the change in allele frequencies that occur over time within a population.Microevolution: What is microevolution?Phylogeography: Phylogeography is the study of the historical processes that may be responsible for the contemporary geographic distributions of individuals. This is accomplished by considering the geographic distribution of individuals in light of the patterns associated with a gene genealogy.Evolution in Variable EnvironmentPlant breedingQRISK: QRISK2 (the most recent version of QRISK) is a prediction algorithm for cardiovascular disease (CVD) that uses traditional risk factors (age, systolic blood pressure, smoking status and ratio of total serum cholesterol to high-density lipoprotein cholesterol) together with body mass index, ethnicity, measures of deprivation, family history, chronic kidney disease, rheumatoid arthritis, atrial fibrillation, diabetes mellitus, and antihypertensive treatment.Ontario Genomics Institute: The Ontario Genomics Institute (OGI) is a not-for-profit organization that manages cutting-edge genomics research projects and platforms.The Ontario Genomics Institute OGI also helps scientists find paths to the marketplace for their discoveries and the products to which they lead, and it works through diverse outreach and educational activities to raise awareness and facilitate informed public dialogue about genomics and its social impacts.RAPD: RAPD (pronounced "rapid") stands for 'Random Amplified Polymorphic DNA'. It is a type of PCR reaction, but the segments of DNA that are amplified are random.Layout of the Port of Tianjin: The Port of Tianjin is divided into nine areas: the three core (“Tianjin Xingang”) areas of Beijiang, Nanjiang, and Dongjiang around the Xingang fairway; the Haihe area along the river; the Beitang port area around the Beitangkou estuary; the Dagukou port area in the estuary of the Haihe River; and three areas under construction (Hanggu, Gaoshaling, Nangang).Matrix population models: Population models are used in population ecology to model the dynamics of wildlife or human populations. Matrix population models are a specific type of population model that uses matrix algebra.Uniparental inheritance: Uniparental inheritance is a non-mendelian form of inheritance that consists of the transmission of genotypes from one parental type to all progeny. That is, all the genes in offspring will originate from only the mother or only the father.Amplified fragment length polymorphismThreshold host density: Threshold host density (NT), in the context of wildlife disease ecology, refers to the concentration of a population of a particular organism as it relates to disease. Specifically, the threshold host density (NT) of a species refers to the minimum concentration of individuals necessary to sustain a given disease within a population.Genetic linkage: Genetic linkage is the tendency of alleles that are located close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Genes whose loci are nearer to each other are less likely to be separated onto different chromatids during chromosomal crossover, and are therefore said to be genetically linked.RV coefficient: In statistics, the RV coefficientEcosystemHybrid inviability: Hybrid inviability is a post-zygotic barrier, which reduces a hybrid's capacity to mature into a healthy, fit adult.Hybrid inviability.Reproductive toxicity: Reproductive toxicity is a hazard associated with some chemical substances, that they will interfere in some way with normal reproduction; such substances are called reprotoxic. It includes adverse effects on sexual function and fertility in adult males and females, as well as developmental toxicity in the offspring.Four Seasons Baltimore and Residences: Four Seasons Hotel Baltimore is currently a 22 story highrise hotel complex building which opened on November 14, 2011. The building's construction began back in 2007 and went through several changes.Indy (gene): Indy, short for I'm not dead yet, is a gene of the model organism, the fruit fly Drosophila melanogaster. Mutant versions of this gene have doubled the average life span of fruit flies in at least one set of experiments, but this result has been subject to controversy.Recombination (cosmology): In cosmology, recombination refers to the epoch at which charged electrons and protons first became bound to form electrically neutral hydrogen atoms.Note that the term recombination is a misnomer, considering that it represents the first time that electrically neutral hydrogen formed.GA²LENMaladaptation: A maladaptation () is a trait that is (or has become) more harmful than helpful, in contrast with an adaptation, which is more helpful than harmful. All organisms, from bacteria to humans, display maladaptive and adaptive traits.List of sequenced eukaryotic genomesGeneralizability theory: Generalizability theory, or G Theory, is a statistical framework for conceptualizing, investigating, and designing reliable observations. It is used to determine the reliability (i.Extracellular: In cell biology, molecular biology and related fields, the word extracellular (or sometimes extracellular space) means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid.Hyperparameter: In Bayesian statistics, a hyperparameter is a parameter of a prior distribution; the term is used to distinguish them from parameters of the model for the underlying system under analysis.Clonal Selection Algorithm: In artificial immune systems, Clonal selection algorithms are a class of algorithms inspired by the clonal selection theory of acquired immunity that explains how B and T lymphocytes improve their response to antigens over time called affinity maturation. These algorithms focus on the Darwinian attributes of the theory where selection is inspired by the affinity of antigen-antibody interactions, reproduction is inspired by cell division, and variation is inspired by somatic hypermutation.Alternative splicing: Alternative splicing is a regulated process during gene expression that results in a single gene coding for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene.Peat swamp forest: Peat swamp forests are tropical moist forests where waterlogged soil prevents dead leaves and wood from fully decomposing. Over time, this creates a thick layer of acidic peat.Genetic structure: Genetic structure refers to any pattern in the genetic makeup of individuals within a population.CS-BLASTTemporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingDNA condensation: DNA condensation refers to the process of compacting DNA molecules in vitro or in vivo. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems.Protein primary structure: The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end.Biological ornament: A biological ornament is a secondary sexual characteristic of an animal that appears to serve a decorative function rather than an ostensible, utilitarian function. Ornaments are used in displays to attract mates in a process known as sexual selection.
