Genetic Heterogeneity: The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Genetic Linkage: The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.Lod Score: The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds."Genetic Variation: Genotypic differences observed among individuals in a population.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.Genes, Recessive: Genes that influence the PHENOTYPE only in the homozygous state.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Consanguinity: The magnitude of INBREEDING in humans.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Chromosomes, Human, Pair 2: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Exome: That part of the genome that corresponds to the complete complement of EXONS of an organism or cell.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX.Syndrome: A characteristic symptom complex.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Chromosomes, Human, Pair 19: A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Homozygote: An individual in which both alleles at a given locus are identical.Penetrance: 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)Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Chromosomes, Human, Pair 1: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Family Health: 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.Genetic Diseases, Inborn: Diseases that are caused by genetic mutations present during embryo or fetal development, although they may be observed later in life. The mutations may be inherited from a parent's genome or they may be acquired in utero.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Ichthyosis: 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.Chromosomes, Human, Pair 16: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Chromosomes, Human, Pair 3: A specific pair of human chromosomes in group A (CHROMOSOMES, HUMAN, 1-3) of the human chromosome classification.Polymorphism, Restriction Fragment Length: Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.Chromosomes, Human, Pair 5: One of the two pairs of human chromosomes in the group B class (CHROMOSOMES, HUMAN, 4-5).Age of Onset: 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.Founder Effect: 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.Chromosomes, Human, Pair 17: A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.Chromosomes, Human, Pair 6: A specific pair GROUP C CHROMSOMES of the human chromosome classification.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Abnormalities, MultiplePolymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Bardet-Biedl Syndrome: 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)Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Multifactor Dimensionality Reduction: A statistical tool for detecting and modeling gene-gene interactions. It is a non-parametric and model-free approach.Encephalocele: 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.Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.Genome-Wide Association Study: An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.Chromosomes, Human, Pair 9: A specific pair of GROUP C CHROMSOMES of the human chromosome classification.Chromosomes, Human, Pair 7: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Chromosomes, Human, Pair 12: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Family: A social group consisting of parents or parent substitutes and children.Chromosomes, Human, Pair 10: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Chromosomes, Human, Pair 11: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).X Chromosome: 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.Deafness: A general term for the complete loss of the ability to hear from both ears.Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with well-defined distribution patterns in relation to time or place or both.Indians, South American: Individual members of South American ethnic groups with historic ancestral origins in Asia.Chromosomes, Human, Pair 8: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Microcephaly: 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.)Genetic Association Studies: The analysis of a sequence such as a region of a chromosome, a haplotype, a gene, or an allele for its involvement in controlling the phenotype of a specific trait, metabolic pathway, or disease.Glycosuria, Renal: 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.Leiomyoma, Epithelioid: 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)Hereditary Sensory and Motor Neuropathy: 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)Genetics, Population: The discipline studying genetic composition of populations and effects of factors such as GENETIC SELECTION, population size, MUTATION, migration, and GENETIC DRIFT on the frequencies of various GENOTYPES and PHENOTYPES using a variety of GENETIC TECHNIQUES.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.Jews: An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.Hyperkeratosis, Epidermolytic: 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.Heterozygote Detection: Identification of genetic carriers for a given trait.Chromosomes, Human, Pair 22: A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.Epistasis, Genetic: A form of gene interaction whereby the expression of one gene interferes with or masks the expression of a different gene or genes. Genes whose expression interferes with or masks the effects of other genes are said to be epistatic to the effected genes. Genes whose expression is affected (blocked or masked) are hypostatic to the interfering genes.Osteochondrodysplasias: Abnormal development of cartilage and bone.ItalyChromosomes, Human, Pair 15: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Rubinstein-Taybi Syndrome: 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).Chromosomes, Human, Pair 4: A specific pair of GROUP B CHROMOSOMES of the human chromosome classification.Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone.Polymorphism, Single-Stranded Conformational: 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.Cystinuria: 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, Starch Gel: Electrophoresis in which a starch gel (a mixture of amylose and amylopectin) is used as the diffusion medium.DNA Fingerprinting: A technique for identifying individuals of a species that is based on the uniqueness of their DNA sequence. Uniqueness is determined by identifying which combination of allelic variations occur in the individual at a statistically relevant number of different loci. In forensic studies, RESTRICTION FRAGMENT LENGTH POLYMORPHISM of multiple, highly polymorphic VNTR LOCI or MICROSATELLITE REPEAT loci are analyzed. The number of loci used for the profile depends on the ALLELE FREQUENCY in the population.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Eye Abnormalities: Congenital absence of or defects in structures of the eye; may also be hereditary.In Situ Hybridization, Fluorescence: 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.