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)
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.
The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.
The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds."
Genotypic differences observed among individuals in a population.
Any method used for determining the location of and relative distances between genes on a chromosome.
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.
Genes that influence the PHENOTYPE only in the homozygous state.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
The magnitude of INBREEDING in humans.
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.
A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.
Biochemical identification of mutational changes in a nucleotide sequence.
That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.
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).
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.
A characteristic symptom complex.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
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.
A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
An individual in which both alleles at a given locus are identical.
The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)
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.
A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.
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.
The relationships of groups of organisms as reflected by their genetic makeup.
Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.
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.
One of the two pairs of human chromosomes in the group B class (CHROMOSOMES, HUMAN, 4-5).
The age, developmental stage, or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual.
A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
A specific pair GROUP C CHROMSOMES of the human chromosome classification.
An individual having different alleles at one or more loci regarding a specific character.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
An autosomal recessive disorder characterized by RETINITIS PIGMENTOSA; POLYDACTYLY; OBESITY; MENTAL RETARDATION; hypogenitalism; renal dysplasia; and short stature. This syndrome has been distinguished as a separate entity from LAURENCE-MOON SYNDROME. (From J Med Genet 1997 Feb;34(2):92-8)
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.
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.
The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.
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)
A statistical tool for detecting and modeling gene-gene interactions. It is a non-parametric and model-free approach.
Brain tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur.
Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.
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.
A specific pair of GROUP C CHROMSOMES of the human chromosome classification.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A social group consisting of parents or parent substitutes and children.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
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.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
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).
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
A general term for the complete loss of the ability to hear from both ears.
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.
Individual members of South American ethnic groups with historic ancestral origins in Asia.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)
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.
An autosomal inherited disorder due to defective reabsorption of GLUCOSE by the PROXIMAL RENAL TUBULES. The urinary loss of glucose can reach beyond 50 g/day. It is attributed to the mutations in the SODIUM-GLUCOSE TRANSPORTER 2 encoded by the SLC5A2 gene.
A relatively rare smooth muscle tumor found most frequently in the wall of the gastrointestinal tract, especially in the stomach. It is similar to other smooth muscle tumors but may become very large and hemorrhage and exhibit small cystic areas. Simple excision is almost always curative. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1354)
A group of slowly progressive inherited disorders affecting motor and sensory peripheral nerves. Subtypes include HMSNs I-VII. HMSN I and II both refer to CHARCOT-MARIE-TOOTH DISEASE. HMSN III refers to hypertrophic neuropathy of infancy. HMSN IV refers to REFSUM DISEASE. HMSN V refers to a condition marked by a hereditary motor and sensory neuropathy associated with spastic paraplegia (see SPASTIC PARAPLEGIA, HEREDITARY). HMSN VI refers to HMSN associated with an inherited optic atrophy (OPTIC ATROPHIES, HEREDITARY), and HMSN VII refers to HMSN associated with retinitis pigmentosa. (From Adams et al., Principles of Neurology, 6th ed, p1343)
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.
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.
An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.
A form of congenital ichthyosis inherited as an autosomal dominant trait and characterized by ERYTHRODERMA and severe hyperkeratosis. It is manifested at birth by blisters followed by the appearance of thickened, horny, verruciform scales over the entire body, but accentuated in flexural areas. Mutations in the genes that encode KERATIN-1 and KERATIN-10 have been associated with this disorder.
Identification of genetic carriers for a given trait.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
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.
Abnormal development of cartilage and bone.
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
A chromosomal disorder characterized by MENTAL RETARDATION, broad thumbs, webbing of fingers and toes, beaked nose, short upper lip, pouting lower lip, agenesis of corpus callosum, large foramen magnum, keloid formation, pulmonary stenosis, vertebral anomalies, chest wall anomalies, sleep apnea, and megacolon. The disease has an autosomal dominant pattern of inheritance and is associated with deletions of the short arm of chromosome 16 (16p13.3).
A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.
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.
Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.
An inherited disorder due to defective reabsorption of CYSTINE and other BASIC AMINO ACIDS by the PROXIMAL RENAL TUBULES. This form of aminoaciduria is characterized by the abnormally high urinary levels of cystine; LYSINE; ARGININE; and ORNITHINE. Mutations involve the amino acid transport protein gene SLC3A1.
Electrophoresis in which a starch gel (a mixture of amylose and amylopectin) is used as the diffusion medium.
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.
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.
Congenital absence of or defects in structures of the eye; may also be hereditary.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.
Hereditary conditions that feature progressive visual loss in association with optic atrophy. Relatively common forms include autosomal dominant optic atrophy (OPTIC ATROPHY, AUTOSOMAL DOMINANT) and Leber hereditary optic atrophy (OPTIC ATROPHY, HEREDITARY, LEBER).
Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)
A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, FOCAL DERMAL HYPOPLASIA, and aplasia cutis congenita.
A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.
An autosomal recessive disorder caused by a deficiency of acid beta-glucosidase (GLUCOSYLCERAMIDASE) leading to intralysosomal accumulation of glycosylceramide mainly in cells of the MONONUCLEAR PHAGOCYTE SYSTEM. The characteristic Gaucher cells, glycosphingolipid-filled HISTIOCYTES, displace normal cells in BONE MARROW and visceral organs causing skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement.
A subcategory of chaperonins found in ARCHAEA and the CYTOSOL of eukaryotic cells. Group II chaperonins form a barrel-shaped macromolecular structure that is distinct from GROUP I CHAPERONINS in that it does not utilize a separate lid like structure to enclose proteins.
Enzymes that hydrolyze O-glucosyl-compounds. (Enzyme Nomenclature, 1992) EC 3.2.1.-.
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.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
A group of inherited diseases that share similar phenotypes but are genetically diverse. Different genetic loci for autosomal recessive, autosomal dominant, and x-linked forms of hereditary spastic paraplegia have been identified. Clinically, patients present with slowly progressive distal limb weakness and lower extremity spasticity. Peripheral sensory neurons may be affected in the later stages of the disease. (J Neurol Neurosurg Psychiatry 1998 Jan;64(1):61-6; Curr Opin Neurol 1997 Aug;10(4):313-8)
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
A congenital anomaly of the hand or foot, marked by the presence of supernumerary digits.
A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
An infant during the first month after birth.
A group of HEREDITARY AUTOINFLAMMATION DISEASES, characterized by recurrent fever, abdominal pain, headache, rash, PLEURISY; and ARTHRITIS. ORCHITIS; benign MENINGITIS; and AMYLOIDOSIS may also occur. Homozygous or compound heterozygous mutations in marenostrin gene result in autosomal recessive transmission; simple heterozygous, autosomal dominant form of the disease.
A heterogeneous group of inherited MYOPATHIES, characterized by wasting and weakness of the SKELETAL MUSCLE. They are categorized by the sites of MUSCLE WEAKNESS; AGE OF ONSET; and INHERITANCE PATTERNS.
A group of inherited metabolic disorders involving the enzymes responsible for the synthesis and degradation of glycogen. In some patients, prominent liver involvement is presented. In others, more generalized storage of glycogen occurs, sometimes with prominent cardiac involvement.
Clinically atypical nevi (usually exceeding 5 mm in diameter and having variable pigmentation and ill defined borders) with an increased risk for development of non-familial cutaneous malignant melanoma. Biopsies show melanocytic dysplasia. Nevi are clinically and histologically identical to the precursor lesions for melanoma in the B-K mole syndrome. (Stedman, 25th ed)
Transmission of gene defects or chromosomal aberrations/abnormalities which are expressed in extreme variation in the structure or function of the eye. These may be evident at birth, but may be manifested later with progression of the disorder.
Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.
Species- or subspecies-specific DNA (including COMPLEMENTARY DNA; conserved genes, whole chromosomes, or whole genomes) used in hybridization studies in order to identify microorganisms, to measure DNA-DNA homologies, to group subspecies, etc. The DNA probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the DNA probe include the radioisotope labels 32P and 125I and the chemical label biotin. The use of DNA probes provides a specific, sensitive, rapid, and inexpensive replacement for cell culture techniques for diagnosing infections.
An autosomal recessive familial disorder that usually presents in childhood with POLYNEUROPATHY; SENSORINEURAL HEARING LOSS; ICHTHYOSIS; ATAXIA; RETINITIS PIGMENTOSA; and CARDIOMYOPATHIES. (From Joynt, Clinical Neurology, 1991, Ch37, p58-9; Rev Med Interne 1996;17(5):391-8) This condition can be caused by mutation in the genes encoding peroxisomal phytanoyl-CoA hydroxylase or proteins associated peroxisomal membrane, leading to impaired catabolism of PHYTANIC ACID in PEROXISOMES.
A country in western Europe bordered by the Atlantic Ocean, the English Channel, the Mediterranean Sea, and the countries of Belgium, Germany, Italy, Spain, Switzerland, the principalities of Andorra and Monaco, and by the duchy of Luxembourg. Its capital is Paris.
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.
Autosomal recessive hereditary disorders characterized by congenital SENSORINEURAL HEARING LOSS and RETINITIS PIGMENTOSA. Genetically and symptomatically heterogeneous, clinical classes include type I, type II, and type III. Their severity, age of onset of retinitis pigmentosa and the degree of vestibular dysfunction are variable.
Mapping of the KARYOTYPE of a cell.
Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.
A glycosidase that hydrolyzes a glucosylceramide to yield free ceramide plus glucose. Deficiency of this enzyme leads to abnormally high concentrations of glucosylceramide in the brain in GAUCHER DISEASE. EC 3.2.1.45.
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.
Computer-based representation of physical systems and phenomena such as chemical processes.
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.
An amino acid-specifying codon that has been converted to a stop codon (CODON, TERMINATOR) by mutation. Its occurance is abnormal causing premature termination of protein translation and results in production of truncated and non-functional proteins. A nonsense mutation is one that converts an amino acid-specific codon to a stop codon.
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.
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.
Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
DNA present in neoplastic tissue.
Procedures for identifying types and strains of bacteria. The most frequently employed typing systems are BACTERIOPHAGE TYPING and SEROTYPING as well as bacteriocin typing and biotyping.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION.
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.
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
The application of molecular biology to the answering of epidemiological questions. The examination of patterns of changes in DNA to implicate particular carcinogens and the use of molecular markers to predict which individuals are at highest risk for a disease are common examples.
Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia.
The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.
Individuals whose ancestral origins are in the continent of Europe.
Parliamentary democracy located between France on the northeast and Portugual on the west and bordered by the Atlantic Ocean and the Mediterranean Sea.
DNA sequences encoding RIBOSOMAL RNA and the segments of DNA separating the individual ribosomal RNA genes, referred to as RIBOSOMAL SPACER DNA.
A general term for the complete or partial loss of the ability to hear from one or both ears.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Gel electrophoresis in which the direction of the electric field is changed periodically. This technique is similar to other electrophoretic methods normally used to separate double-stranded DNA molecules ranging in size up to tens of thousands of base-pairs. However, by alternating the electric field direction one is able to separate DNA molecules up to several million base-pairs in length.
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.
Process of determining and distinguishing species of bacteria or viruses based on antigens they share.
Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.
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.
Actual loss of portion of a chromosome.
A method for comparing two sets of chromosomal DNA by analyzing differences in the copy number and location of specific sequences. It is used to look for large sequence changes such as deletions, duplications, amplifications, or translocations.
Autosomal dominant neurocutaneous syndrome classically characterized by MENTAL RETARDATION; EPILEPSY; and skin lesions (e.g., adenoma sebaceum and hypomelanotic macules). There is, however, considerable heterogeneity in the neurologic manifestations. It is also associated with cortical tuber and HAMARTOMAS formation throughout the body, especially the heart, kidneys, and eyes. Mutations in two loci TSC1 and TSC2 that encode hamartin and tuberin, respectively, are associated with the disease.
Persons or animals having at least one parent in common. (American College Dictionary, 3d ed)
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.
A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)
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.
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.
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.
A group of homologous proteins which form the intermembrane channels of GAP JUNCTIONS. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions.
A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
A family composed of spouses and their children.
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.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
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.
A discipline concerned with studying biological phenomena in terms of the chemical and physical interactions of molecules.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.

Alternative splicing of transcripts encoding the alpha- and beta-subunits of mouse glucosidase II in T lymphocytes. (1/1332)

Glucosidase II is a processing enzyme of the endoplasmic reticulum that functions to hydrolyze two glucose residues in immature N -linked oligosaccharides attached to newly synthesized polypeptides. We previously reported the cDNA cloning of the alpha- and beta-subunits of mouse glucosidase II from T cells following copurification of these proteins with the highly glycosylated transmembrane protein-tyrosine phosphatase CD45. Subsequent examination of additional cDNA clones, coupled with partial genomic DNA sequencing, has revealed that both subunits are encoded by gene products that undergo alternative splicing in T lymphocytes. The catalytic alpha-subunit possesses two variably expressed segments, box Alpha1, consisting of 22 amino acids located proximal to the amino-terminus, and box Alpha2, composed of 9 amino acids situated between the amino-terminus and the putative catalytic site in the central region of the molecule. Box Beta1, a variably expressed 7 amino acid segment in the beta-subunit of glucosidase II, is located immediately downstream of an acidic stretch near the carboxyl-terminus. Screening of reverse transcribed RNA by polymerase chain reaction confirms the variable inclusion of each of these segments in transcripts obtained from a panel of T-lymphocyte cell lines. Thus, distinct isoforms of glucosidase II exist that may perform specialized functions.  (+info)

Sequence heterogeneity within three different regions of the hepatitis G virus genome. (2/1332)

Two sets of primers derived from the 5'-terminal region and the NS5 region of the hepatitis G virus (HGV) genome were used to amplify PCR fragments from serum specimens obtained from different parts of the world. All PCR fragments from the 5'-terminal region (5'-PCR, n = 56) and from the NS5 region (NS5-PCR, n = 85) were sequenced and compared to corresponding published HGV sequences. The range of nucleotide sequence similarity varied from 74 and 78% to 100% for 5'-PCR and NS5-PCR fragments, respectively. Additionally, five overlapping PCR fragments comprising an approximately 2.0-kb structural region of the HGV genome were sequenced from each of five sera obtained from three United States residents. These sequences were compared to 20 published sequences comprising the same region of the HGV genome. Nucleotide and deduced amino acid sequences obtained from different individuals were homologous from 82.9 to 93. 6% and from 90.4 to 99.0%, respectively. Sequences obtained from follow-up specimens were almost identical. Comparative analysis of deduced amino acid sequences of the HGV structural proteins and hepatitis C virus (HCV) structural proteins combined with an analysis of predicted secondary structures and hydrophobic profiles allowed prediction of processing sites within the HGV structural proteins. A phylogenetic sequence analysis performed on the 2.0-kb structural region supports the existence of three previously identified HGV genetic groups. However, phylogenetic analysis performed on only small DNA fragments yielded inconsistent genetic grouping and failed to confirm the existence of genetic groups. Thus, in contrast to HCV where almost any region can be used for genotyping, only large or carefully selected genome fragments can be used to identify consistent HGV genetic groups.  (+info)

Analysis of chromosome 1q42.2-43 in 152 families with high risk of prostate cancer. (3/1332)

One hundred fifty-two families with prostate cancer were analyzed for linkage to markers spanning a 20-cM region of 1q42.2-43, the location of a putative prostate cancer-susceptibility locus (PCAP). No significant evidence for linkage was found, by use of both parametric and nonparametric tests, in our total data set, which included 522 genotyped affected men. Rejection of linkage may reflect locus heterogeneity or the confounding effects of sporadic disease in older-onset cases; therefore, pedigrees were stratified into homogeneous subsets based on mean age at diagnosis of prostate cancer and number of affected men. Analyses of these subsets also detected no significant evidence for linkage, although LOD scores were positive at higher recombination fractions, which is consistent with the presence of a small proportion of families with linkage. The most suggestive evidence of linkage was in families with at least five affected men (nonparametric linkage score of 1.2; P=.1). If heterogeneity is assumed, an estimated 4%-9% of these 152 families may show linkage in this region. We conclude that the putative PCAP locus does not account for a large proportion of these families with prostate cancer, although the linkage of a small subset is compatible with these data.  (+info)

Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-IgA antibodies in disease predisposition. (4/1332)

