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PenetrancePedigreeGenes, DominantHeterozygoteMutationPhenotypeGenetic LinkageGenetic Predisposition to DiseaseOptic Atrophy, Hereditary, LeberLod ScoreAllelesGerm-Line MutationFamily HealthGenotypeDNA Mutational AnalysisGenetic TestingGenes, BRCA1Genes, ModifierModels, GeneticAge of OnsetFounder EffectHirschsprung DiseaseChromosome MappingHaplotypesHomozygoteGenes, RecessiveJewsGenetic HeterogeneityGene FrequencyGenetic Diseases, InbornGenes, BRCA2Dystonia Musculorum DeformansMutation, MissenseFamilySyndromeGenetic MarkersHeterozygote DetectionCrosses, GeneticDystoniaBRCA2 ProteinAmyloid Neuropathies, FamilialGenetic CounselingGenetic VariationAngiomatosisHemochromatosisPolymorphism, Single NucleotideSyndactylyAbnormalities, MultipleLikelihood FunctionsProto-Oncogene Proteins c-retCraniofacial AbnormalitiesDNA, MitochondrialEpistasis, GeneticRetinoblastomaGenetics, MedicalChromosomes, Human, Pair 19RNA, Transfer, IleCardiomyopathy, Hypertrophic, FamilialBone Morphogenetic Protein Receptors, Type IIPrealbuminMyoclonusNeoplastic Syndromes, HereditaryInheritance PatternsBreast NeoplasmsMice, TransgenicOptic Atrophies, HereditaryExonsDystonic DisordersMice, Inbred C57BLRetinitis PigmentosaParaganglioma, Extra-AdrenalMicrosatellite RepeatsPoint MutationGenetic Association StudiesOvarian NeoplasmsEye Abnormalities
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)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.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Optic Atrophy, Hereditary, Leber: A maternally linked genetic disorder that presents in mid-life as acute or subacute central vision loss leading to central scotoma and blindness. The disease has been associated with missense mutations in the mtDNA, in genes for Complex I, III, and IV polypeptides, that can act autonomously or in association with each other to cause the disease. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim/, MIM#535000 (April 17, 2001))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."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.Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.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.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.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.Genes, BRCA1: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.Genes, Modifier: GENES with ALLELES that affect the PHENOTYPE associated with a nonallelic gene.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.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.Hirschsprung Disease: Congenital MEGACOLON resulting from the absence of ganglion cells (aganglionosis) in a distal segment of the LARGE INTESTINE. The aganglionic segment is permanently contracted thus causing dilatation proximal to it. In most cases, the aganglionic segment is within the RECTUM and SIGMOID COLON.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.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.Homozygote: An individual in which both alleles at a given locus are identical.Genes, Recessive: Genes that influence the PHENOTYPE only in the homozygous state.Jews: An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.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)Gene Frequency: The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.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.Genes, BRCA2: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)Dystonia Musculorum Deformans: A condition characterized by focal DYSTONIA that progresses to involuntary spasmodic contractions of the muscles of the legs, trunk, arms, and face. The hands are often spared, however, sustained axial and limb contractions may lead to a state where the body is grossly contorted. Onset is usually in the first or second decade. Familial patterns of inheritance, primarily autosomal dominant with incomplete penetrance, have been identified. (Adams et al., Principles of Neurology, 6th ed, p1078)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)Family: A social group consisting of parents or parent substitutes and children.Syndrome: A characteristic symptom complex.Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.Heterozygote Detection: Identification of genetic carriers for a given trait.Crosses, Genetic: Deliberate breeding of two different individuals that results in offspring that carry part of the genetic material of each parent. The parent organisms must be genetically compatible and may be from different varieties or closely related species.Dystonia: An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)BRCA2 Protein: A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)Amyloid Neuropathies, Familial: Inherited disorders of the peripheral nervous system associated with the deposition of AMYLOID in nerve tissue. The different clinical types based on symptoms correspond to the presence of a variety of mutations in several different proteins including transthyretin (PREALBUMIN); APOLIPOPROTEIN A-I; and GELSOLIN.Genetic Counseling: An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered.Genetic Variation: Genotypic differences observed among individuals in a population.Angiomatosis: A condition with multiple tumor-like lesions caused either by congenital or developmental malformations of BLOOD VESSELS, or reactive vascular proliferations, such as in bacillary angiomatosis. Angiomatosis is considered non-neoplastic.Hemochromatosis: A disorder of iron metabolism characterized by a triad of HEMOSIDEROSIS; LIVER CIRRHOSIS; and DIABETES MELLITUS. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Syndactyly: A congenital anomaly of the hand or foot, marked by the webbing between adjacent fingers or toes. Syndactylies are classified as complete or incomplete by the degree of joining. Syndactylies can also be simple or complex. Simple syndactyly indicates joining of only skin or soft tissue; complex syndactyly marks joining of bony elements.Abnormalities, MultipleLikelihood 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.Proto-Oncogene Proteins c-ret: Receptor protein-tyrosine kinases involved in the signaling of GLIAL CELL-LINE DERIVED NEUROTROPHIC FACTOR ligands. They contain an extracellular cadherin domain and form a receptor complexes with GDNF RECEPTORS. Mutations in ret protein are responsible for HIRSCHSPRUNG DISEASE and MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones.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.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.Retinoblastoma: A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104)Genetics, Medical: A subdiscipline of human genetics which entails the reliable prediction of certain human disorders as a function of the lineage and/or genetic makeup of an individual or of any two parents or potential parents.Chromosomes, Human, Pair 19: A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.RNA, Transfer, Ile: A transfer RNA which is specific for carrying isoleucine to sites on the ribosomes in preparation for protein synthesis.Cardiomyopathy, Hypertrophic, Familial: An autosomal dominant inherited form of HYPERTROPHIC CARDIOMYOPATHY. It results from any of more than 50 mutations involving genes encoding contractile proteins such as VENTRICULAR MYOSINS; cardiac TROPONIN T; ALPHA-TROPOMYOSIN.Bone Morphogenetic Protein Receptors, Type II: A subtype of bone morphogenetic protein receptors with low affinity for BONE MORPHOGENETIC PROTEINS. They are constitutively active PROTEIN-SERINE-THREONINE KINASES that can interact with and phosphorylate TYPE I BONE MORPHOGENETIC PROTEIN RECEPTORS.Prealbumin: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some CENTRAL NERVOUS SYSTEM DISEASES; (e.g., EPILEPSY, MYOCLONIC). Nocturnal myoclonus is the principal feature of the NOCTURNAL MYOCLONUS SYNDROME. (From Adams et al., Principles of Neurology, 6th ed, pp102-3).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.Inheritance Patterns: The different ways GENES and their ALLELES interact during the transmission of genetic traits that effect the outcome of GENE EXPRESSION.Breast Neoplasms: Tumors or cancer of the human BREAST.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.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).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.Dystonic Disorders: Acquired and inherited conditions that feature DYSTONIA as a primary manifestation of disease. These disorders are generally divided into generalized dystonias (e.g., dystonia musculorum deformans) and focal dystonias (e.g., writer's cramp). They are also classified by patterns of inheritance and by age of onset.Mice, Inbred C57BLRetinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field.Paraganglioma, Extra-Adrenal: A relatively rare, usually benign neoplasm originating in the chemoreceptor tissue of the CAROTID BODY; GLOMUS JUGULARE; GLOMUS TYMPANICUM; AORTIC BODIES; and the female genital tract. It consists histologically of rounded or ovoid hyperchromatic cells that tend to be grouped in an alveolus-like pattern within a scant to moderate amount of fibrous stroma and a few large thin-walled vascular channels. (From Stedman, 27th ed)Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).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.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.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Eye Abnormalities: Congenital absence of or defects in structures of the eye; may also be hereditary.