(1/30484) Hidden genetic variability within electromorphs in finite populations.
The amount of hidden genetic variability within electromorphs in finite populations is studied by using the infinite site model and stepwise mutation model simultaneously. A formula is developed for the bivariate probability generating function for the number of codon differences and the number of electromorph state differences between two randomly chosen cistrons. Using this formula, the distribution as well as the mean and variance of the number of codon differences between two identical or nonidentical electromorphs are studied. The distribution of the number of codon differences between two randomly chosen identical electromorphs is similar to the geometric distribution but more leptokurtic. Studies are also made on the number of codon differences between two electromorphs chosen at random one from each of two populations which have been separated for an arbitrary number of generations. It is shown that the amount of hidden genetic variability is very large if the product of effective population size and mutation rate is large. (+info)
(2/30484) The Lewontin and Krakauer test on quantitative characters.
It is shown that LEWONTIN and KRAKAUER's test could also be applied to quantitative characters that do not show important dominance and epistatic genetic variances. The design of experiments for this purpose and the error of the estimation of F are discussed. (+info)
(3/30484) Expression of the naturally occurring truncated trkB neurotrophin receptor induces outgrowth of filopodia and processes in neuroblastoma cells.
We have investigated the effects of the truncated trkB receptor isoform T1 (trkB.T1) by transient transfection into mouse N2a neuroblastoma cells. We observed that expression of trkB.T1 leads to a striking change in cell morphology characterized by outgrowth of filopodia and processes. A similar morphological response was also observed in SH-SY5Y human neuroblastoma cells and NIH3T3 fibroblasts transfected with trkB.T1. N2a cells lack endogenous expression of trkB isoforms, but express barely detectable amounts of its ligands, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). The morphological change was ligand-independent, since addition of exogenous BDNF or NT-4 or blockade of endogenous trkB ligands did not influence this response. Filopodia and process outgrowth was significantly suppressed when full-length trkB.TK+ was cotransfected together with trkB.T1 and this inhibitory effect was blocked by tyrosine kinase inhibitor K252a. Transfection of trkB.T1 deletion mutants showed that the morphological response is dependent on the extracellular, but not the intracellular domain of the receptor. Our results suggest a novel ligand-independent role for truncated trkB in the regulation of cellular morphology. (+info)
(4/30484) Over-representation of a germline RET sequence variant in patients with sporadic medullary thyroid carcinoma and somatic RET codon 918 mutation.
The aetiology of sporadic medullary thyroid carcinoma is unknown. About 50% harbour a somatic mutation at codon 918 of RET (M918T). To investigate whether other RET sequence variants may be associated with or predispose to the development of sporadic medullary thyroid carcinoma, we analysed genomic DNA from the germline and corresponding tumour from 50 patients to identify RET sequence variants. In one patient, tumour DNA showed a novel somatic 12 bp in-frame deletion in exon 15. More interestingly, we found that the rare polymorphism at codon 836 (c.2439C > T; S836S) occurred at a significantly higher frequency than that in control individuals without sporadic medullary thyroid carcinoma (Fisher's exact test, P = 0.03). Further, among the nine evaluable cases with germline c.2439C/T, eight also had the somatic M918T mutation in MTC DNA which was more frequent than in patients with the more common c.2439C/C (89% vs 40%, respectively; Fisher's exact test, P = 0.01). These findings suggest that the rare sequence variant at codon 836 may somehow play a role in the genesis of sporadic medullary thyroid carcinoma. (+info)
(5/30484) The nuclear receptor superfamily has undergone extensive proliferation and diversification in nematodes.