Immunoglobulin A (IgA) deficiency (IgAD) is characterized by a defect of terminal lymphocyte differentiation, leading to a lack of IgA in serum and mucosal secretions. Familial clustering, variable population prevalence in different ethnic groups, and a predominant inheritance pattern suggest a strong genetic predisposition to IgAD. The genetic susceptibility to IgAD is shared with a less prevalent, but more profound, defect called "common variable immunodeficiency" (CVID). Here we show an increased allele sharing at 6p21 in affected members of 83 multiplex IgAD/CVID pedigrees and demonstrate, using transmission/diseqilibrium tests, family-based associations indicating the presence of a predisposing locus, designated "IGAD1," in the proximal part of the major histocompatibility complex (MHC). The recurrence risk of IgAD was found to depend on the sex of parents transmitting the defect: affected mothers were more likely to produce offspring with IgAD than were affected fathers. Carrier mothers but not carrier fathers transmitted IGAD1 alleles more frequently to the affected offspring than would be expected under random segregation. The differential parent-of-origin penetrance is proposed to reflect a maternal effect mediated by the production of anti-IgA antibodies tentatively linked to IGAD1. This is supported by higher frequency of anti-IgA-positive females transmitting the disorder to children, in comparison with female IgAD nontransmitters, and by linkage data in the former group. Such pathogenic mechanisms may be shared by other MHC-linked complex traits associated with the production of specific autoantibodies, parental effects, and a particular MHC haplotype.  (+info)

ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families. (5/1332)

Combined factors V and VIII deficiency is an autosomal recessive bleeding disorder associated with plasma levels of coagulation factors V and VIII approximately 5% to 30% of normal. The disease gene was recently identified as the endoplasmic reticulum-Golgi intermediate compartment protein ERGIC-53 by positional cloning, with the detection of two founder mutations in 10 Jewish families. To identify mutations in additional families, the structure of the ERGIC-53 gene was determined by genomic polymerase chain reaction (PCR) and sequence analysis of bacterial artificial chromosome clones containing the ERGIC-53 gene. Nineteen additional families were analyzed by direct sequence analysis of the entire coding region and the intron/exon junctions. Seven novel mutations were identified in 10 families, with one additional family found to harbor one of the two previously described mutations. All of the identified mutations would be predicted to result in complete absence of functional ERGIC-53 protein. In 8 of 19 families, no mutation was identified. Genotyping data indicate that at least two of these families are not linked to the ERGIC-53 locus. Taken together, these results suggest that a significant subset of combined factors V and VIII deficiency is due to mutation in one or more additional genes.  (+info)

Thrombophilia as a multigenic disease. (6/1332)

BACKGROUND AND OBJECTIVE: Venous thrombosis is a common disease annually affecting 1 in 1000 individuals. The multifactorial nature of the disease is illustrated by the frequent identification of one or more predisposing genetic and/or environmental risk factors in thrombosis patients. Most of the genetic defects known today affect the function of the natural anticoagulant pathways and in particular the protein C system. This presentation focuses on the importance of the genetic factors in the pathogenesis of inherited thrombophilia with particular emphasis on those defects which affect the protein C system. INFORMATION SOURCES: Published results in articles covered by the Medline database have been integrated with our original studies in the field of thrombophilia. STATE OF THE ART AND PERSPECTIVES: The risk of venous thrombosis is increased when the hemostatic balance between pro- and anti-coagulant forces is shifted in favor of coagulation. When this is caused by an inherited defect, the resulting hypercoagulable state is a lifelong risk factor for thrombosis. Resistance to activated protein C (APC resistance) is the most common inherited hypercoagulable state found to be associated with venous thrombosis. It is caused by a single point mutation in the factor V (FV) gene, which predicts the substitution of Arg506 with a Gln. Arg506 is one of three APC-cleavage sites and the mutation results in the loss of this APC-cleavage site. The mutation is only found in Caucasians but the prevalence of the mutant FV allele (FV:Q506) varies between countries. It is found to be highly prevalent (up to 15%) in Scandinavian populations, in areas with high incidence of thrombosis. FV:Q506 is associated with a 5-10-fold increased risk of thrombosis and is found in 20-60% of Caucasian patients with thrombosis. The second most common inherited risk factor for thrombosis is a point mutation (G20210A) in the 3' untranslated region of the prothrombin gene. This mutation is present in approximately 2% of healthy individuals and in 6-7% of thrombosis patients, suggesting it to be a mild risk factor of thrombosis. Other less common genetic risk factors for thrombosis are the deficiencies of natural anticoagulant proteins such as antithrombin, protein C or protein S. Such defects are present in less than 1% of healthy individuals and together they account for 5-10% of genetic defects found in patients with venous thrombosis. Owing to the high prevalence of inherited APC resistance (FV:Q506) and of the G20210A mutation in the prothrombin gene, combinations of genetic defects are relatively common in the general population. As each genetic defect is an independent risk factor for thrombosis, individuals with multiple defects have a highly increased risk of thrombosis. As a consequence, multiple defects are often found in patients with thrombosis.  (+info)

Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes. (7/1332)

Sanfilippo B syndrome (mucopolysaccharidosis IIIB, MPS IIIB) is caused by a deficiency of alpha-N-acetylglucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulphate. Accumulation of the substrate in lysosomes leads to degeneration of the central nervous system with progressive dementia often combined with hyperactivity and aggressive behaviour. Age of onset and rate of progression vary considerably, whilst diagnosis is often delayed due to the absence of the pronounced skeletal changes observed in other mucopolysaccharidoses. Cloning of the gene and cDNA encoding alpha-N-acetylglucosaminidase enabled a study of the molecular basis of this syndrome. We were able to identify 31 mutations, 25 of them novel, and two polymorphisms in the 40 patients mostly of Australasian and Dutch origin included in this study. The observed allellic heterogeneity reflects the wide spectrum of clinical phenotypes reported for MPS IIIB patients. The majority of changes are missense mutations; also four nonsense and nine frameshift mutations caused by insertions or deletions were identified. Only five mutations were found in more than one patient and the observed frequencies are well below those observed for the common mutations in MPS IIIA. R643C and R297X each account for around 20% of MPS IIIB alleles in the Dutch patient group, whilst R297X, P521L, R565W and R626X each have a frequency of about 6% in Australasian patients. R643C seems to be a Dutch MPS IIIB allele and clearly confers the attenuated phenotype. One region of the gene shows a higher concentration of mutations, probably reflecting the instability of this area which contains a direct repeat. Several arginine residues seem to be 'hot-spots' for mutations, being affected by two or three individual base pair exchanges.  (+info)

Heterogeneity of T-cell receptor usage in experimental autoimmune neuritis in the Lewis rat. (8/1332)

In experimental autoimmune neuritis (EAN), T-cell receptor (TCR) variable (V)-region gene usage by neuritogenic T cells has been reported to be clonally restricted at the RNA level. This study was designed to verify TCR usage by neuritogenic T cells at the protein level. We generated two monoclonal antibodies (mAbs) 7H4 and 8G8 specific for a Vbeta4/Valpha11 associated idiotype expressed by the majority of neuritogenic cells of P2-specific T-cell lines. The remaining neuritogenic P2-specific T cells either exhibited a dominant usage of the TCR Vbeta13 chain recognized by the recently generated mAbs 17D5 and 18B1 or showed diverse Vbeta usage. Treatment of adoptive-transfer (AT)-EAN or of EAN actively induced with the neuritogenic P2 peptide by mAbs 7H4 and 8G8 led to a partial, but significant, reduction of clinical disease. Treatment with Vbeta13-specific mAb 17D5 had no clear effect on active EAN. Our data show that at least three different TCR are used by P2-specific pathogenic T cells in EAN, an animal model for human inflammatory neuropathies.  (+info)