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Chromosomes, Human: 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.Optic Atrophies, Hereditary: 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).Intellectual Disability: 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)Ectodermal Dysplasia: 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.Frameshift Mutation: 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.Gaucher Disease: 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.Group II Chaperonins: 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.Glucosidases: Enzymes that hydrolyze O-glucosyl-compounds. (Enzyme Nomenclature, 1992) EC 3.2.1.-.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Loss of Heterozygosity: 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.Spastic Paraplegia, Hereditary: 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)Point Mutation: 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.Polydactyly: A congenital anomaly of the hand or foot, marked by the presence of supernumerary digits.Chromosomes, Human, Pair 20: A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Infant, Newborn: An infant during the first month after birth.Familial Mediterranean Fever: 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.Muscular Dystrophies: 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.Glycogen Storage Disease: 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.Dysplastic Nevus Syndrome: 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)Eye Diseases, Hereditary: 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.DNA, Mitochondrial: Double-stranded DNA of MITOCHONDRIA. In eukaryotes, the mitochondrial GENOME is circular and codes for ribosomal RNAs, transfer RNAs, and about 10 proteins.DNA Probes: 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.Refsum Disease: 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.France: 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.Mutation Rate: The number of mutations that occur in a specific sequence, GENE, or GENOME over a specified period of time such as years, CELL DIVISIONS, or generations.Usher Syndromes: 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.Karyotyping: Mapping of the KARYOTYPE of a cell.Hearing Loss, Sensorineural: 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.Glucosylceramidase: 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 Amplified Polymorphic DNA Technique: Technique that utilizes low-stringency polymerase chain reaction (PCR) amplification with single primers of arbitrary sequence to generate strain-specific arrays of anonymous DNA fragments. RAPD technique may be used to determine taxonomic identity, assess kinship relationships, analyze mixed genome samples, and create specific probes.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.Codon, Nonsense: 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.Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.DNA Copy Number Variations: Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.Blotting, Southern: 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, Neoplasm: DNA present in neoplastic tissue.Bacterial Typing Techniques: 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.Membrane Proteins: 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.Inheritance Patterns: The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION.Models, Statistical: Statistical formulations or analyses which, when applied to data and found to fit the data, are then used to verify the assumptions and parameters used in the analysis. Examples of statistical models are the linear model, binomial model, polynomial model, two-parameter model, etc.Chromosomes, Human, Pair 13: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Molecular Epidemiology: 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.Malignant Hyperthermia: Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia.Neoplastic Syndromes, Hereditary: 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.European Continental Ancestry Group: Individuals whose ancestral origins are in the continent of Europe.Spain: Parliamentary democracy located between France on the northeast and Portugual on the west and bordered by the Atlantic Ocean and the Mediterranean Sea.DNA, Ribosomal: DNA sequences encoding RIBOSOMAL RNA and the segments of DNA separating the individual ribosomal RNA genes, referred to as RIBOSOMAL SPACER DNA.Hearing Loss: A general term for the complete or partial loss of the ability to hear from one or both ears.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Electrophoresis, Gel, Pulsed-Field: 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.High-Throughput Nucleotide Sequencing: Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc.Serotyping: Process of determining and distinguishing species of bacteria or viruses based on antigens they share.Cerebellar Ataxia: 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)Clone Cells: 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)Chromosomes, Human, Pair 14: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.Genetic Loci: Specific regions that are mapped within a GENOME. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of CHROMOSOME 6. Many well known genetic loci are also known by common names that are associated with a genetic function or HEREDITARY DISEASE.Chromosome Deletion: Actual loss of portion of a chromosome.Comparative Genomic Hybridization: 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.Tuberous Sclerosis: 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.Siblings: Persons or animals having at least one parent in common. (American College Dictionary, 3d ed)Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Muscular Diseases: Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.Charcot-Marie-Tooth Disease: 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)Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Oligonucleotide Array Sequence Analysis: Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.Retinal DiseasesConnexins: 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.Disease Susceptibility: 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.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.Nuclear Family: A family composed of spouses and their children.Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.HLA Antigens: 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.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Molecular Biology: A discipline concerned with studying biological phenomena in terms of the chemical and physical interactions of molecules.Proteins: 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)

  • 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 ]. (
  • Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes. (
  • 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. (
  • This potential genetic heterogeneity displayed by cell lines cultured in vitro has led to certain opposition to the use of cancer cell lines in modern drug testing ( 1 , 2 ). (