The nuclear receptor (NR) superfamily is the most abundant class of transcriptional regulators encoded in the Caenorhabditis elegans genome, with >200 predicted genes revealed by the screens and analysis of genomic sequence reported here. This is the largest number of NR genes yet described from a single species, although our analysis of available genomic sequence from the related nematode Caenorhabditis briggsae indicates that it also has a large number. Existing data demonstrate expression for 25% of the C. elegans NR sequences. Sequence conservation and statistical arguments suggest that the majority represent functional genes. An analysis of these genes based on the DNA-binding domain motif revealed that several NR classes conserved in both vertebrates and insects are also represented among the nematode genes, consistent with the existence of ancient NR classes shared among most, and perhaps all, metazoans. Most of the nematode NR sequences, however, are distinct from those currently known in other phyla, and reveal a previously unobserved diversity within the NR superfamily. In C. elegans, extensive proliferation and diversification of NR sequences have occurred on chromosome V, accounting for > 50% of the predicted NR genes. (+info)
(6/30484) Hemoglobin Providence. A human hemoglobin variant occurring in two forms in vivo.
Hemoglobin Providence Asn and Hemoglobin Providence Asp are two abnormal hemoglobins which apparently arise from a single genetic change that substitutes asparagine for lysine at position 82 (EF6) in the beta chain of human hemoglobin. The second form appears to be thr result of a partial in vivo deamidation of the asparagine situated at position beta 82. Cellulose acetate and citrate agar electrophoresis of hemolysates from patients with this abnormality shows three bands. Globin chain electrophoresis at acid and alkaline pH shows three beta chains. These three chains correspond to the normal beta A chain and two abnormal beta chains. Sequence analysis indicates that the two abnormal chains differ from beta A at only position beta 82. In the two abnormal chains, the residue which is normally lysine is substituted either by asparagine or by aspartic acid. These substitutions are notable because beta 82 lysine is one of the residues involved in 2,3-diphosphoglycerate binding. Additionally, beta 82 lysine is typically invariant in hemoglobin beta chain sequences. Sequence data on the two forms of Hemoglobin Providence are given in this paper. The functional properties of these two forms are described in the next paper. (+info)
(7/30484) Isolation and characterization of two mouse L cell lines resistant to the toxic lectin ricin.
Two variant mouse L cell lines (termed CL 3 and CL 6) have been selected for resistant to ricin, a galactose-binding lectin with potent cytotoxic activity. The resistant lines exhibit a 50 to 70% decrease in ricin binding and a 300- to 500-fold increase in resistance to the toxic effects of ricin. Crude membrane preparations of CL 3 cells have increased sialic acid content (200% of control), while the galactose, mannose, and hexosamine content is within normal limits. Both the glycoproteins and glycolipids of CL 3 cells have increased sialic acid, with the GM3:lactosylceramide ratios for parent L and CL 3 cells being 0.29 and 1.5, respectively. In contrast, the membranes of CL 6 cells have a decrease in sialic acid, galactose, and hexosamine content with mannose being normal. Both cell lines have specific alterations in glycosyltransferase activities which can account for the observed membrane sugar changes. CL 3 cells have increased CMP-sialic acid:glycoprotein sialyltransferase and GM3 synthetase activities, while CL 6 cells have decrease UDP-GlcNAc:glycoproteinN-acetylglucosaminyltransferase and DPU-galactose:glycoprotein galactosyltransferase activities. The increased sialic acid content of CL 3 cells serves to mask ricin binding sites, since neuraminidase treatment of this cell line restores ricin binding to essentially normal levels. However, the fact that neuraminidase-treated CL 3 cells are still 45-fold resistant to ricin indicates that either a special class of productive ricin binding sites is not being exposed or that the cell line has a second mechanism for ricin resistance. (+info)
(8/30484) Constitutional genetic variation at the human aromatase gene (Cyp19) and breast cancer risk.
The activity of the aromatase enzyme, which converts androgens into oestrogens and has a major role in regulating oestrogen levels in the breast, is thought to be a contributing factor in the development of breast cancer. We undertook this study to assess the role of constitutional genetic variation in the human aromatase gene (Cyp19) in the development of this disease. Our genotyping of 348 cases with breast cancer and 145 controls (all Caucasian women) for a published tetranucleotide repeat polymorphism at intron 4 of the Cyp19 gene revealed the presence of six common and two rare alleles. Contingency table analysis revealed a significant difference in allelic distribution between cases and controls (chi2 5df = 13.52, P = 0.019). The allele measuring 171 bp was over-represented in cases; of 14 individuals homozygous for this allele, 13 were cases. These individuals had a higher incidence of cancer in family members and an earlier age at diagnosis than other cases. In sequencing Cyp19's coding exons and regulatory regions, we discovered a perfect association between a silent polymorphism (G-->A at Val80) and the high-risk genotype. Our conclusion is that constitutional genetic variation at the Cyp19 locus is associated with the risk of developing breast cancer, with the 171-bp allele serving as the high-risk allele. (+info)