TY - JOUR. T1 - Genetic heterogeneity in HER2 testing in breast cancer panel summary and guidelines. AU - Vance, Gail H.. AU - Barry, Todd S.. AU - Bloom, Kenneth J.. AU - Fitzgibbons, Patrick L.. AU - Hicks, David G.. AU - Jenkins, Robert B.. AU - Persons, Diane L.. AU - Tubbs, Raymond R.. AU - Hammond, M. Elizabeth H.. PY - 2009/4/1. Y1 - 2009/4/1. N2 - • Context.-Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%. The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist. Objectives.-To define HER2 genetic heterogeneity and to provide practice guidelines for examining and reporting breast tumors with genetic heterogeneity for improvement of HER2 testing in breast cancer. Design.-We convened an expert panel to discuss HER2 gene ...
Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tu …
Supplementary Fig. S5 - Supplementary Fig. S5. Validation of redundant APC mutations. A, For one case (CRC2), two redundant APC mutations are validated by Sanger sequencing. One nonsense mutation (C,T; left) and one frameshift indel (AG,A; right) are shown for seven regional biopsies for the given case. For one primary case (CRC2-P1), the nonsense mutation is not observed, consistent with the metastasis-clonal presentation of this mutation. B, The copy number changes of the entire chromosome 5 are shown for seven regional biopsies. Entire loss of chromosome 5 is observed for CRC-P1. APC locus is incidated with a red dotted line ...
PCAP(3) Library Functions Manual PCAP(3) NAME pcap - Packet Capture library SYNOPSIS #include ,pcap.h, char errbuf[PCAP_ERRBUF_SIZE]; pcap_t *pcap_open_live(const char *device, int snaplen, int promisc, int to_ms, char *errbuf) pcap_t *pcap_open_dead(int linktype, int snaplen) pcap_t *pcap_open_offline(const char *fname, char *errbuf) pcap_t *pcap_fopen_offline(FILE *fp, char *errbuf) pcap_dumper_t *pcap_dump_open(pcap_t *p, const char *fname) pcap_dumper_t *pcap_dump_fopen(pcap_t *p, FILE *fp) int pcap_setnonblock(pcap_t *p, int nonblock, char *errbuf); int pcap_getnonblock(pcap_t *p, char *errbuf); int pcap_findalldevs(pcap_if_t **alldevsp, char *errbuf) void pcap_freealldevs(pcap_if_t *alldevs) char *pcap_lookupdev(char *errbuf) int pcap_lookupnet(const char *device, bpf_u_int32 *netp, bpf_u_int32 *maskp, char *errbuf) typedef void (*pcap_handler)(u_char *user, const struct pcap_pkthdr *h, const u_char *bytes); int pcap_dispatch(pcap_t *p, int cnt, pcap_handler callback, u_char *user) int ...
article{c94ded92-04be-4181-80c1-f13a7f07a88b, abstract = {,p,Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fishers exact test) was found in CSDhigh melanomas. Sequencing of multiple ...
Despite dramatic advances and widespread clinical adoption of genetic testing for the identification of interpatient genetic variation, treatment with targeted drugs and temporary effectiveness, these agents only prolong survival for a few months [1]. Recent data suggest that shifting from single biopsy-based testing to comprehensive intratumor diversity using next-generation sequencing (NGS) technologies could reduce tumor resistance to modern therapy. Could intratumor heterogeneity be used as a biomarker to predict primary tumor responsiveness and improve initial systemic treatment ...
Cancer arises from accumulation of somatic mutations and accompanying evolutionary selection for growth advantage. During the evolutionary process, an ancestor clone branches into multiple clones, yielding intratumor heterogeneity. However, principles underlying intratumor heterogeneity have been poorly understood. Here, to explore the principles, we built a cellular automaton model, termed the BEP model, which can reproduce the branching cancer evolution in silico. We then extensively searched for conditions leading to high intratumor heterogeneity by performing simulations with various parameter settings on a supercomputer. Our result suggests that multiple driver genes of moderate strength can shape subclonal structures by positive natural selection. Moreover, we found that high mutation rate and a stem cell hierarchy can contribute to extremely high intratumor heterogeneity, which is characterized by fractal patterns, through neutral evolution. Collectively, This study identified the ...
Background & Aims Intratumor heterogeneity is a common feature of colorectal cancers (CRC). and enough for inducing EMT, invasion, and migration in epithelial-like CRC cells. In principal CRCs, increased appearance was connected with mutation and microRNA-192/215 down-regulation. Significantly, increased appearance in CRCs correlated with improved tumor development and poor individual survival. Conclusions together Taken, our results present that CRC cells promote tumor development via secreting NID1, which induces EMT in neighboring tumor cells. Significantly, the disturbance of p53 with this paracrine signaling between tumor cells?might?donate to tumor suppression critically. (had been up-regulated on the amount of messenger RNA (mRNA) appearance in DLD1, HCT15, HCT116, and LoVo cells following the addition of CM from mesenchymal-like CRC cell lines (Body?1and 1and and in DLD1, HCT15, HCT116, LoVo, HT29, and Caco2 cells cultured for 96 hours in CM extracted from SW480 or SW620 cells. Mean ...
Although cancer stemness, antitumor immunity, and intratumoral heterogeneity have all emerged as important features of cancer in recent years, their covariation across cancers has not been systematically investigated. Here we report that stemness is associated with suppressed immune response, higher intratumoral heterogeneity, and dramatically worse outcome for the majority of cancers. Although correlative analyses such as ours do not reveal causality, we propose that the stemness phenotype found in cancer cells, similar to that in normal stem cells, involves the expression of immunosuppressive factors that engender the formation of immune-privileged microenvironments in which tumor clone diversification can occur. The resulting heterogeneity may provide a substrate for the selection of treatment-resistant clones, resulting in inferior clinical outcomes. Thus, our findings implicate stemness as a shared therapeutic target to achieve the dual objectives of constraining tumor evolution and ...
RPMI-8402 is a genetically heterogenous T-ALL cell line (9). Using DNA sequencing, the present study identified a heterozygous Arg-Cys mutation at codon 273 of the TP53 gene in RPMI-8402 cells, with varying proportions of the templates (50-75% of WT allele), depending on cell confluence. Additionally, FISH analysis detected a variable number of copies of the chromosome 17 in RPMI-8402 cells, while ICC analysis revealed two different cell populations, exhibiting high and low protein expression levels of TP53, respectively, which suggests genetic heterogeneity of the RPMI-8402 cell line. Cell sorting analysis identified heterogeneity of PTEN and TP53 mutations, but an homozygous mutation in the FBXW7 gene was detected in both cell populations. Furthermore, massive parallel sequencing confirmed the genetic heterogeneity of RPMI-8402 cells, and excluded the possibility of cross-contamination with another cell line. The comparison between the results obtained with Ion Torrent™ and Sanger sequencing ...
Our study highlights some of the myriad biologic differences between cell lines and primary tumor specimens as well as the genetic differences between tumors from different patients. A study utilizing data from TCGA categorized GBM tumors into four main subtypes based on molecular profiling (13); however, other studies asserted that there could be distinct variability within a single tumor and even the presence of multiple subtypes of single GBM tumor cells (18, 45, 46). Intratumor heterogeneity may arise from the divergent phenotypic and genetic profiles of BCSCs (3, 11, 47, 48); furthermore, multiple stem cell clones can maintain distinct populations within the same tumor (intratumor heterogeneity; ref. 49) that interact with each other, providing support and complex signaling (46). These nuances make an already challenging cancer to manage even more of a complex signaling maze to target. Therefore, the predicted heterogeneity of chemoresistance requires better in vitro models before investing ...
Charge heterogeneity of monoclonal antibodies is an important critical quality attribute that requires close monitoring due to its potential impact on antibody efficacy and immunogenicity. Since the heterogeneity is mostly caused by post translational modifications such as C-terminal lysine clipping, deamidation, glycation, sialic acid or adduct formation, these modifications can pose significant challenges to the analytical scientists.. In a recently published article by Jaag et al., scientists from the Institute of Pharmaceutical Sciences at University at Tübingen, Germany, present a new approach to charge variant analysis at the intact and sub-unit level by 2D-LC separation. In this workflow, the first-dimension separation is based on strong-cation chromatography (SCX) and the second-dimension separation is based on desalting reversed phase liquid chromatography (RP-HPLC) which enables combination with the mass analysis by mass spectrometric (MS) detection.. The analysis at the subunit level ...
Lalonde E., Ishkanian AS., Sykes J., Fraser M., Ross-Adams H., Erho N., Dunning M., Lamb AD., Moon NC., Zafarana G., Warren AY., Meng A., Thoms J., Grzadkowski MR., Berlin A., Halim S., Have CL., Ramnarine VR., Yao CQ., Malloff CA., Lam LL., Xie H., Harding NJ., Mak DYF., Chu KC., Chong LC., Sendorek DH., Png C., Ahmed O., Collins CC., Squire JA., Jurisica I., Cooper C., Eeles R., Pintilie M., Dal Pra A., Davicioni E., Lam WL., Milosevic M., Neal DE., van der Kwast T., Boutros PC., Bristow RG ...
Purpose: To identify an optimal drug combination for addressing intratumor heterogeneity by measuring single drug responses at the level of single cells.. Background: Drug combination strategies have been derived from drug-drug and drug-target interaction inferences made based on genomic network analysis, such as synthetic lethality network analysis and protein network analysis. A key limitation with these approaches is that they do not account for intratumor heterogeneity. A next generation high throughput single cell technology such as Cytometry Time-of-Flight (CyTOF) has the potential to circumvent this limitation by providing the key information for optimally targeting intratumor heterogeneity within the context of personalized medicine.. Methods: We propose a systems level modeling framework for analyzing heterogeneous drug response data across a population of single cells. Our approach, called Mixture Nested Effects Models (MNEM), identifies multi-target drug combinations from single drug ...
Previous studies in pig models showed that the effective prescribed dose for brachytherapy using a gamma source was 3.5 to 14 Gy at 2 mm (9)or 15 to 20 Gy at 1.5 mm (10-12)from the center of the lumen. Ideally, treatment protocols should be designed to deliver a uniform dose to the target; however, the source is rarely centered within the lumen, and the lumen and stent are rarely centered within the artery. This precludes centering the source within the artery and delivering a uniform dose to the adventitia.. Human ISR treatment protocols using gamma irradiation have selected either a fixed prescription (e.g., 15 Gy at 2 mm from the center of the source [3]) or a calculated and variable dose prescription (minimum of 8 Gy as long as the maximum dose is limited to 30 Gy [2,13]). However, in these ISR protocols, there have been little attempts to calculate the actual delivered dose and the affect of the delivered dose on the biologic process-neointimal regrowth. As shown in Figures 1 and 2, the ...
Among the 629 patients, 30 (4.8%) had ALK fusions, 364 (57.9%) had EGFR mutations, and two had ALK fusions that coexisted with EGFR mutations. Intratumoral heterogeneity of ALK fusions were identified in nine patients by reverse-transcriptase polymerase chain reaction. In the two patients with an ALK/EGFR coaltered status, genetic intratumoral heterogeneity was observed both between different growth patterns and within the same growth pattern. The relative abundance of ALK and EGFR alterations was different in the same captured area. ALK fusions were positively associated with a micropapillary pattern (P = .002) and were negatively associated with a lepidic pattern (P = .008) in an expanded statistical analysis of 900 individual adenocarcinoma components, although they appeared to be more common in acinar-predominant LADCs in the analysis of 629 patients.. Conclusion ...
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Heterogeneity is universally observed in all natural systems and across multiple scales. Understanding population heterogeneity is an intriguing and attractive topic of research in different...
In NSCLC and other cancers, molecular testing is becoming an integral part of patient management. However, tumor biopsies from NSCLC patients can present challenges for molecular analyses due to inadequate or insufficient sample material, tumor heterogeneity, or the presence of lesions that are inaccessible to needle biopsy in patients at risk for complications due to comorbidities. These challenges are accentuated in a later line setting because rebiopsy may not be feasible and tumor heterogeneity may be greater in patients with acquired resistance to targeted therapies. Previous studies have shown that the detection of mutations in blood, specifically in circulating tumor DNA (ctDNA) from plasma, can potentially overcome these limitations (1, 14, 16-18). Using a series of matched blood and plasma samples drawn from two studies, we have extended these observations to a large cohort of NSCLC patients with a focus on the acquired resistance mutation T790M where existing data from published ...
Bioconductor version: Development (3.13) AneuFinder implements functions for copy-number detection, breakpoint detection, and karyotype and heterogeneity analysis in single-cell whole genome sequencing and strand-seq data.. Author: Aaron Taudt, Bjorn Bakker, David Porubsky Maintainer: Aaron Taudt ,aaron.taudt at gmail.com, ...
Wireline formation microelectrical imaging has been used for many decades to characterize reservoirs. The geological interpretation of image data is mainly used for structural analysis, fracture characterization, porosity analysis, heterogeneity analysis, rock typing, and facies classification. In addition, formation microelectrical images are commonly needed for complex reservoirs to help with the selection of wireline formation tester straddle packer locations. The quality of the data acquired using conventional formation microelectrical imaging tools may be degraded in highly resistive formations even with conductive mud because of the high noise-to-signal ratio, which can lead to fuzzy images with very few geological features visible. Phase shift, which is common in resistive formations, can result in reversed images, reversed contrast, and pad/flap mismatch, which can render the data unusable. A new tool for microelectrical imaging presents a solution to this problem by obtaining high-definition,
Frayling, T. M. , Lindgren, C. M. , Chevre, J. C. , Menzel, S. , Wishart, M. , Benmezroua, Y. , Brown, A. , Evans, J. C. , Rao, P. S. , Dina, C. , Lecoeur, C. , Kanninen, T. , Almgren, P. , Bulman, M. P. , Wang, Y. , Mills, James L., Wright-Pascoe, Rosemarie A., Mahtani, M. M. , Prisco, F. , Costa, A. , Cognet, I. , Hansen, T. , Pedersen, O. , Ellard, S. , Tuomi, T. , Groop, L. C. , Froguel, P. , Hattersley, A. T. , Vaxillaire, M. . Genome-Wide Scan in Families With Maturity-Onset Diabetes of the Young: Evidence for Further Genetic Heterogeneity ...
Many liver cancer tumors contain a highly diverse set of cells, a phenomenon known as intra-tumor heterogeneity that can significantly affect the rate at which the cancer grows, Mount Sinai researchers report. The immune systems contribution to this heterogeneity can have major clinical implications.
XS(XS_Net__Pcap_file); /* prototype to pass -Wmissing-prototypes */ XS(XS_Net__Pcap_file) { dXSARGS; if (items != 1) Perl_croak(aTHX_ Usage: Net::Pcap::file(p)); { pcap_t * p; FILE * RETVAL; if (sv_derived_from(ST(0), pcap_tPtr)) { IV tmp = SvIV((SV*)SvRV(ST(0))); p = (pcap_t *) tmp; } else croak(p is not of type pcap_tPtr); RETVAL = pcap_file(p); ST(0) = sv_newmortal(); { GV *gv = newGVgen(Net::Pcap); if ( do_open(gv, ,&, 2, FALSE, 0, 0, RETVAL) ) sv_setsv(ST(0), sv_bless(newRV((SV*)gv), gv_stashpv(Net::Pcap +,1))); else ST(0) = &PL_sv_undef; } } XSRETURN(1 ...
The Journal of Pathology is now soliciting submissions of primary research based on massively parallel sequencing taking advantage of novel insights into the genetic basis of human diseases, including the identification of new genotype-phenotype associations and novel driver mutations, characterization of patterns of genetic instability, and on the topic of intra-tumour genetic heterogeneity ...
You can search for any reference by title, author, date, editor, journal and publisher. Searching is case insensitive, and allows for only partial terms (e.g. seq with pickup both RNA-Seq and sequencing) matching. You can also use advanced queries that are detailed here. ...
The purpose of this work is two-fold: (1) to develop a novel mathematical and computational framework that incorporates the major sources of cell population heterogeneity and (2) to use this framework to demonstrate the effect of stochasticity on cell population heterogeneity in an artificial lac operon genetic network. During the past decades, several approaches have been used to model heterogeneity in bacterial cell populations, each approach focusing on different source(s) of heterogeneity. However, a holistic approach that integrates all the major sources into a generic framework is still lacking. In this work we present a mathematical and computational framework that describes single cells or cell populations and takes into account stochasticity in reaction, division and DNA duplication, all of which constitute sources of cell population heterogeneity. We subsequently use this framework to demonstrate how stochasticity generates complex behavior and phenotypic heterogeneity in the case of ...
Although the presence of genetic heterogeneity within the tumors of individual patients is established, it is unclear whether greater heterogeneity predicts a worse outcome. A quantitative measure of genetic heterogeneity based on next-generation sequencing (NGS) data, mutant-allele tumor heterogeneity (MATH), was previously developed and applied to a data set on head and neck squamous cell carcinoma (HNSCC). Whether this measure correlates with clinical outcome was not previously assessed. ...
Allelic heterogeneity is the phenomenon in which different mutations at the same locus cause the same phenotype. These allelic variations can arise as a result of natural selection processes, as a result of exogenous mutagens, genetic drift, or genetic migration. Many of these mutations take the form of single nucleotide polymorphisms in which a single nucleotide base is altered compared to a consensus sequence. They can also exist as copy number variants (CNV) in which the copies of a gene or DNA sequence is different from the population. Mutated alleles expressing allelic heterogeneity can be classified as adaptive or disadaptive. These mutations can occur in the germ line cells, somatic cells, or in the mitochondrial. Mutations in germ line cells can be inherited as well as mitochondrial allelic mutations. The mitochondrial allelic mutations are inherited maternally. Typically in the human genome a small amount of allele variants account for ~75% of the mutations found at a particular locus ...
BACKGROUND Adenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed.METHODS An integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.RESULTS Compared with primary tumors, R/M tumors were enriched for alterations in key Notch (NOTCH1, 26.3% vs. 8.5%; NOTCH2, 4.6% vs. 2.3%; NOTCH3, 5.7% vs. 2.3%; NOTCH4, 3.6% vs. 0.6%) and chromatin-remodeling (KDM6A, 15.2% vs. 3.4%; KMT2C/MLL3, 14.3% vs. 4.0%; ARID1B, 14.1% vs. 4.0%) genes. TERT promoter mutations (13.1% of R/M cases) were mutually exclusive with both ...
BACKGROUND Adenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed.METHODS An integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.RESULTS Compared with primary tumors, R/M tumors were enriched for alterations in key Notch (NOTCH1, 26.3% vs. 8.5%; NOTCH2, 4.6% vs. 2.3%; NOTCH3, 5.7% vs. 2.3%; NOTCH4, 3.6% vs. 0.6%) and chromatin-remodeling (KDM6A, 15.2% vs. 3.4%; KMT2C/MLL3, 14.3% vs. 4.0%; ARID1B, 14.1% vs. 4.0%) genes. TERT promoter mutations (13.1% of R/M cases) were mutually exclusive with both ...