  • The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist. (
  • Furthermore, massive parallel sequencing of RPMI‑8402 provided insight into the evolution of T‑ALL carcinogenesis, since this cell line exhibited the genetic heterogeneity typical of T‑ALL. (
  • Hammond, M. Elizabeth H. / Genetic heterogeneity in HER2 testing in breast cancer panel summary and guidelines . (
  • 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. (
  • 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. (
  • The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. (
  • 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. (
  • Genetic heterogeneity in pbp genes among clinically isolated group B Streptococci with reduced penicillin susceptibility. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • This unusual finding may represent genetic heterogeneity, germinal mutation of an autosomal dominant gene, and an epistatic recessive gene that suppressed the expression of the abnormal gene in the father, his parents being first cousins. (
  • 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. (
  • 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. (
  • Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes. (
  • For molecular genetic analysis, 16 individuals from two independently ascertained Finnish ICP families were genotyped for the flanking markers for BSEP , FIC1 , and MDR3 . (
  • Molecular genetic analysis also excluded linkage to the DYT6 locus and the GAG deletion in DYT1 , suggesting at least one additional RDP gene. (
  • 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. (
  • 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. (
  • 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. (
  • Massive amounts of genetic information due to the abundance of HCV variants could be an obstacle to evaluate the viral genetic heterogeneity in detail. (
  • 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. (
  • 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. (
  • Autosomal recessive primary microcephaly (MCPH) is a rare and heterogeneous genetic disorder characterized by reduced head circumference, low cognitive prowess and, in general, architecturally normal brains. (
  • Nagwa Abdel Meguid Mohamed , Genetic heterogeneity of isolated microcephaly, New Egypt. (
  • 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. (
  • 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. (
  • 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. (
  • Moreover, greater heterogeneity is associated with worse outcomes for several types of cancer. (
  • Genetic heterogeneity occurs through the production of single of similar phenotypes through different genetic mechanisms. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • and (d) current understanding of epigenetic mechanisms whereby environmental events may alter behavioral expression of genetic variations. (
  • 7 The present paper reports on the clinical and genetic features in 11 black African families and briefly reviews the literature on HD in blacks in Africa. (
  • 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. (
  • Yet, genetic structure appears markedly heterogeneous across the colony, with higher-than-expected inbreeding levels, and local inbreeding and relatedness hotspots that overlap predicted higher-quality nesting locations. (
  • 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. (
  • 2008) The genetic legacy of religious diversity and intolerance: paternal lineages of Christians, Jews, and Muslims in the Iberian Peninsula. (
  • We found that despite strong natal and breeding site fidelity, king penguins retain a high degree of panmixia and genetic diversity. (
  • The causes of cognitive diversity are unclear, however exploration of the genetic contribution to cognitive profiles is unearthing promising developments. (
  • This complex genetic population structure should be taken into account when designing biomedical approaches in North African groups. (
  • 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. (
  • 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. (
  • 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. (
  • Tumourigenesis is generally considered a multistep process in which multiple genetic alterations occur, eventually reflected in abnormalities of the cellular DNA content. (
  • 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. (
  • 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 ). (
  • In fact, the heterogeneity among HTLV-II strains from the Western Hemisphere was similar to that observed in HTLV-I and simian T-cell lymphoma/leukemia virus type I isolates from around the world, including Japan, Africa, and Papua New Guinea. (
  • The phylogenetic analysis revealed the existence of type 1 strains of a novel genetic lineage, recently described for some South American countries, and indicates an increasing diversification of HCV. (
  • Neoplasms are mosaics of different mutant cells with both genetic and epigenetic changes that distinguish them from normal cells. (
  • 2000) Genetic structure of north‐west Africa revealed by STR analysis. (
  • 4 ). For that analysis, we combined the data into a single sample and used a single linkage map constructed from the deCODE high-density map, Marshfield genetic maps, and the UCSC Genome Browser to validate the relative order of markers, and performed multipoint MLS analysis under the possible triangle (i.e. (
  • We have used complementation analysis after somatic cell fusion to investigate the genetic relationships among various genetic diseases in humans in which there is a simultaneous impairment of several peroxisomal functions. (
  • Short report: genetic heterogeneity of Japanese encephalitis virus assessed via analysis of the full-length genome sequence of a Korean isolate. (
  • Components addressed included a definition of HER2 amplification heterogeneity, practice guidelines for examination of the tissue, and reporting criteria for this analysis. (
  • Here, we analyze selected expression phenotypes from the Genetic Analysis Workshop 15 (GAW15) Problem 1 data. (
  • Genetic testing strategies such as next-generation sequencing (NGS) panels and whole genome sequencing (WGS) can be applied to the hereditary cerebellar ataxias (HCAs), but their exact role in the diagnostic pathway is unclear. (
  • Leicester Research Archive: A study of genetic heterogeneity in Albright hereditary osteodystrophy. (
  • No genetic differences have been found between Arab and Berber groups. (
  • Diel vertical migration surveys demonstrated significant differences in vertical distribution and vertical migration activity among genotypes, strongly suggesting a genetic component to vertical migration, and implying that genetically determined habitat selection exists in this population. (
  • 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. (
  • 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. (