BACKGROUND Adenoid cystic carcinoma (ACC) is a rare malignancy arising in salivary glands and other sites, characterized by high rates of relapse and distant spread. Recurrent/metastatic (R/M) ACCs are generally incurable, due to a lack of active systemic therapies. To improve outcomes, deeper understanding of genetic alterations and vulnerabilities in R/M tumors is needed.METHODS An integrated genomic analysis of 1,045 ACCs (177 primary, 868 R/M) was performed to identify alterations associated with advanced and metastatic tumors. Intratumoral genetic heterogeneity, germline mutations, and therapeutic actionability were assessed.RESULTS Compared with primary tumors, R/M tumors were enriched for alterations in key Notch (NOTCH1, 26.3% vs. 8.5%; NOTCH2, 4.6% vs. 2.3%; NOTCH3, 5.7% vs. 2.3%; NOTCH4, 3.6% vs. 0.6%) and chromatin-remodeling (KDM6A, 15.2% vs. 3.4%; KMT2C/MLL3, 14.3% vs. 4.0%; ARID1B, 14.1% vs. 4.0%) genes. TERT promoter mutations (13.1% of R/M cases) were mutually exclusive with both ...
Genetic heterogeneity in autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheats (CMT4B) ...
This latest research article, A Reassessment of Genetic Diversity in Icelanders: Strong Evidence from Multiple Loci for Relative Homogeneity Caused by Genetic Drift by A. Helgason, G. Nicholson, K. Stefánsson and P. Donnelly, both greatly expands sample sizes from individual populations and the number of genetic loci analysed, and uses population genetics simulations to demonstrate that genetic drift, not admixture (as claimed by E. Árnason), has been the overriding factor influencing patterns of genetic variation in Iceland. Moreover, these simulations also reveal that the summary statistics (gene diversity and mean pairwise mutational differences) used by E. Árnason, to argue for the relative genetic heterogeneity of Icelanders in his analysis of mitochondrial DNA (mtDNA) sequences, are poor comparative measures of genetic diversity in closely related populations such as those of Iceland and other European countries ...
Purpose: : Early onset retinal dystrophy (EORD), in which patients present with reduced retinal function before the age of 5 years, shows high genetic heterogeneity; 9 identified genes being responsible for approximately 50% of cases. This complexity hinders efficient molecular diagnosis. One approach is to use DNA arrays to interrogate many distinct variants in one hybridisation reaction. Methods: : 100 unrelated patients with EORD were screened using an array containing 344 published sequence variants in eight genes - AIPL1, GUCY2D, CRB1, CRX, RPGRIP1, RPE65, MERTK and LRAT (AsperBio©). A detailed clinical examination of all probands was performed. DNA was PCR-amplified and hybridised to the array prior to an arrayed-primer-extension-reaction (APEX©). To test the accuracy of the technique, all probands underwent bidirectional sequencing of the whole coding region of the RPE65 gene. Results: : Of the possible 68,900 interrogations on the 100 samples, 1094 (1.6%) failed on one strand whilst ...
We next compared the mutational spectrum of trunk versus nontrunk mutations to explore the relative contribution of mutational processes over time. Significant differences in mutational spectrum were observed in six tumors, which indicated that specific mutational processes were likely operative at different times during development of these tumors (Fig. 3, B and C). Of interest, two former smokers (cases 317 and 330) and the current smoker (case 324) showed significant differences between trunk and nontrunk mutation spectrum with a shift from smoking-associated C,A transversions in trunk mutations to nonsmoker-associated C,T transitions in nontrunk mutations.. Recent evidence has suggested that APOBEC activity is a major source for C,T and C,G mutations (12, 26). We therefore investigated whether there is evidence of an APOBEC mutational process in this subset of lung adenocarcinomas. On average, 28% of all mutations had a specific substitution pattern (C,T/G at TpCpW sites, where W is A or T), ...
Assume an increased risk based on family history for a non-affected person. Allelic and locus heterogeneity may need to be considered.. Index case in that family had been tested:. If the index case in that family had been tested and a causative mutation had been found in the index patient: close to 100%.. Index case in that family had not been tested:. If the patient is clinically affected (prolonged QTc with or without syncope) he/she has a chance of about 70% carrying a disease-causing mutation. But only in very rare cases there is an indication for performing LQTS genetic testing in a clinically unaffected relative when the index case has not been tested.. This could be imaginable when in an index case theres a strong clinical suspicion of LQTS and theres no DNA available or the index patient refuses genetic testing. Usually theres no indication for genetic testing in a clinically unaffected family member with unclear genetic status of the index patient. ...
Uncertainty often affects molecular biology experiments and data for different reasons. Heterogeneity of gene or protein expression within the same tumor tissue is an example of biological uncertainty which should be taken into account when molecular markers are used in decision making. Tissue Microarray (TMA) experiments allow for large scale profiling of tissue biopsies, investigating protein patterns characterizing specific disease states. TMA studies deal with multiple sampling of the same patient, and therefore with multiple measurements of same protein target, to account for possible biological heterogeneity. The aim of this paper is to provide and validate a classification model taking into consideration the uncertainty associated with measuring replicate samples. We propose an extension of the well-known Naïve Bayes classifier, which accounts for biological heterogeneity in a probabilistic framework, relying on Bayesian hierarchical models. The model, which can be efficiently learned from the
In a recent post, Philip Gerlee highlighted the two biggest contributions of mathematical oncology to cancer research: (1) increasing focus on the progress of cancer as an evolutionary process, and (2) looking at the importance of tumor heterogeneity.. For the first point, the standard historical reference is: Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science, 194(4260): 23-28.. However, for the second point, although I am vaguely familiar with modern work, I dont know of a historical reference. When was tumour heterogeneity first recognized as important to cancer dynamics and treatment? Was this work related to mathematical or other modeling insights? If not, what is the first important mathematical (or computational) modeling work on tumour heterogeneity?. ...
Author(s): Liao, David; Estévez-Salmerón, Luis; Tlsty, Thea D | Abstract: Complex biological systems often display a randomness paralleled in processes studied in fundamental physics. This simple stochasticity emerges owing to the complexity of the system and underlies a fundamental aspect of biology called phenotypic stochasticity. Ongoing stochastic fluctuations in phenotype at the single-unit level can contribute to two emergent population phenotypes. Phenotypic stochasticity not only generates heterogeneity within a cell population, but also allows reversible transitions back and forth between multiple states. This phenotypic interconversion tends to restore a population to a previous composition after that population has been depleted of specific members. We call this tendency homeostatic heterogeneity. These concepts of dynamic heterogeneity can be applied to populations composed of molecules, cells, individuals, etc. Here we discuss the concept that phenotypic stochasticity both underlies the
Markus Wolff, Katrine M. Johannesen, Ulrike B. S. Hedrich, Silvia Masnada, Guido Rubboli, et al.. Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain - A Journal of Neurology , Oxford University Press (OUP), 2017, 140 (5), pp.1316 - 1336. 〈10.1093/brain/awx054〉. 〈hal-01668653〉 ...
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The significance of trait expression at the tissue level during morphogenesis has already been demonstrated for the case of the early morphogenetic process of primary embryonic induction. The...
For a policy-maker promoting the end of a harmful tradition, conformist social influence is a compelling mechanism. If an intervention convinces enough people to abandon the tradition, this can spill over and induce others to follow. A key objective is thus to activate such spillovers and amplify an interventions effects. With female genital cutting as a motivating example, we develop empirically informed analytical and simulation models to examine this idea. Even if conformity pervades decision-making, spillovers can range from irrelevant to indispensable. Our analysis highlights three considerations. First, ordinary forms of individual heterogeneity can severely limit spillovers, and understanding the heterogeneity in a population is essential. Second, although interventions often target samples of the population biased towards ending the harmful tradition, targeting a representative sample is a more robust way to achieve spillovers. Finally, if the harmful tradition contributes to group identity,
Complex liquids in natural environments can have spatially heterogeneous properties that influence, and are transported by, a flow. Although diffusion can be expected to suppress spatial gradients over long timescales, heterogeneity will persist in liquids containing large molecular-weight structures with low mobility. In practical applications, the heterogeneity can often be quantified at best at a statistical level, requiring flow outcomes to be described in terms of distributions. The example we present here illustrates some of the challenges of this task. Regions of strong compression quickly generate large spatial gradients in the transported material, far narrower than the physical boundary layers within the flow, which rapidly inflate computational cost; this cost is magnified by the requirement to simulate multiple realizations of the problem.. The example we consider here, motivated by an application in respiratory physiology, illustrates the benefits (and limitations) of low-order ...
Cancers exhibit extensive mutational heterogeneity, and the resulting long-tail phenomenon complicates the discovery of genes and pathways that are significantly mutated in cancer. We perform a pan-cancer analysis of mutated networks in 3,281 samples from 12 cancer types from The Cancer Genome Atlas …
Renal cell carcinoma has a wide and varied clinical presentation and natural history, and this heterogeneity can be problematic when it comes to providing the individualized outcome predictions that...
Results: While Clone 31 displayed a strong ability to initiate tumor growth in vivo, this property was not universally retained among the subclones. While our study was designed to identify processes and properties that correlated with tumorigenicity, we were unable to distinguish any that clearly correlated with this activity. However it is noteworthy that only subclones with mixed epithelial and mesenchymal morphology formed solid tumors in vivo, which Clone 31 is incapable of doing. Further, subclone expression data is suggestive of epithelial mesenchymal plasticity among tumorigenic subclones and thus warrants further investigation ...
Although less well-recognised than for other infectious diseases, heterogeneity is a defining feature of TB epidemiology. To advance toward TB elimination, this heterogeneity must be better understood and addressed. Drivers of heterogeneity in TB epidemiology act at the level of the infectious host, organism, susceptible host, environment and distal determinants. These effects may be amplified by social mixing patterns, while the variable latent period between infection and disease may mask heterogeneity in transmission. Reliance on notified cases may lead to misidentification of the most affected groups, as case detection is often poorest where prevalence is highest. Assuming average rates apply across diverse groups and ignoring the effects of cohort selection may result in misunderstanding of the epidemic and the anticipated effects of control measures. Given this substantial heterogeneity, interventions targeting high-risk groups based on location, social determinants or comorbidities could ...
Scientists have searched for mutations in more than 100 kidney cancer samples, the largest number of samples from a single tumor type to be sequenced to date. They looked for mutations in 3,544 genes to investigate the complexity within this cancer type, which is typically associated with mutations in a gene called VHL. Despite this prevalent genetic signature, the team revealed substantial genetic heterogeneity, suggesting that a complex machinery contributes to the development of cancer.
Chorbadjiev, L., Kendall, J., Alexander, J., Zhygulin, V., Song, J., Wigler, M., Krasnitz, A. (May 2020) Integrated Computational Pipeline for Single-Cell Genomic Profiling. JCO Clinical Cancer Informatics, 4. pp. 464-471. Baslan, T., Kendall, J., Volyanskyy, K., McNamara, K., Cox, H., DItalia, S., Ambrosio, F., Riggs, M., Rodgers, L., Leotta, A., Song, J., Mao, Y., Wu, J., Shah, R., Gularte-Merida, R., Chadalavada, K., Nanjangud, G., Varadan, V., Gordon, A., Curtis, C., Krasnitz, A., Dimitrova, N., Harris, L., Wigler, M., Hicks, J. (May 2020) Novel Insights Into Breast Cancer Copy Number Genetic Heterogeneity Revealed by Single-Cell Genome Sequencing. Elife, 9. e51480. ISSN 2050-084X Vasudevan, A., Baruah, P.S., Smith, J.C., Wang, Z., Sayles, N. M., Andrews, P., Kendall, J., Leu, J., Chunduri, N.K., Levy, D., Wigler, M., Storchova, Z., Sheltzer, J. M. (February 2020) Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer. Developmental Cell, 4 (52). pp. ...
To further understand the immune response, the researchers tried the experiment again, this time on mice specifically engineered to lack T cells - the immune cells that are known to fight cancer. The results were similar to those in mice with weakened immune systems, says Wolf. When we look at T cells from different tumors, we found much more activity in the homogenous growths, and less in the heterogeneous ones. In fact, the researchers found that in the homogeneous growths, T cells had penetrated to the center of the tumor, while in the heterogeneous ones, they remained on the outside, and there were more T cells of a different type - ones that suppress immune activity.. We showed the difference between two extremes - highly homogeneous and highly heterogeneous, says Bartok, but most cancers fall somewhere in between. To systematically generate tumors with intermediate levels of genetic heterogeneity, we created a phylogenetic tree of the parental heterogeneous line, and mapped out how ...
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Bulk analysis often leads to conclusions that assume averages reflect the dominant biological mechanism operating within an entire population. To fully understand how cellular heterogeneity c
Total activity within heterogeneity shows separation in frequency content and increased phase coherence with the sub-threshold driving oscillation when in reson
Genetic heterogeneity in neoplasms[edit]. There are multiple levels of genetic heterogeneity associated with cancer, including ... Since 1976, researchers have identified clonal expansions[24][25][26][27][28][29] and genetic heterogeneity[30][31][32][33][34] ... System instability is a major contributing factor for genetic heterogeneity.[42] For the majority of cancers, genome ... This theory predicts a unique genetic composition in each neoplasm due to the random process of mutations, genetic ...
Dempster, Everett R. (1955-01-01). "Maintenance of Genetic Heterogeneity". Cold Spring Harbor Symposia on Quantitative Biology ... In order for a bet hedging allele to spread, it must persist in the typical environment through genetic drift long enough for ... The sierra dome spider exhibits this behavior as a form of genetic bet hedging, reducing the risk of producing low quality ... Yasui, Yukio (2001-12-01). "Female multiple mating as a genetic bet-hedging strategy when mate choice criteria are unreliable ...
Genetic heterogeneity of seeds]". Ontogenez. 38 (3): 166-191. ISSN 0475-1450. PMID 17621974. Loughry, W. J.; Prodöhl, Paulo A ... The genetic difference between the offspring and the parents, but the similarity among siblings, are significant distinctions ...
"Genetic heterogeneity in osteogenesis imperfecta". J. Med. Genet. 16 (2): 101-16. doi:10.1136/jmg.16.2.101. PMC 1012733. PMID ... Genetic testing[edit]. In order to determine whether osteogenesis imperfecta is present, genetic sequencing of the COL1A1, ... "Genetic Heterogeneity in Osteogenesis Imperfecta". Otology & Neurotology. 33 (9): 1562-1566. doi:10.1097/MAO.0b013e31826bf19b. ... Osteogenesis imperfecta (OI), also known as brittle bone disease, is a group of genetic disorders that mainly affect the bones. ...
Soil heterogeneity effects on community heterogeneity[edit]. Spatial heterogeneity of resources can influence plant community ... Hence ecological restorations are increasingly factoring genetic processes into management practices. Population genetic ... "Soil heterogeneity effects on tallgrass prairie community heterogeneity: an application of ecological theory to restoration ... "Soil Heterogeneity Effects on Tallgrass Prairie Community Heterogeneity: An Application of Ecological Theory to Restoration ...
Phenotypic heterogeneity but genetic homogeneity". Hepatology. 29 (2): 506-8. doi:10.1002/hep.510290214. PMID 9918928. S2CID ... Harris MJ, Le Couteur DG, Arias IM (2006). "Progressive familial intrahepatic cholestasis: genetic disorders of biliary ...
CE did instigate genetic heterogeneity. Another major population change occurred in the 17th c. CE after Bedouin tribes from ... The aim of the authors was to identify any admixture and continuity in the genetic makeup of the European settlers in the ... In order to establish an approach for the evaluation of a possible genetic and socio-historical context correlated with OA, ... Nonetheless, the authors state that these mixtures have limited genetic consequences since signals of admixture with Europeans ...
Harris, H (1974). "Genetic heterogeneity in inherited disease". J Clin Pathol Suppl (R Coll Pathol). 8: 32-7. doi:10.1136/jcp. ... the prenatal diagnosis of disorders using genetic markers, the extensive heterogeneity of inherited diseases, and the mapping ... His work showed that human genetic variation was not rare and disease-causing but instead was common and usually harmless. He ... The main purpose of the Unit was to investigate the extent of genetic variation in healthy humans using family and population ...
"Implications of genetic heterogeneity in cancer". Annals of the New York Academy of Sciences. 1267 (1): 110-6. Bibcode: ... Genetic and epigenetic[edit]. There is a diverse classification scheme for the various genomic changes that may contribute to ... Knudson AG (November 2001). "Two genetic hits (more or less) to cancer". Nature Reviews. Cancer. 1 (2): 157-62. doi:10.1038/ ... Often, the multiple genetic changes that result in cancer may take many years to accumulate. During this time, the biological ...
"Implications of genetic heterogeneity in cancer". Ann. N. Y. Acad. Sci. 1267: 110-6. doi:10.1111/j.1749-6632.2012.06590.x. PMC ... These cells are presumed to be clonal - that is, they are derived from the same cell,[8] and all carry the same genetic or ... A neoplasm can be caused by an abnormal proliferation of tissues, which can be caused by genetic mutations. Not all types of ... For example, a renal cancer, sampled in 9 areas, had 40 ubiquitous mutations, demonstrating tumour heterogeneity (i.e. present ...
Zuckerlandl, Emile; Pauling, Linus B. (1962). "Molecular disease, evolution, and genetic heterogeneity". Horizons in ... Genetic diseases may be predicted by identifying sequences that are conserved between humans and lab organisms such as mice or ... Harris, J. K. (12 February 2003). "The Genetic Core of the Universal Ancestor". Genome Research. 13 (3): 407-412. doi:10.1101/ ... The GERP (Genomic Evolutionary Rate Profiling) framework scores conservation of genetic sequences across species. This approach ...
Schmitt MW, Prindle MJ, Loeb LA (September 2012). "Implications of genetic heterogeneity in cancer". Ann. N. Y. Acad. Sci. 1267 ... These cells are presumed to be clonal - that is, they are derived from the same cell, and all carry the same genetic or ... A neoplasm can be caused by an abnormal proliferation of tissues, which can be caused by genetic mutations. Not all types of ... March 2012). "Intratumor heterogeneity and branched evolution revealed by multiregion sequencing". N. Engl. J. Med. 366 (10): ...
"Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... Genealogical DNA test Genetic genealogy Human mitochondrial DNA haplogroup Human mitochondrial genetics Human mitochondrial ... 2009). "Out of Arabia-the settlement of island Soqotra as revealed by mitochondrial and Y chromosome genetic diversity" (PDF). ... 1999). "MtDNA analysis of Nile River Valley populations: A genetic corridor or a barrier to migration?". American Journal of ...
"Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... 2017). "Parallel palaeogenomic transects reveal complex genetic history of early European farmers". Nature. 551 (7680): 368-372 ... W3a1c W3a2 W3b W3b1 W4 W4a W5 W5a W5a1 W5a1a W5a1a1 W5a1a1a W5a2 W5b W6 C16192T W6a W6b W6c W7 Genealogical DNA test Genetic ...
"Genetic Heterogeneity of Heart-Hand Syndromes". Circulation. 91 (5): 1326-1329. doi:10.1161/01.CIR.91.5.1326. PMID 7867169. ... It is unknown if heart-hand syndromes are caused by shared or distinct genetic defects. It has been claimed that congenital ... "Heart-hand syndrome, Spanish type - Disease - Symptoms - Genetic and Rare Diseases Information Center (GARD) - an NCATS Program ... heart diseases are caused by a limited number of shared genetic defects. Holt-Oram syndrome, Brachydactyly-long thumb syndrome ...
Zuckerkandl, Emile; Pauling, Linus B. (1962). "Molecular disease, evolution, and genetic heterogeneity". In Kasha, M.; Pullman ... rather than for example genetic hitchhiking of a neutral allele due to genetic linkage with non-neutral alleles. After ... Levels of genetic diversity vary much less than census population sizes, giving rise to the "paradox of variation" . While high ... This view is based in part on the degenerate genetic code, in which sequences of three nucleotides (codons) may differ and yet ...
"Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... "ANALYSES OF GENETIC DATA WITHIN AN INTERDISCIPLINARY FRAMEWORK TO INVESTIGATE RECENT HUMAN EVOLUTIONARY HISTORY AND COMPLEX ... Genealogical DNA test Genetic genealogy Haplogroup K1a1b1a (mtDNA) Human mitochondrial genetics Population genetics Human ... Approximately 32% of people with Ashkenazi Jewish ancestry are in haplogroup K. This high percentage points to a genetic ...
Arias, S. (March 1971). "Genetic heterogeneity in the Waardenburg syndrome". Birth Defects Original Article Series. 07 (4): 87- ... "Waardenburg syndrome , Genetic and Rare Diseases Information Center (GARD) - an NCATS Program". rarediseases.info.nih.gov. ... Waardenburg syndrome is a group of rare genetic conditions characterised by at least some degree of congenital hearing loss and ... GeneReviews/NCBI/NIH/UW entry on Waardenburg Syndrome Type I OMIM Genetic disorder catalog - Waardenburg syndrome. ...
"Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... Recent genetic analysis of North African populations have found that, despite the complex admixture genetic background, there ... The genetic proximity observed between the North-Africans and Southern Europeans is due to the fact that both these groups ... June 2002). "Genetic Evidence for the Expansion of Arabian Tribes into the Southern Levant and North Africa". The American ...
Arias, S (1971). "Genetic heterogeneity in the Waardenburg's syndrome". Birth Defects B. 07 (4): 87-101. PMID 5006208. " ... Ahmed, M.; Ye, X.; Taub, P. (2016). "Review of the Genetic Basis of Jaw Malformations". Journal of Pediatric Genetics. 05 (4): ... Additionally, they arise because of genetic defects affecting the formation of neural crest and because of the action of ... There are four different types of Waardenburg's syndrome, each with distinct genetic and physiological features. Types I and II ...
Bekada A, Arauna LR, Deba T, Calafell F, Benhamamouch S, Comas D (September 24, 2015). "Genetic Heterogeneity in Algerian Human ... Genetic Patterns of Y-chromosome and Mitochondrial DNA Variation, with Implications to the Peopling of the Sudan (PDF) (Ph.D. ... Genealogical DNA test Genetic genealogy Human mitochondrial genetics Population genetics The Seven Daughters of Eve Behar et al ... Since the genetic analysis corroborates archaeological and literary evidence, it is believed that the excavated remains belong ...
... extreme genetic heterogeneity in North Africa". Journal of Human Genetics. 60 (1): 41-9. doi:10.1038/jhg.2014.99. PMID 25471516 ... "Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... Kujanová M, Pereira L, Fernandes V, Pereira JB, Cerný V (October 2009). "Near eastern neolithic genetic input in a small oasis ... "World Y-DNA frequencies". The Genetic Atlas. Bekada A, Fregel R, Cabrera VM, Larruga JM, Pestano J, et al. (2013) Introducing ...
Zuckerkandl, E.; Pauling, L. (1962). "Molecular Disease, Evolution and Genetic Heterogeneity". In Kasha, M.; Pullman, B. (eds ...
"Genetic heterogeneity among blue-cone monochromats". Am. J. Hum. Genet. 53 (5): 987-1000. PMC 1682301. PMID 8213841. Lewis, R A ...
"Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... Fadhlaoui-Zid K, Plaza S, Calafell F, Ben Amor M, Comas D, Bennamar El gaaied A (May 2004). "Mitochondrial DNA heterogeneity in ... Ingman M, Gyllensten U (2007). "A recent genetic link between Sami and the Volga-Ural region of Russia". European Journal of ... 2004). "The Western and Eastern Roots of the Saami-the Story of Genetic "Outliers" Told by Mitochondrial DNA and Y Chromosomes ...
"Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... Genealogical DNA test Genetic genealogy Population genetics Malyarchuk et al. (2008): "The main components of the middle Upper ... Martina Kujanova; Luisa Pereira; Veronica Fernandes; Joana B. Pereira; Viktor Cerny (2009). "Near Eastern Neolithic Genetic ... 2003). "Evidence for a genetic discontinuity between Neandertals and 24,000-year-old anatomically modern Europeans". ...
"Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... 2007). "Genetic Evidence of Modern Human Dispersals in South Asia". The Evolution and History of Human Populations in South ... 2003). "The genetic heritage of the earliest settlers persists both in Indian tribal and caste populations". American Journal ... These findings also highlight the importance of Indian subcontinent in the early genetic history of human settlement and ...
"Genetic Heterogeneity in Algerian Human Populations". PLOS ONE. 10 (9): e0138453. Bibcode:2015PLoSO..1038453B. doi:10.1371/ ... "Genetic Patterns of Y-chromosome and Mitochondrial DNA Variation, with Implications to the Peopling of the Sudan" (PDF). ... Soares P, Rito T, Pereira L, Richards M (March 2016). "A Genetic Perspective on African Prehistory" (PDF). Africa from MIS 6-2 ... "Near Eastern Neolithic Genetic Input in a Small Oasis of the Egyptian Western Desert". American Journal of Physical ...
... status of the singular African oriole finch Linurgus olivaceus and evolution and heterogeneity of the genus Carpodacus" (PDF). ... "Genetic relationships of North American cardueline finches" (PDF). Condor 88 (4): 409-420. doi:10.2307/1368266 ...
2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk". Thorax. 59 (3): 259 ... However, one particular site shows a considerable amount of heterogeneity since tri- and even tetraantennary N-glycans can be ... this causes the heterogeneity observed on normal A1AT when analysed by isoelectric focusing. Also, the fucosylated triantennary ... a new paradigm for hepatocellular carcinoma in genetic liver disease". Hepatology. 42 (3): 514-21. doi:10.1002/hep.20815. PMID ...
In 2012, a team of scientists from Johns Hopkins University published a genetic compression algorithm that does not use a ... For this, Chanda, Elhaik, and Bader introduced MAF based encoding (MAFE), which reduces the heterogeneity of the dataset by ... using both conventional compression algorithms and genetic algorithms adapted to the specific datatype. ...
"Evidence for further genetic locus heterogeneity and confirmation of RLS-1 in restless legs syndrome". Movement Disorders 21 (1 ... 2007). "A Genetic Risk Factor for Periodic Limb Movements in Sleep". New England Journal of Medicine 357 (7): 639-47. doi: ...
Pauling, L. y Zuckerkandl, E. (1962). "Molecular disease, evolution, and genic heterogeneity". Horizons in Biochemistry. ... "The genetic code" (PDF). Nobel Lecture (en inglés). nobelprize.org. Arquivado dende o orixinal (pdf) o 09 de xaneiro de 2009 ... "FDA Clears First of Kind Genetic Lab Test". FDA News (en inglés). FDA. Consultado o 13 de setembro de 2008 ... "Biochemical Method for Inserting New Genetic Information into DNA of Simian Virus 40: Circular SV40 DNA Molecules Containing ...
... the challenge of heterogeneity and the role of antigenic load". Experimental Gerontology. 34 (8): 911-921. doi:10.1016/S0531- ... to inversely repeat an evolutionary pattern and most of the parameters affected by immunosenescence appear to be under genetic ...
These rare genetic variants are autosomal dominant.[26] Cancer[edit]. In addition to its role in Alzheimer's disease, ... Larner AJ, Doran M (2006). "Clinical phenotypic heterogeneity of Alzheimer's disease associated with mutations of the ... "Genetic linkage evidence for a familial Alzheimer's seasesease locus on chromosome 14". Science. 258 (5082): 668-71. Bibcode: ...
Main article: Genetic pollution. Native species can be threatened with extinction[113] through the process of genetic pollution ... This increase in heterogeneity can create microclimates in sparse and eroded ecosystems, which then promotes the growth and ... Genetic Pollution from Farm Forestry using eucalypt species and hybrids; A report for the RIRDC/L&WA/FWPRDC]; Joint Venture ... For example, L. leucozonium, shown by population genetic analysis to be an invasive species in North America,[77] has become an ...
Genetic engineering[edit]. TATA box modification[edit]. Evolutionary changes have pushed plants to adapt to the changing ... fluorescence resonance energy transfer shows uniformity in TATA binding protein-induced DNA bending and heterogeneity in ...
Contemporary genetic technologies and female reproduction. Hum. Reprod. Update. 2011, 17 (6): 829-47. PMC 3191938. PMID ... Polycystic ovarian disease: heritability and heterogeneity. Hum. Reprod. Update. 2001, 7 (1): 3-7. PMID 11212071. doi:10.1093/ ... De Leo V, Musacchio MC, Cappelli V, Massaro MG, Morgante G, Petraglia F. Genetic, hormonal and metabolic aspects of PCOS: an ... McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. 12 September 2011 [15 November ...
International Conference on Genetic and Evolutionary Computation (combining the 20th International Conference on Genetic ... term was needed to distinguish between anonymous homogeneity in collective prediction systems and non-anonymous heterogeneity ... Algorithms ICGA and the 16th Annual Genetic Programming Conference. July 12-16. Dublin, Ireland. ...
... (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, ... In cases of allelic heterogeneity, the MIM number of the entry is followed by a decimal point and a unique 4-digit number ... A Catalog of Human Genes and Genetic Disorders. Baltimore, MD: Johns Hopkins University Press, 11th ed, 1994; 12th ed, 1998. ... MARRVEL, a website that uses OMIM as one of the six human genetic databases and seven model organism databases to integrate ...
Spiekerkoetter, U; Sun, B; Khuchua, Z; Bennett, MJ; Strauss, AW (June 2003). "Molecular and phenotypic heterogeneity in ... "Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression". PLoS ONE. 5 (9): e12862. doi:10.1371/ ... 2003). "Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations ...
Genetic diagnostic[edit]. Genetic tests may be useful in assessing whether a person has primary lactose intolerance. Lactase ... "Transcriptional heterogeneity in the lactase gene within cell-type is linked to the epigenome". Scientific Reports. 7 (1): ... This genetic defect is characterized by a complete lack of lactase (alactasia). About 40 cases have been reported worldwide, ... Genetic analysis shows lactase persistence has developed several times in different places independently in an example of ...
... role of plasticity and heterogeneity". TheScientificWorldJournal. 2014: 859817. doi:10.1155/2014/859817. PMC 3916026. PMID ... Other genetic factors are being investigated,[60] of which many are likely.[17] ... A person's genetic makeup also affects the risk.[9] ...
4.0 4.1 Joseph, J. (2003). The Gene Illusion: Genetic Research in Psychiatry and Psychology under the Microscope. PCCS Books. ... March 2006). "Heterogeneity in incidence rates of schizophrenia and other psychotic syndromes: findings from the 3-center AeSOP ... This may be both the result of stressful events because of the family member and possibly a genetic effect.[18] ...
March 2012). "Isolation, characterization, and genetic profiling of subpopulations of olfactory ensheathing cells from the ... "Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions". Cellular and Molecular Life ... genetic engineering, and therapeutic potential". Journal of Neurotrauma. 23 (3-4): 468-78. doi:10.1089/neu.2006.23.468. PMID ...
1993). „Genetic heterogeneity among blue-cone monochromats.". Am. J. Hum. Genet. 53 (5): 987-1000. PMC 1682301 . PMID 8213841. ...
The cause is not known in 90% to 95% of cases,[4] but is believed to involve both genetic and environmental factors.[13] The ... Chiò A, Calvo A, Moglia C, Mazzini L, Mora G (July 2011). "Phenotypic heterogeneity of amyotrophic lateral sclerosis: a ... ALS and frontotemporal dementia (FTD) are now considered to be part of a common disease spectrum (FTD-ALS) because of genetic, ... Despite a number of genetic and environmental studies, the cause of ALS/PDC remains unknown. Rates peaked in the early 1950s ...
These are good sources for information on the genetic heritage of the Tuareg and their relatedness to other populations. ... 2010) in a study of 90 unrelated individuals observed greater matrilineal heterogeneity among the Tuareg inhabiting more ... a genetic survey of their paternal heritage". Am J Phys Anthropol. 145 (1): 118-24. doi:10.1002/ajpa.21473. PMID 21312181.. ... 1998) "Mitochondrial DNA analysis of northwest African populations reveals genetic exchanges with European, near-eastern, and ...
Möller, M; Hoal, EG (2010). "Current findings, challenges and novel approaches in human genetic susceptibility to tuberculosis ... but data are difficult to interpret because of heterogeneity in the results across studies.. Cite uses deprecated parameter , ... "Genetic Biodiversity of Mycobacterium tuberculosis Complex Strains from Patients with Pulmonary Tuberculosis in Cameroon". J. ...
Some HLA alleles have been suspected along with complement phenotypes as being genetic factors. Non-aggressive Berger's disease ... which hardly produce statistically significant evidence regarding the heterogeneity of IgA nephropathy patients, the diversity ...
Single-cell resolution can uncover the roles of genetic mosaicism or intra-tumor genetic heterogeneity in cancer development or ... reveals non-genetic gene-expression heterogeneity". Genome Biology. 14 (4): R31. doi:10.1186/gb-2013-14-4-r31. PMC 4054835. ... Single-nucleotide polymorphisms (SNPs), which are a big part of genetic variation in the human genome, and copy number ... Pooling single cells is one strategy to increase methylome coverage, but at the cost of obscuring the heterogeneity in the ...
Gilbody S, Lewis S, Lightfoot T (2007). "Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric ... "Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity". J Epidemiol Community Health ... some genetic disorders that affect levels of folate; and certain medicines (such as phenytoin, sulfasalazine, or trimethoprim- ...
The strength of genetic drift depends on the population size. If a population is at a constant size with constant mutation rate ... But selection, demographic fluctuations and other violations of the neutral model (including rate heterogeneity and ... Tajima's D is a population genetic test statistic created by and named after the Japanese researcher Fumio Tajima.[1] Tajima's ... The two quantities whose values are compared are both method of moments estimates of the population genetic parameter theta, ...
In particular, the authors' treatment of 'heterogeneity bias' clarifies the importance of addressing both 'within' and 'between ... "Does neighbourhood deprivation affect the genetic influence on body mass?". Social Science & Medicine. 185: 38-45. doi:10.1016 ... Duncan, Craig; Jones, Kelvyn (2010). "Using Multilevel Models to Model Heterogeneity: Potential and Pitfalls". Geographical ... Duncan, Craig; Jones, Kelvyn; Moon, Graham (1998). "Context, composition and heterogeneity: Using multilevel models in health ...
Naeem, S (1988). "Resource heterogeneity fosters coexistence of a mite and a midge in pitcher plants". Ecological Monographs. ... noting the genetic evidence for multiple independent plant lines that evolved a fully carnivorous habit (Juniper et al., 1989; ...
... source of the protein can be either natural or produced in a production system using recombinant DNA techniques through genetic ... number of peaks is present and thus to identify possible problems due to multiple conformations or sample heterogeneity. The ...
Domestication is also studied by using the genetic material of present-day horses and comparing it with the genetic material ... "Allelic Heterogeneity at the Equine KIT Locus in Dominant White (W) Horses". PLoS Genetics. 3 (11): e195. doi:10.1371/journal. ... These include the lateral rack, running walk, and tölt as well as the diagonal fox trot.[85] Ambling gaits are often genetic in ... Current genetic tests can identify at least 13 different alleles influencing coat color,[44] and research continues to discover ...
... the influence of the degree of heterogeneity of the prepared hybrid composites ought to be studied.The different physical and ... Genetic material. Contents. *1 Classification of materials. *2 See also. *3 References ...
Genetic heterogeneity in sporadic colorectal adenomas.. Saraga E1, Bautista D, Dorta G, Chaubert P, Martin P, Sordat B, Protiva ... This study demonstrates the presence of genetic heterogeneity in colorectal adenomas and supports the notion that K-ras ... This observation suggests that the prevalence of genetic mutations and of aneuploidy is probably underestimated, as generally ... Tumourigenesis is generally considered a multistep process in which multiple genetic alterations occur, eventually reflected in ...
... genetic inheritance" in the popular press. This supposed genetic homogeneity was a major factor in the establishment of deCODE ... It is doubtful that population changes during past calamities had much effect on the genetic variability of Icelanders. ... In fact, it is mainly because mtDNA is a non-recombining genetic unit that many errors are easily identified by phylogenetic ... Professor Árnason explains in his article: "Recently, statements have been made about a special genetic homogeneity of the ...
Despite the marked genetic heterogeneity of heart-hand syndromes, genetic heterogeneity of Holt-Oram syndrome itself is at most ... Genetic Heterogeneity of Heart-Hand Syndromes. Craig T. Basson, Scott D. Solomon, Barbara Weissman, Calum A. MacRae, Andrew K. ... Genetic Heterogeneity of Heart-Hand Syndromes. Craig T. Basson, Scott D. Solomon, Barbara Weissman, Calum A. MacRae, Andrew K. ... Genetic Heterogeneity of Heart-Hand Syndromes. Craig T. Basson, Scott D. Solomon, Barbara Weissman, Calum A. MacRae, Andrew K. ...
Initial research on genetic heterogeneity was conducted using genetic linkage analyses, which map genetic loci of related ... Genetic heterogeneity occurs through the production of single or similar phenotypes through different genetic mechanisms. There ... Disorders on the Autism spectrum have high levels of genetic heterogeneity and result from multiple genetic pathways including ... Marked genetic heterogeneity is correlated to multiple levels of causation in many common human diseases including cystic ...
Genetic and epigenetic heterogeneity (the main form of non-genetic heterogeneity) are key elements in cancer progression and ... Genetic and epigenetic heterogeneity in cancer: a genome-centric perspective.. Heng HH1, Bremer SW, Stevens JB, Ye KJ, Liu G, ... of heterogeneity to establish genetic and epigenetic patterns. In particular, the appreciation of new types of epigenetic ... In this mini-review, we have briefly analyzed a number of mis-conceptions regarding cancer heterogeneity, followed by the re- ...
Genetic heterogeneity among Eurytemora affinis populations in Western Europe. *Gesche Winkler. 1. , ... Winkler, G., Souissi, S., Poux, C. et al. Genetic heterogeneity among Eurytemora affinis populations in Western Europe. Mar ... Winkler G, Dodson JJ, Lee CE (2008) Heterogeneity within the native range: population genetic analyses of sympatric invasive ... To gain information on genetic subdivision and to evaluate heterogeneity among European populations, we analyzed samples from 8 ...
... to argue for the relative genetic heterogeneity of Icelanders in his analysis of mitochondrial DNA (mtDNA) sequences, are poor ... This latest research article, A Reassessment of Genetic Diversity in Icelanders: Strong Evidence from Multiple Loci for ... and uses population genetics simulations to demonstrate that genetic drift, not admixture (as claimed by E. Árnason), has been ... both greatly expands sample sizes from individual populations and the number of genetic loci analysed, ...
Finally, we illustrate how the operation of well-known genetic circuits is impacted by spatial effects. ... model that can be used to both analyze and design genetic circuits while accounting for spatial intracellular effects. We apply ... and should be considered but also where a traditional well-mixed model suffices despite severe spatial heterogeneity. ... Author summary A general and simple modeling framework to determine how spatial heterogeneity modulates the dynamics of gene ...
... Hum Mutat. 2000;16(1):23-30. doi: 10.1002/1098-1004(200007)16:1,23::AID-HUMU5, ... These data suggest the presence of significant genetic heterogeneity for PJS and the involvement of other loci in this syndrome ... Additionally, linkage analyses have suggested a modicum of genetic heterogeneity, with the majority of PJS families showing ... Long-range PCR was used for the detection of larger genetic insertions or deletions. Mutation analysis revealed genetic ...
Future human genetic studies, both with a focus on population and medical genetics, will have to consider differences in ... These observations, also corroborated by f3 migration statistics and other approaches, indicate genetic continuity of and ... we show that the Iranian population comprises distinct genetic variation with respect to populations in close geographic ... heterogeneity, consanguinity and degree of admixture between the ethnic groups for an adequate design and interpretation. ...
... potentially stemming from substantial genetic heterogeneity. All current known pathog … ... Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. ... WNT Signaling Perturbations Underlie the Genetic Heterogeneity of Robinow Syndrome Am J Hum Genet. 2018 Jan 4;102(1):27-43. doi ... Contrary to the view that non-allelic genetic heterogeneity hampers gene discovery, this study demonstrates the utility of rare ...
Genetic Heterogeneity in Familial Juvenile Polyposis. Sherry C. Huang, Christine R. Chen, Joel E. Lavine, Sharon F. Taylor, ... Genetic Heterogeneity in Familial Juvenile Polyposis. Sherry C. Huang, Christine R. Chen, Joel E. Lavine, Sharon F. Taylor, ... Genetic Heterogeneity in Familial Juvenile Polyposis. Sherry C. Huang, Christine R. Chen, Joel E. Lavine, Sharon F. Taylor, ... Genetic Heterogeneity in Familial Juvenile Polyposis Message Subject (Your Name) has forwarded a page to you from Cancer ...
TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes. Maria J. Redondo, Susan Geyer, Andrea K. ... TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes. Maria J. Redondo, Susan Geyer, Andrea K. ... TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes Message Subject (Your Name) has forwarded a ... Our data provide a genetic explanation for some of the heterogeneity of the disease manifestations and support the concept of ...
Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing, gDNA Enrichment ... and Genetic Analysis, Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles, ... Genetic Barcoding with Fluorescent Proteins for Multiplexed Applications, Purifying the Impure: Sequencing Metagenomes and ... Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers, ...
This review aims to provide an insight on how HCC heterogeneity influences the different primary mechanisms of chemoresistance ... Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity by Loraine Kay D. Cabral ... "Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity." Cancers 12, no. 6: 1576. ... Sorafenib Resistance in Hepatocellular Carcinoma: The Relevance of Genetic Heterogeneity. Cancers. 2020; 12(6):1576. ...
Assessment of Genetic Heterogeneity in Structured Plant Populations Using Multivariate Whole-Genome Regression Models. ... Because the extent of genetic heterogeneity in this data set is large, in general, the W- and MG-GBLUPs performed either ... From a prediction perspective, the choice of method seems to depend on the extent of genetic heterogeneity and on sample size. ... Assessment of Genetic Heterogeneity in Structured Plant Populations Using Multivariate Whole-Genome Regression Models. ...
The spatial genetic structuring of the land snail Helix aspersawas investigated for 32 colonies within an intensive ... Metapopulation genetic structure and migration pathways in the land snail Helix aspersa: influence of landscape heterogeneity. ... Measures of genetic similarity and genetic distance. In: Studies in Genetics VII, pp. 145-153. University of Texas, Publication ... Genetic divergence was assessed using either classical IAM-based statistics, or SMM-based genetic distances specifically ...
Masahito Hosokawa] Massively parallel single-cell genomics for elucidation of intra-tissue genetic heterogeneity. ... Masahito Hosokawa] Massively parallel single-cell genomics for elucidation of intra-tissue genetic heterogeneity ... to elucidate intra-tissue genetic heterogeneity at the single-cell resolution. Most tumors display extensive intra-tumor ... For understanding these intra-tissue heterogeneities, ideal single-cell genomics methods should analyze tens of thousands of ...
... genetic variants contribute to phenotypic heterogeneity of type 1 diabetes, according to a study published online Oct. 12 in ... Genetic variants tied to type 1 diabetes heterogeneity. November 27, 2017 (HealthDay)-Transcription factor 7 like 2 (TCF7L2) ... Genetic data help ID risk of future impaired fasting glucose. June 16, 2016 (HealthDay)-The addition of genetic risk variant ... genetic variants contribute to phenotypic heterogeneity of type 1 diabetes, according to a study published online Oct. 12 in ...
Modeling the impact of genetic heterogeneity on immunotherapy Message Subject. (Your Name) has forwarded a page to you from ... Furthermore, HGSOC is characterized by extensive genomic heterogeneity, and the impact of this heterogeneity on the immune ...
... Author(s). Li, Amy, Ph ... Taken together, our insight on the evolution of CD4+ T cell heterogeneity in tumors provides a window into the natural history ... Through IL-33 administration and Treg-specific genetic ablation of ST2 we find that IL-33 signaling may be necessary and ... and Tregs in an inducible genetic mouse model of lung adenocarcinoma. We show that lung tumor-associated Tregs have a distinct ...
Instability in Oncogenesis Directly Implicates Mutator Phenotype Progression through Genetic Lesion Heterogeneity Lawrence M ... Instability in Oncogenesis Directly Implicates Mutator Phenotype Progression through Genetic Lesion Heterogeneity. Adv Cancer ... Per se heterogeneity is an inherently defining signature characteristic of the oncogenic pathways within an individual tumor ... The key attribute of marked heterogeneity in genomic lesions attests for the essential evolution of the mutator phenotype per ...
Epistasis and genetic variance heterogeneity are two non-additive genetic inheritance patterns that are often, but not always, ... and genetic variance heterogeneity, and a brief discussion about how genetic processes other than epistasis can also give rise ... Epistasis, gene action, genetic variance heterogeneity, genotype-phenotype maps, non-additive, quantitative genetics HSV ... On the relationship between epistasis and genetic variance heterogeneity.. Forsberg, Simon K. G. Uppsala universitet, ...
... Sanna, Adriana LU ; Harbst, Katja LU ; Johansson, Iva LU ... However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. ... However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. ... However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. ...
TODAY Adrian Seminar - Physiological and genetic heterogeneity in hearing loss. Add to your list(s) Download to your calendar ... suggesting extreme genetic heterogeneity with around 1,000 genes predicted to be involved in hearing impairment. Some mutant ... We took a genetic approach to identify new molecules involved in hearing loss by screening a large cohort of newly-generated ... University of Cambridge , Talks.cam , Adrian Seminars in Neuroscience , TODAY Adrian Seminar - Physiological and genetic ...
Conclusions: These results support the hypothesis that the aetiology of ICP is heterogeneous and that ICP is due to a genetic ... Background and aims: The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy ( ... Jacquemin E, Hadchouel M. Genetic basis of progressive familial intrahepatic cholestasis. J Hepatol1999;31:377-81. ... The results of molecular genetic analysis further suggest that the previously identified three cholestasis genes are not likely ...
Expanding the genetic heterogeneity of intellectual disability. Access & Citations. * 4368 Article Accesses. ...
Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized ... Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized ... We have used complementation analysis after somatic cell fusion to investigate the genetic relationships among various genetic ...
Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms ... Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in ... Evidence that genetic variants in FGFR2 may influence tumor subtype is provided by the fact that susceptibility loci in FGFR2 ... J. R. Palmer, E. A. Ruiz-Narvaez, C. N. Rotimi et al., "Genetic susceptibility loci for subtypes of breast cancer in an African ...
Genetic heterogeneity of hepatitis C virus in association with antiviral therapy determined by ultra-deep sequencing. * * Nasu ... Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic ... Conclusion : Use of the ultra-deep sequencing technology revealed massive genetic heterogeneity of HCV, which has important ... and unveiled extremely high genetic heterogeneity in the genotype 1b HCV population. There was no significant difference in the ...
  • Most tumors display extensive intra-tumor heterogeneity, with various subpopulations of cells contains different mutations. (go.jp)
  • Taken together, our insight on the evolution of CD4+ T cell heterogeneity in tumors provides a window into the natural history of tumor immunosuppression and may reveal critical mediators of the tumor immune response. (mit.edu)
  • Mutator mutations are generally considered cooperative pathways associated with the high degrees of heterogeneity of tumors. (omicsonline.org)
  • Therefore, determining whether genetic risk factor associations for breast cancer differ by subtype of the tumors represents a critical etiologic question. (hindawi.com)
  • Many lines of evidence indicate a strong genetic component to the development of these tumors. (oup.com)
  • To define HER2 genetic heterogeneity and to provide practice guidelines for examining and reporting breast tumors with genetic heterogeneity for improvement of HER2 testing in breast cancer. (elsevier.com)
  • Due to their low incidence and the existence of multiple morphologically defined subtypes, these tumors are still poorly understood with regard to their molecular pathogenesis and therapeutically relevant genetic alterations. (oncotarget.com)
  • However, it remains critical to establish how the immune system affects the clonal heterogeneity of tumors that often display cell-to-cell variation in genetic alterations and antigenic expression. (sciencemag.org)
  • Alzheimer's disease is a complicated neurodegenerative disorder with multiple phenotypic subtypes, including clinical and preclinical, that result from different genetic origins. (wikipedia.org)
  • 1 2 Elucidation of the genetic etiologies of these autosomal dominant heart-hand syndromes will improve diagnosis and management of a complex group of disorders with highly variable phenotypic expression. (ahajournals.org)
  • HealthDay)-Transcription factor 7 like 2 ( TCF7L2 ) genetic variants contribute to phenotypic heterogeneity of type 1 diabetes, according to a study published online Oct. 12 in Diabetes Care . (medicalxpress.com)
  • We subsequently use this framework to demonstrate how stochasticity generates complex behavior and phenotypic heterogeneity in the case of an artificial lac operon genetic network, characteristic of positive feedback regulation. (rice.edu)
  • Our results show that stochasticity can enhance phenotypic heterogeneity, create or destroy bistability, and result in noise-induced transitions between attracting vicinities. (rice.edu)
  • We aim to determine the yield from genetic testing strategies and the genetic and phenotypic spectrum of HCA in Australia by analysing real-world data. (springer.com)
  • In this study, phenotypic data were pooled across multiple research stations to facilitate investigation of the genetic and nongenetic components of feed efficiency in Holstein cattle. (sigmaaldrich.com)
  • JS demonstrates substantial phenotypic variability and genetic heterogeneity. (bmj.com)
  • This study provides a comprehensive view of the current genetic basis, phenotypic range and gene-phenotype associations in JS. (bmj.com)
  • The results of the studies on genetic diversity, phenotypic traits, and distribution allow us to assume that the detected groups are incipient allopatric (geographical) species. (deepdyve.com)
  • In this Review, we discuss how some of the latest advances in the genetics of ASD have facilitated parsing of the phenotypic heterogeneity of this disorder. (escholarship.org)
  • Objective: To report a detailed phenotypic and genetic analysis of a patient cohort with sequence variations in BEST1. (ox.ac.uk)
  • This observation suggests that the prevalence of genetic mutations and of aneuploidy is probably underestimated, as generally only one sample is investigated. (nih.gov)
  • and locus heterogeneity, which occurs when a similar phenotype is produced by mutations at different loci. (wikipedia.org)
  • Driver oncogenic mutations presumably progress with expansion of clonally selected subpopulations of tumor cells in a manner that calls into operative modes the development of genetic instability. (omicsonline.org)
  • Our results show that NIPBL mutations are present in only 35% of CdLS cases, strongly suggesting the genetic heterogeneity of this syndrome. (bmj.com)
  • Although mutations in known driver genes including TP53, PIK3CA , and GATA3 were preferentially clonal in both sites, primary breast cancers and their synchronous metastases displayed spatial intratumor heterogeneity. (aacrjournals.org)
  • 253 different mutations in 23 genes highlight the extreme genetic heterogeneity of JS. (bmj.com)
  • Two approaches were adopted: (i), determination of frequency and nature of mutations in KA-ras and (ii), determination of the nature and extent of genetic aberrations, at chromosomal level, in advanced colorectal cancer. (gla.ac.uk)
  • Multiple sampling revealed frequent heterogeneity within carcinomas: 9 of 26 primaries with Ki-ras mutations also contained areas of carcinoma with only the wild-type gene, implying that Ki-ras mutation, even when present in a colonic carcinoma, may not have been necessary for establishing the malignant phenotype. (gla.ac.uk)
  • The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. (biomedcentral.com)
  • The current study, in the aim of further clarifying the genetic origin of implants, assessed BRAF/KRAS hot spot mutations and the p53/p16 INK4a immunophenotype of s-BOTs and corresponding implants (n = 49) of 15 patients by pyro-sequencing and immunostaining, respectively. (biomedcentral.com)
  • Unfortunately for many cancers the confusing heterogeneity of underlying mutations leading to similar cancer phenotypes has precluded the ability to design targeted ID1 therapies that are effective in a large percentage of cancer patients. (acmbcb.org)
  • Models that accurately reflect this genetic heterogeneity and allow it to be understood are desperately needed to identify driver mutations and design rational targeted therapies. (acmbcb.org)
  • These transposon-based systems therefore represent powerful genetic tools for identifying cancer-promoting mutations. (acmbcb.org)
  • WWS shows a unexpected high level of genetic heterogeneity and mutations in 12 different genes, all engaged in the O-glycosylation of α‎DG, have been connected to WWS so far. (oxfordmedicine.com)
  • Heterogeneity in the granulomatous response to mycobacterial infection in patients with defined genetic mutations in the interleukin 12-dependent interferon-gamma production pathway. (lshtm.ac.uk)
  • This supposed genetic homogeneity was a major factor in the establishment of deCODE Genetics, the biotechnology company set up in Iceland in 1996 to map disease genes in the Icelandic population. (innovations-report.com)
  • 69 genes and 145 loci have been discovered to be involved in the genetic heterogeneity of non-syndromic hearing loss, and the phenotype of the disorder is largely associated with its pattern of inheritance. (wikipedia.org)
  • The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. (jove.com)
  • This sensitive electrophysiological test revealed 38 unexpected genes associated with raised thresholds from our unbiased sample of 1,211 genes tested, suggesting extreme genetic heterogeneity with around 1,000 genes predicted to be involved in hearing impairment. (cam.ac.uk)
  • The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known cholestasis genes ( BSEP , FIC1 , and MDR3 ) on the development of this disease. (bmj.com)
  • The results of molecular genetic analysis further suggest that the previously identified three cholestasis genes are not likely to be implicated in these Finnish ICP families with dominant inheritance. (bmj.com)
  • One idea-allelic heterogeneity, where genes each harbor multiple different causative variants-has received little attention, because it is difficult to detect with most genetic mapping designs. (prolekare.cz)
  • However, because of the technological limitations in clinical diagnostics, mainly resulting from the large size of many genes and the high cost of Sanger sequencing, many hearing-impaired individuals with familial HL do not know the genetic cause of their HL. (biomedcentral.com)
  • The results underscore the extensive genetic heterogeneity underlying non-syndromic LSLs, and posit potential novel candidate genes and complex modes of inheritance in this important group of birth defects. (biomedcentral.com)
  • Additionally, we performed multiregional, targeted next-generation sequencing (NGS) of adenomas and unmasked extensive heterogeneity, affecting known drivers such as APC, KRAS and mismatch repair (MMR) genes. (le.ac.uk)
  • Importantly transposons can be used as both forward and reverse genetic tools to elucidate cancer genes (transposon system consists of two parts: firstly a transposon vector containing any DNA sequence that is flanked by inverted repeat/direct terminal Ezetimibe repeat (IR/DR) sequences and secondly the transposase enzyme that is responsible for excision and reintegration of the transposon placed under the control of a promoter. (acmbcb.org)
  • T2/Onc combined with transgenes ubiquitously expressing transposase in wild-type or cancer predisposed mice induced or accelerated sarcoma and T-cell leukemia [2 3 In both cases the insertion sites are readily cloned and can be characterized rapidly to implicate new genes in solid tumor development using a forward genetic approach. (acmbcb.org)
  • Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. (oup.com)
  • This thesis comprises three studies that use statistical analysis of individual differences to unravel the genetic contribution of genes central to alpha-synuclein (-syn), tau, and noradrenergic pathologies to cognitive outcomes in a Western Australian community-based PD cohort. (edu.au)
  • Our findings illustrate a high level of etiological heterogeneity for deafness in the family and highlight some of the pitfalls of genetic analysis of large genes in extended pedigrees, when homozygosity for a single mutant allele is expected. (uchile.cl)
  • However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. (lu.se)
  • In the latest issue of Genome Medicine, scientist Anita Sveen and colleagues publish the largest multilevel genetic analysis of this tumor type reported to date, describing substantial inter- and intra-tumor heterogeneity. (uio.no)
  • Initial research on genetic heterogeneity was conducted using genetic linkage analyses, which map genetic loci of related individuals to identify genomic differences. (wikipedia.org)
  • These data suggest the presence of significant genetic heterogeneity for PJS and the involvement of other loci in this syndrome. (nih.gov)
  • The identification of extrinsic barriers to migration and their impact on the genetic distribution was addressed through the genotyping of 580 individuals using a combined set of enzyme and microsatellite loci. (springer.com)
  • Recently, large genome-wide association studies (GWAS) have identified nearly 70 genetic susceptibility loci associated with breast cancer risk [ 1 - 7 ]. (hindawi.com)
  • Evidence that genetic variants in FGFR2 may influence tumor subtype is provided by the fact that susceptibility loci in FGFR2 have stronger associations for estrogen receptor positive disease (ER+) than ER− [ 13 ]. (hindawi.com)
  • Here we make use of a panel of Drosophila melanogaster lines derived from multiple founders, allowing us to directly test for the presence of multiple alleles at a large set of genetic loci influencing gene expression. (prolekare.cz)
  • We find that the vast majority of loci harbor more than two functional alleles, demonstrating extensive allelic heterogeneity at the level of gene expression and suggesting that such heterogeneity is an important factor determining the genetic basis of complex trait variation in general. (prolekare.cz)
  • The mechanism by which these genetic loci cause PCOS has yet to be determined. (prolekare.cz)
  • In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC. (oup.com)
  • Se analizaron 30 loci con electroforesis en gel de almidón. (scielo.org.mx)
  • In particular, resources that have a well-defined multi-haplotype structure can be used to identify the extent of allelic heterogeneity [22] owing to the ability to estimate trait means for each haplotype at each mapped QTL. (prolekare.cz)
  • Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. (harvard.edu)
  • Árnason concludes "claims about a special genetic homogeneity of Icelanders relative to European populations would be suspect to the extent that they depended on anomalous data instead of the primary data. (innovations-report.com)
  • However, the fine scale geographic distribution, levels of genetic subdivision, evolutionary, and demographic histories of European populations have been less explored. (springer.com)
  • To gain information on genetic subdivision and to evaluate heterogeneity among European populations, we analyzed samples from 8 locations from 58° to 45°N and 0° to 23°E, using 549 base pairs of the mitochondrial cytochrome oxidase subunit I (COI) gene. (springer.com)
  • Interestingly, genetic structure varied distinctively among the three lineages: the East Atlantic lineage was divided between the Gironde and the Loire populations, the NSEC lineage comprised one single population unit spanning the Seine, Scheldt and Elbe rivers and the third lineage was restricted to the Baltic Proper (Sweden). (springer.com)
  • Moreover, these simulations also reveal that the summary statistics (gene diversity and mean pairwise mutational differences) used by E. Árnason, to argue for the relative genetic heterogeneity of Icelanders in his analysis of mitochondrial DNA (mtDNA) sequences, are poor comparative measures of genetic diversity in closely related populations such as those of Iceland and other European countries. (innovations-report.com)
  • In this article we address the problem of analyzing data from heterogeneous plant breeding populations, using three approaches: (a) a model that ignores population structure [A-genome-based best linear unbiased prediction (A-GBLUP)], (b) a stratified ( i.e. , within-group) analysis (W-GBLUP), and (c) a multivariate approach that uses multigroup data and accounts for heterogeneity (MG-GBLUP). (genetics.org)
  • It is further to the dimensions of susceptibility ratios when contrasted with normal surrounding tissues that the tumorigenesis phenomenon both envelopes and further incorporates the varied heterogeneity of tumor cell sub-populations within a given neoplastic lesion. (omicsonline.org)
  • During the past decades, several approaches have been used to model heterogeneity in bacterial cell populations, each approach focusing on different source(s) of heterogeneity. (rice.edu)
  • In this work we present a mathematical and computational framework that describes single cells or cell populations and takes into account stochasticity in reaction, division and DNA duplication, all of which constitute sources of cell population heterogeneity. (rice.edu)
  • This observation suggests that the genetic background of amyotrophic lateral sclerosis differs between different populations, countries and regions. (bmj.com)
  • Spatio-temporal changes in genetic structure among populations provide crucial information on the dynamics of secondary spread for introduced marine species. (csic.es)
  • Analyses of genetic differentiation and distribution of molecular variance revealed strong genetic structure, with significant differences among many populations, but no significant differences among years. (csic.es)
  • In these environments, the episodic chance arrival of colonisers appears to determine the genetic structure of harbour populations and the genetic composition of these early colonising individuals persists in the respective harbours, at least over moderate time frames (five years) that encompass ca. 20 generations of S. plicata. (csic.es)
  • Dissolved oxygen experiments in the laboratory showed significant clonal differences in low oxygen tolerance and hemoglobin synthesis implying that low dissolved oxygen concentrations in nature may be an important selective pressure affecting the spatial and temporal genetic heterogeneity in planktonic cladoceran populations. (illinois.edu)
  • In addition, a genetic risk score based on SNPs not individually associated with PCOS was found to be significantly associated with PCOS in Caucasian subjects [ 10 ], suggesting that some or all of the variants identified in Chinese populations are likely also risk variants in Caucasians. (prolekare.cz)
  • Local populations of the spiny pocket mice, Liomys pictus , were sampled from the tropical deciduous and semideciduous forests from Chamela, Jalisco, Mexico, where L. pictus experiences profound population fluctuations and high rates of population turnover, associated with the strong environmental seasonality and heterogeneity characteristic of these forests. (scielo.org.mx)
  • The evolution of these heteroplasmic populations through development, ageing, and generations is central to genetic diseases, but is poorly understood in mammals. (nature.com)
  • Although most genetic variation is common to all populations, genetic variants exist that are unique to specific SIRE groups ( 12 ). (aacrjournals.org)
  • It is doubtful that population changes during past calamities had much effect on the genetic variability of Icelanders. (innovations-report.com)
  • Different connectivity networks and geographical distances based on landscape features were constructed to evaluate the effect of environmental heterogeneity and to test the adequacy of an isolation by distance model on the distribution of the genetic variability. (springer.com)
  • Thus, genetic heterogeneity, with an overlap of different phenotypes, and the variability of hereditary patterns, raise the questions whether there is a morphological trait from dilated/hypertrophic cardiomyopathy to LVNC and what are the triggers and modifiers to develop either dilated, hypertrophic cardiomyopathy, or LVNC in patients with the same mutation. (uzh.ch)
  • In order to study the degree of genetic variability of strains isolated in Costa Rica, sequence data obtained from the 5′ non coding region from 7 patients from Costa Rica were compared with published sequences from 57 strains of all types. (deepdyve.com)
  • Host and viral-related factors (viral load, and genetic variability in the E1-E2, core and Interferon Sensitivity Determining Region) were assessed. (figshare.com)
  • The short-term changes in genetic variability, as a response to the fluctuations in population density and high rates of population turnover, together with movement of individuals (a marked male-biased dispersal was observed), could conceal or buffer divergences between these subpopulations. (scielo.org.mx)
  • In contrast, population and evolutionary genetics research has examined genetic variability within and between members of SIRE groups. (aacrjournals.org)
  • Nonetheless, these and other data support the notion that correlations between genomic variability and SIRE exist, and thus refute those who reject any genetic basis to race or ethnicity. (aacrjournals.org)
  • Compared to the degree of heterogeneity, individual molecular pathways will have limited predictability during stochastic cancer evolution where genome dynamics (reflected by karyotypic heterogeneity) will dominate. (nih.gov)
  • Robinow syndrome is a skeletal disorder historically refractory to molecular diagnosis, potentially stemming from substantial genetic heterogeneity. (nih.gov)
  • This review aims to provide an insight on how HCC heterogeneity influences the different primary mechanisms of chemoresistance against sorafenib including reduced drug intake, enhanced drug efflux, intracellular drug metabolism, alteration of molecular targets, activation/inactivation of signaling pathways, changes in the DNA repair machinery, and negative balance between apoptosis and survival of the cancer cells. (mdpi.com)
  • Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes. (lu.se)
  • For molecular genetic analysis, 16 individuals from two independently ascertained Finnish ICP families were genotyped for the flanking markers for BSEP , FIC1 , and MDR3 . (bmj.com)
  • Molecular genetic analysis also excluded linkage to the DYT6 locus and the GAG deletion in DYT1 , suggesting at least one additional RDP gene. (bmj.com)
  • In summary, our data provide novel insight into the fundamental molecular heterogeneity of salivary gland cancer, relevant in terms of tumor classification and the establishment of targeted therapeutic concepts. (oncotarget.com)
  • Our results generally correlate with previously reported genetic and molecular data and support the conclusion that S. bayanus should be reinstated as a separate taxon. (microbiologyresearch.org)
  • The present study investigated the evolution, intra-genotype heterogeneity and dispersal of cosmopolitan genotype to understand unique genetic characteristics that have shaped the molecular epidemiology and distribution of cosmopolitan lineages. (nature.com)
  • Modern descriptions of biological evolution will typically elaborate on major contributing factors to evolution such as the formation of local micro-environments, mutational robustness, molecular degeneracy , and cryptic genetic variation. (wikipedia.org)
  • The concepts of ethnicity, ancestry, and race are widely used in molecular epidemiologic research, often based on the assumption that these correlate (however roughly) with increased genetic homogeneity among people claiming a similar identity. (aacrjournals.org)
  • Our findings highlight the genetic heterogeneity of HCAs and support the use of NGS approaches for individuals who were negative on repeat expansion testing. (springer.com)
  • These studies highlight the genetic heterogeneity that exists within breast cancers in space and time. (biomedcentral.com)
  • Examination of the published literature on blood group and allozyme variation did not provide any support for the notion of special genetic homogeneity of the Icelanders, and further studies of microsatellite variation are unlikely to do so. (innovations-report.com)
  • Heterogeneity in genetic and nongenetic variation and energy sink relationships for residual feed intake across research stations and countries. (sigmaaldrich.com)
  • Much of the genetic variation underlying whole organism phenotypes is thought to be due to regulatory variation, i.e., variants influencing gene expression [23] - [26] . (prolekare.cz)
  • Increasingly, expression quantitative trait locus (eQTL) mapping is being used to identify the source of genetic variation in transcript abundances with the ultimate goal of linking variation at the nucleotide level to variation in gene expression and to variation in visible phenotypes. (prolekare.cz)
  • The evolutionary and ecological implications of these data are discussed in reference to the maintenance of genetic variation in heterogeneous environments. (illinois.edu)
  • The Genetic Basis of Mutation Rate Variation in Yeast. (escholarship.org)
  • These results highlight the role of tau pathology in PD cognition even in its early stages, possibly via different pathways (directly via the MAPT genetic variation, and indirectly via deregulation of tau via DYRK1A ). (edu.au)
  • In order to review the hypothesis stating that the level of genetic variation in a population is correlated with the degree of environmental heterogeneity, the genetic differences between subpopulations from these two contrasting habitats were evaluated. (scielo.org.mx)
  • Genetic variation in ICF syndrome: Evidence for genetic heterogeneity. (ru.nl)
  • Methods and Results Clinical evaluations and genetic linkage analyses were performed in five additional kindreds with Holt-Oram syndrome and also in one kindred with heart-hand syndrome type III and one kindred with familial atrial septal defect and conduction disease. (ahajournals.org)
  • To determine if the cardiac and/or limb abnormalities found in other heart-hand syndromes or in partial phenocopy syndromes are also due to a gene defect on chromosome 12q2, we have applied genetic linkage analysis to kindreds affected by Heart-Hand syndrome Type III or familial ASD with conduction disease. (ahajournals.org)
  • 7- 9 Familial clustering and uneven geographical distribution also indicate the genetic basis of the disease. (bmj.com)
  • The genetic basis of normopepsinogenemic I duodenal ulcer was also shown by the familial aggregation of this disorder. (annals.org)
  • Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. (oup.com)
  • Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. (oup.com)
  • They also indicate that sporadic and familial MS share a common genetic susceptibility. (oup.com)
  • Mulcahy, G. M. / Genetic heterogeneity and familial carcinoma of the breast . (elsevier.com)
  • 8 Analyses of five additional families reported here demonstrate that the same genetic locus causes Holt-Oram syndrome in more than 60 affected individuals. (ahajournals.org)
  • Additionally, linkage analyses have suggested a modicum of genetic heterogeneity, with the majority of PJS families showing linkage to the LKB1 locus. (nih.gov)
  • Locus heterogeneity characterizes a variety of skeletal dysplasias often due to interacting or overlapping signaling pathways. (nih.gov)
  • Locus heterogeneity poses a challenge for QTL mapping. (biomedcentral.com)
  • Despite drastically increased evidence of multiple levels of heterogeneity in cancer, the general approach has been to eliminate the "noise" of heterogeneity to establish genetic and epigenetic patterns. (nih.gov)
  • Although the autoimmune destruction of β-cells has a major role in the development of type 1 diabetes, there is growing evidence that the differences in clinical, metabolic, immunologic, and genetic characteristics among patients ( 1 ) likely reflect diverse etiology and pathogenesis ( 2 ). (diabetesjournals.org)
  • These data provide direct evidence for genetic heterogeneity of duodenal ulcer disease. (annals.org)
  • Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has. (oup.com)
  • To date, published linkage studies have provided no evidence of genetic heterogeneity in severe neonatal myotubular myopathy (XLMTM). (mysciencework.com)
  • We test for linkage, accounting for heterogeneity, and classify individual families as "linked" and "unlinked" on the basis of their contribution to the overall evidence of linkage. (biomedcentral.com)
  • Here, we use a statistical model that accounts for heterogeneity and apply our method to follow up linkage evidence of trans regulators of gene expression. (biomedcentral.com)
  • Our results provide direct evidence that immune pressure shapes the level of intratumor genetic heterogeneity and have important implications for the design of therapeutic strategies. (sciencemag.org)
  • Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic heterogeneity in detail. (nii.ac.jp)
  • Methods : Using a newly developed massive-parallel ultra-deep sequencing technique, we investigated the viral genetic heterogeneity in 27 chronic hepatitis C patients receiving peg-interferon (IFN) α2b plus ribavirin therapy. (nii.ac.jp)
  • Therefore, we conclude that benign colon lesions display extensive genetic heterogeneity, that they are not prone to release DNA into the circulation and are unlikely to be reliably detected with liquid biopsies, at least with the current technologies. (le.ac.uk)
  • The degree of inter- and intratumor genetic heterogeneity has not yet been defined. (semanticscholar.org)
  • Iceland has been said to be an "island so inbred that it is a happy genetic hunting ground", ideal for gene mapping, and that "nowhere else has such a pure - and predictable - genetic inheritance" in the popular press. (innovations-report.com)
  • Cystic fibrosis is an inherited autosomal recessive genetic disorder that occurs through a mutation in a single gene that codes for the cystic fibrosis transmembrane conductance regulator. (wikipedia.org)
  • Disorders on the Autism spectrum have high levels of genetic heterogeneity and result from multiple genetic pathways including single gene mutation disorders (such as Fragile X Syndrome), regional and submicroscopic variations in the number of gene copies (either heritable or de novo), rare and common genetic variants, and chromosomal aberrations. (wikipedia.org)
  • The analysis of the relationship between gene, epigenetic and genome level heterogeneity, and the challenges of measuring heterogeneity among multiple levels have been discussed. (nih.gov)
  • This includes an introduction to the relationship between epistatic gene action, statistical epistasis, and genetic variance heterogeneity, and a brief discussion about how genetic processes other than epistasis can also give rise to genetic variance heterogeneity. (diva-portal.org)
  • Finally, this study stresses the importance of understanding intra-colonial dispersal and genetic mixing mechanisms in order to better estimate species-wide gene flows and population dynamics. (uio.no)
  • The analysis of the nucleotide sequence of the COI mitochondrial gene fragment and internal transcribed nuclear DNA spacer (ITS1) demonstrates that the studied gastropods are represented in Lake Baikal by three genetic groups. (deepdyve.com)
  • Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. (elsevier.com)
  • Genetic heterogeneity for amplification of HER2 gene status in invasive breast cancer is defined and guidelines established for assessing and reporting HER2 results in these cases. (elsevier.com)
  • Comprehensive reverse genetic resources, which have been key to understanding gene function in diploid model organisms, are missing in many polyploid crops. (pnas.org)
  • One of the tests used to diagnose type 2 diabetes and monitor blood sugar control is influenced by 60 genetic variants, an international team of scientists, including those from the Wellcome Trust Sanger Institute, has found. (medicalxpress.com)
  • The genetic findings included novel variants in ANO10 , CACNA1A , PRKCG and SPG7 . (springer.com)
  • For traits with complex genetic inheritance it has generally proven very difficult to identify the majority of the specific causative variants involved. (prolekare.cz)
  • Here, we define the genetic variants associated with PSIS followed by the same pediatric endocrinologist. (cdc.gov)
  • The resulting genetic heterogeneity contributes to the emergence of variants that may ultimately display increased resistance to immune effector mechanisms and enhanced metastatic potential. (sciencemag.org)
  • Genetic testing identified 22 variants in BEST1. (ox.ac.uk)
  • Previous large-scale sequencing studies have concluded that the extensive inter- and intratumoral genetic heterogeneity observed in melanoma reflects one of the highest mutational loads in all cancers ( 4, 5, 8-13 ). (aacrjournals.org)
  • Paired primary breast cancers and metachronous metastases after adjuvant treatment are reported to differ in their clonal composition and genetic alterations, but it is unclear whether these differences stem from the selective pressures of the metastatic process, the systemic therapies, or both. (aacrjournals.org)
  • Recently, circulating cell-free DNA (cfDNA) has received much attention as a cancer biomarker for its ability to monitor the progression of advanced disease, predict tumor recurrence and reflect the complex genetic heterogeneity of cancers. (le.ac.uk)
  • This study showed beyond doubt that this "catch-all" diagnosis of exclusion in fact refers to a group of cancers that exhibit great genetic heterogeneity. (biomedcentral.com)
  • An analysis of genetic heterogeneity in untreated cancers. (cdc.gov)
  • Here, we review the different forms of genetic heterogeneity in cancer and re-analyse the extent of genetic heterogeneity within seven types of untreated epithelial cancers, with particular regard to its clinical relevance. (cdc.gov)
  • Genetic and epigenetic heterogeneity (the main form of non-genetic heterogeneity) are key elements in cancer progression and drug resistance, as they provide needed population diversity, complexity, and robustness. (nih.gov)
  • Through IL-33 administration and Treg-specific genetic ablation of ST2 we find that IL-33 signaling may be necessary and sufficient for increased numbers of terminally-differentiated effector Tregs during tumor progression. (mit.edu)
  • A reduced accuracy in DNA replication during tumor progression leads to marked heterogeneity of malignant cells and therapeutic resistance [ 2 ]. (omicsonline.org)
  • The combination of an expansion of tumor subclones with varying genetic and genomic alterations and the interaction between the tumor cells and the tumor microenvironment (TME), for example, malignant, stromal, and immune cells, during cancer progression presents an intricate situation that influences disease development ( 6-8 ). (aacrjournals.org)
  • Clinically, the genetic diversity of the tumor in relation to that of the TME may be an important factor in explaining tumor progression, response to treatments, emergence of therapy resistance, and outcome differences in melanoma. (aacrjournals.org)
  • The purpose of this thesis was to obtain some insight into the role of genetic changes in progression of human colorectal cancer. (gla.ac.uk)
  • The genetic changes that drive disease progression can then be identified by the locations of transposon insertions [2-9]. (acmbcb.org)
  • CTCs can serve as a "liquid biopsy", allowing researchers to study genetic progression in real time. (wordpress.com)
  • unpublished work) that accounts for heterogeneity with respect to linkage. (biomedcentral.com)
  • The main theme of the work was the use of paired tumour samples from the same patients in an attempt to measure the extent of genetic heterogeneity and clonal diversity between primary tumours and their synchronous metastases. (gla.ac.uk)
  • Within the first scenario implants are supposed to be of heterogeneous origin and thus comprise a different genetic pattern as compared to the ovarian tumor while metastases are postulated to rise in a clonal manner and thus should closely mimic their primary. (biomedcentral.com)
  • Landscape structure and hierarchical genetic diversity in the brook charr, Salvelinus fontinalis . (springer.com)
  • How genetic diversity is maintained in philopatric colonial systems remains unclear, and understanding the dynamic balance of philopatry and dispersal at all spatial scales is essential to the study of the evolution of coloniality. (uio.no)
  • We found that despite strong natal and breeding site fidelity, king penguins retain a high degree of panmixia and genetic diversity. (uio.no)
  • The causes of cognitive diversity are unclear, however exploration of the genetic contribution to cognitive profiles is unearthing promising developments. (edu.au)
  • To address these questions, we introduced a multicolor barcoding strategy to study the growth of a MYC-driven B cell lymphoma harboring a large degree of intratumor genetic diversity. (sciencemag.org)
  • The paper I'm reviewing today, "Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines" by Powell et al. (wordpress.com)
  • Genetic heterogeneity occurs through the production of single or similar phenotypes through different genetic mechanisms. (wikipedia.org)
  • Increased understanding of the role of genetic heterogeneity and the mechanisms through which it produces common disease phenotypes will facilitate the development of effective prevention and treatment methods for these diseases. (wikipedia.org)
  • To investigate this missing heritability, we recruited 21 families with at least one family member clinically diagnosed with Robinow or Robinow-like phenotypes and performed genetic and genomic studies. (nih.gov)
  • Uncovering the genetic basis of quantitative phenotypes is a central, yet unresolved problem in biology. (prolekare.cz)
  • Those organisms with the greatest genetic resources and with a community of researchers focused on a single system provide a logical starting point toward finding the missing heritability associated with quantitative phenotypes. (prolekare.cz)
  • Even patients with subtle phenotypes exhibit this, suggesting that the underlying genetic defect prevents normal induction of developing vasculature. (bmj.com)
  • Here, we analyze selected expression phenotypes from the Genetic Analysis Workshop 15 (GAW15) Problem 1 data. (biomedcentral.com)
  • Results : Ultra-deep sequencing determined a total of more than 10 million nucleotides of the HCV genome, corresponding to a mean of more than 1000 clones in each specimen, and unveiled extremely high genetic heterogeneity in the genotype 1b HCV population. (nii.ac.jp)
  • The present study narrates a comprehensive genomic analysis of cosmopolitan genotype and presents notable genetic characteristics that occurred during its evolution and global expansion. (nature.com)
  • Based on current understanding, we hypothesized that DENV-2 cosmopolitan genotype has evolved in parallel to its global dispersal to achieve a higher heterogeneity than other DENV-2 genotypes. (nature.com)
  • The current study, therefore, investigated the evolutionary characteristics and global dispersal patterns of DENV-2 cosmopolitan genotype to decipher genetic heterogeneity, distinctness and geographical dominance. (nature.com)
  • The spatial genetic structuring of the land snail Helix aspersa was investigated for 32 colonies within an intensive agricultural area, the polders of the Bay of Mont-Saint-Michel (France). (springer.com)
  • To evaluate the distance as well as the direction over which the spatial genetic arrangement occurs, two-dimensional spatial autocorrelation analyses, Mantel tests of association and multivariate Mantel correlograms were used. (springer.com)
  • Genetic distances based only on genetic drift yielded the most plausible biologically meaningful interpretation of the observed spatial structure. (springer.com)
  • Our results also emphasize the importance of sampling design for estimation of population parameters in colonial seabirds, as at high spatial resolution, basic genetic features are shown to be location-dependent. (uio.no)
  • This study analysed the genetic structure of Styela plicata, a solitary ascidian introduced in harbours and marinas of tropical and temperate waters, across spatial and temporal scales. (csic.es)
  • Our results revealed spatial structure and temporal genetic homogeneity in S. plicata, suggesting a limited role of recurrent, vessel-mediated transport of organisms among small to medium-size harbours. (csic.es)
  • A three and one-half year study of spatial and temporal genetic heterogeneity in a population of the cyclically, parthenogenetic cladoceran, Daphnia pulex, inhabiting a permanent farm pond in east-central Illinois, indicated that electrophoretically distinct genotypes (clones) are frequently distributed non-randomly in the pond, both vertically and horizontally. (illinois.edu)
  • Furthermore, HGSOC is characterized by extensive genomic heterogeneity, and the impact of this heterogeneity on the immune microenviroment is currently unknown. (sciencemag.org)
  • The analysis of our results indicates genomic heterogeneity in the clinical isolates. (biomedcentral.com)
  • The etiological heterogeneity of idiopathic diabetes has been recognized for 25 years, and subdivision into type 1 and type 2 diabetes is fundamental to the way we think about the disease. (diabetesjournals.org)
  • Recent tumor sequencing data suggest an urgent need to develop a methodology to directly address intratumoral heterogeneity in the design of anticancer treatment regimens. (aacrjournals.org)
  • This study demonstrates the presence of genetic heterogeneity in colorectal adenomas and supports the notion that K-ras mutation is an early event, while aneuploidy is a late event in the adenoma-carcinoma sequence. (nih.gov)
  • Mutation analysis revealed genetic alterations in LKB1 in two probands who had a family history of PJS. (nih.gov)
  • The key attribute of marked heterogeneity in genomic lesions attests for the essential evolution of the mutator phenotype per se, and allows for the emergence of oncogenesis beyond initial or middle course events in malignant transformation. (omicsonline.org)
  • Cutaneous malignant melanoma (melanoma) is characterized by a high mutational load, extensive intertumoral and intratumoral genetic heterogeneity, and complex tumor microenvironment (TME) interactions. (aacrjournals.org)
  • Tumor genetic heterogeneity has emerged as an effective biomarker of malignant processes 1-4 . (wordpress.com)
  • Patients with genetic lesions in the Type-1 cytokine/cytokine receptor pathway exhibit a selective susceptibility to severe infections with poorly pathogenic mycobacteria and non-typhi salmonella spp. (lshtm.ac.uk)
  • Further, we propose that measuring genome level heterogeneity represents an effective strategy in the study of cancer and other types of complex diseases, as emphasis on the pattern of system evolution rather than specific pathways provides a global and synthetic approach. (nih.gov)
  • The progressive decline of genetic similarity with physical distance appeared to be environmentally induced, leading to functional migration pathways. (springer.com)
  • On the basis of the data obtained and geological and climatic history of Baikal, possible pathways of the B. fragilis resettlement in the lake and the emergence of three genetic groups are hypothesized. (deepdyve.com)
  • Over the past decade, considerable progress has been made in the identification of genetic risk factors for ASD that define specific mechanisms and pathways underlying the associated behavioural deficits. (escholarship.org)
  • Epistasis and genetic variance heterogeneity are two non-additive genetic inheritance patterns that are often, but not always, related. (diva-portal.org)
  • Factors that govern this heterogeneity are poorly understood, yet these may have important implications for prognosis, therapy, and prevention. (diabetesjournals.org)
  • Conclusion : Use of the ultra-deep sequencing technology revealed massive genetic heterogeneity of HCV, which has important implications regarding the treatment response and outcome of antiviral therapy. (nii.ac.jp)
  • We also present current clinical guidelines for genetic testing in ASD and their implications for prognosis and treatment. (escholarship.org)
  • Tumourigenesis is generally considered a multistep process in which multiple genetic alterations occur, eventually reflected in abnormalities of the cellular DNA content. (nih.gov)
  • To date, the majority of individuals with PJS have been found to have genetic alterations in LKB1, most of which result in protein truncation. (nih.gov)
  • We sought to define the repertoire of genetic alterations in breast cancer patients with de novo metastatic disease who had not received local or systemic therapy. (aacrjournals.org)
  • Genetic heterogeneity in sporadic colorectal adenomas. (nih.gov)
  • Leicester Research Archive: Circulating tumor DNA in patients with colorectal adenomas: assessment of detectability and genetic heterogeneity. (le.ac.uk)
  • these features are likely to induce heterogeneity of marker effects across subpopulations. (genetics.org)
  • The estimated genomic correlations between subpopulations varied from null to moderate, depending on the genetic distance between subpopulations and traits. (genetics.org)
  • To account for heterogeneity of marker effects across subpopulations, they can simply be estimated within each population separately. (genetics.org)
  • Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer. (hindawi.com)
  • This points towards heterogeneous population structure at the sub-colony level, in which fine-scale environmental features drive local philopatric behaviour, while lower-quality patches may act as genetic mixing mechanisms at the colony level. (uio.no)
  • This high prevalence, combined with the striking genetic heterogeneity of deafness, has made this Mendelian disease a major challenge in terms of discovering its cause and deciphering the mechanisms underlying it. (biomedcentral.com)
  • and (d) current understanding of epigenetic mechanisms whereby environmental events may alter behavioral expression of genetic variations. (frontiersin.org)
  • While its etiology is not well understood, genetic factors are clearly involved. (oup.com)
  • In this report we describe the clinical and genetic evaluation of a four generational German RDP family with eight definitely affected and one possibly affected members. (bmj.com)
  • Association of Clinical and Genetic Heterogeneity With BEST1 Sequence Variations. (ox.ac.uk)
  • Professor Árnason explains in his article: "Recently, statements have been made about a special 'genetic homogeneity' of the Icelanders that are at variance with earlier work on blood groups and allozymes. (innovations-report.com)
  • On the relationship between epistasis and genetic variance heterogeneity. (diva-portal.org)
  • Spatiotemporal Heterogeneity Characterizes the Genetic Landscape of Pheochromocytoma and Defines Early Events in Tumorigenesis. (semanticscholar.org)
  • article{Crona2015SpatiotemporalHC, title={Spatiotemporal Heterogeneity Characterizes the Genetic Landscape of Pheochromocytoma and Defines Early Events in Tumorigenesis. (semanticscholar.org)
  • When a cancer cell divides, both daughter cells inherit the genetic and epigenetic abnormalities of the parent cell, and may also acquire new genetic and epigenetic abnormalities in the process of cellular reproduction. (wikipedia.org)
  • While many of the genetic and epigenetic abnormalities in neoplasms are probably neutral evolution , many have been shown to increase the proliferation of the mutant cells, or decrease their rate of death ( apoptosis ). (wikipedia.org)
  • Despite multiple similarities in the clinical presentations of these syndromes, it remains unknown whether hereditary heart-hand syndromes arise from common or distinct genetic defects. (ahajournals.org)
  • Cloning, sequencing, and phylogenetic comparisons of these amplified 140-bp pol fragments indicated that there are at least two distinct genetic substrains of HTLV-II in the Western Hemisphere. (asm.org)
  • Left ventricular non-compaction revisited: a distinct phenotype with genetic heterogeneity? (uzh.ch)
  • Cousins not twins: intratumoural and intertumoural heterogeneity in syndromic neuroendocrine tumours. (semanticscholar.org)
  • Genetic intratumoural heterogeneity is a natural consequence of imperfect DNA replication. (cdc.gov)
  • Marked genetic heterogeneity is correlated to multiple levels of causation in many common human diseases including cystic fibrosis, Alzheimer's disease, autism spectrum disorders, inherited predisposition to breast cancer, and non-syndromic hearing loss. (wikipedia.org)
  • Genetic and epigenetic heterogeneity in cancer: a genome-centric perspective. (nih.gov)
  • In particular, the appreciation of new types of epigenetic regulation like non-coding RNA, have led to the hope of solving the mystery of cancer that the current genetic theories seem to be unable to achieve. (nih.gov)
  • In this mini-review, we have briefly analyzed a number of mis-conceptions regarding cancer heterogeneity, followed by the re-evaluation of cancer heterogeneity within a framework of the genome-centric concept of evolution. (nih.gov)
  • The genetic complexity and heterogeneity of cancer has posed a problem in designing rationally targeted therapies effective in a large proportion of human cancer. (acmbcb.org)
  • Genetic heterogeneity in breast cancer: the road to personalized medicine? (biomedcentral.com)
  • Hammond, M. Elizabeth H. / Genetic heterogeneity in HER2 testing in breast cancer panel summary and guidelines . (elsevier.com)
  • Auerbach, Arleen D. / Genetic heterogeneity among fanconi anemia heterozygotes and risk of cancer . (elsevier.com)
  • Taken with its companion volumes, Stem Cells Heterogeneity: Novel Concepts and Stem Cells Heterogeneity in Cancer , this book is essential reading for advanced cell biology students as well as researchers and clinicians working with stem cells. (exlibris.ch)
  • Moreover, greater heterogeneity is associated with worse outcomes for several types of cancer. (bcr.org)
  • likely reflecting heterogeneity of the disease in different genetic backgrounds. (wikipedia.org)
  • Population screening strategies based on detection of occult blood in the feces have contributed to enhance detection rates of localized disease, but new approaches based on genetic analyses able to increase specificity and sensitivity could provide additional advantages compared to current screening methodologies. (le.ac.uk)
  • Neoplasms are mosaics of different mutant cells with both genetic and epigenetic changes that distinguish them from normal cells. (wikipedia.org)
  • These results support the hypothesis that the aetiology of ICP is heterogeneous and that ICP is due to a genetic predisposition in a proportion of patients. (bmj.com)
  • Background and Aims : The hepatitis C virus (HCV) invariably shows wide heterogeneity in infected patients, referred to as a quasispecies population. (nii.ac.jp)
  • The heterogeneity of the disease is clearly demonstrated by patients diagnosed with stage III melanoma, which is a group characterized by a high risk of relapse and 5-year relative survival rates between 40% and 70% ( 14 ). (aacrjournals.org)
  • In a search for a genetic marker of duodenal ulcer, we measured serum pepsinogen I levels in 168 ulcer patients and 151 of their clinically normal siblings. (annals.org)
  • Since both KRAS and BRAF are known to be frequently mutated in s-BOTs [ 11 ], they are especially suitable to indicate a possible genetic descent of extraovarian implants in s-BOT patients. (biomedcentral.com)
  • PURPOSE Pheochromocytoma and paraganglioma (PPGL) patients display heterogeneity in the clinical presentation and underlying genetic cause. (semanticscholar.org)
  • Analysis of genetic heterogeneity of hepatitis C viruses in Central America reveals a novel. (deepdyve.com)
  • The current study reveals genetic heterogeneity of s-BOTs and implants, as none of the markers examined showed constant reciprocity. (biomedcentral.com)
  • This study aims to develop droplet-based microfluidics for massively parallel single-cell genomics, to elucidate intra-tissue genetic heterogeneity at the single-cell resolution. (go.jp)
  • Here, we present the first fine-scale study of the genetic structure in a king penguin colony in the Crozet Archipelago. (uio.no)
  • Leicester Research Archive: A study of genetic heterogeneity in Albright hereditary osteodystrophy. (le.ac.uk)
  • Study of the genetic heterogeneity of SAT-2 foot-and-mouth disease virus in sub-Saharan Africa with specific focus on East Africa. (semanticscholar.org)
  • The aim of this study was to explore the contribution of histological, serological, and genetic factors to disease presentation. (ox.ac.uk)
  • The study concluded that these repeats were absent in pathologically confirmed MSA, suggesting an alternative genetic cause. (wikipedia.org)
  • These findings show how a lack of global genetic structuring can emerge from small-scale heterogeneity in ecological parameters, as opposed to the classical model of homogeneous dispersal. (uio.no)
  • Our findings suggest the primary mechanism for elevated androgen levels in PCOS may differ between non-obese and obese women with PCOS and that the clinical heterogeneity seen in PCOS may have genetic underpinnings. (prolekare.cz)
  • Disentangling the heterogeneity of autism spectrum disorder through genetic findings. (escholarship.org)
  • Our findings strongly suggest genetic heterogeneity in myotubular myopathy and indicate that great care should be taken when using Xq28 markers in linkage studies for prenatal diagnosis and genetic counseling. (mysciencework.com)
  • Our studies in two separate cohorts have shown that the type 2 diabetes-associated TCF7L2 genetic variant is more frequent among specific subsets of individuals with autoimmune type 1 diabetes, specifically those with fewer markers of islet autoimmunity ( 22 , 23 ). (diabetesjournals.org)
  • Usage information: Genetic heterogeneity in the cerebrohepatorenal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions. (jci.org)