Evidence that mutations in the X-linked DDP gene cause incompletely penetrant and variable skewed X inactivation. (1/637)

X chromosome inactivation results in the random transcriptional silencing of one of the two X chromosomes early in female development. After random inactivation, certain deleterious X-linked mutations can create a selective disadvantage for cells in which the mutation is on the active X chromosome, leading to X inactivation patterns with the mutation on the inactive X chromosome in nearly 100% of the individual's cells. In contrast to the homogeneous patterns of complete skewed inactivation noted for many X-linked disorders, here we describe a family segregating a mutation in the dystonia-deafness peptide (DDP) gene, in which female carriers show incompletely penetrant and variable X inactivation patterns in peripheral blood leukocytes, ranging between 50:50 and >95:5. To address the genetic basis for the unusual pattern of skewing in this family, we first mapped the locus responsible for the variable skewing to the proximal long arm (Xq12-q22) of the X chromosome (Z=5. 7, P=.002, LOD score 3.57), a region that includes both the DDP and the XIST genes. Examination of multiple cell types from women carrying a DDP mutation and of peripheral blood leukocytes from women from two unrelated families who carry different mutations in the DDP gene suggests that the skewed X inactivation is the result of selection against cells containing the mutant DDP gene on the active X chromosome, although skewing is apparently not as severe as that seen for many other deleterious X-linked mutations. Thus, DDP is an example of an X-linked gene for which mutations cause partial cell selection and thus incompletely skewed X inactivation in peripheral blood leukocytes.  (+info)

Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. (2/637)

Combining data from a genomic screen in 70 families with a high risk for prostate cancer (PC) with data from candidate-region mapping in these families and an additional 71 families, we have localized a potential hereditary PC-susceptibility locus to chromosome 1p36. Because an excess of cases of primary brain cancer (BC) have been observed in some studies of families with a high risk for PC, and because loss of heterozygosity at 1p36 is frequently observed in BC, we further evaluated 12 families with both a history of PC and a blood relative with primary BC. The overall LOD score in these 12 families was 3.22 at a recombination fraction (theta) of .06, with marker D1S507. On the basis of an a priori hypothesis, this group was stratified by age at diagnosis of PC. In the younger age group (mean age at diagnosis <66 years), a maximum two-point LOD score of 3.65 at straight theta = .0 was observed, with D1S407. This linkage was rejected in both early- and late-onset families without a history of BC (LOD scores -7.12 and -6.03, respectively, at straight theta = .0). After exclusion of 3 of the 12 families that had better evidence of linkage to previously described PC-susceptibility loci, linkage to the 1p36 region was suggested by a two-point LOD score of 4.74 at straight theta = .0, with marker D1S407. We conclude that a significant proportion of these families with both a high risk for PC and a family member with BC show linkage to the 1p36 region.  (+info)

Analysis of affected sib pairs, with covariates--with and without constraints. (3/637)

Covariate models have previously been developed as an extension to affected-sib-pair methods in which the covariate effects are jointly estimated with the degree of excess allele sharing. These models can estimate the differences in sib-pair allele sharing that are associated with measurable environment or genes. When there are no covariates, the pattern of identical-by-descent allele sharing in affected sib pairs is expected to fall within a small triangular region of the potential parameter space, under most genetic models. By restriction of the estimated allele sharing to this triangle, improved power is obtained in tests for genetic linkage. When the affected-sib-pair model is generalized to allow for covariates that affect allele sharing, however, new constraints and new methods for the application of constraints are required. Three generalized constraint methods are proposed and evaluated by use of simulated data. The results compare the power of the different methods, with and without covariates, for a single-gene model with age-dependent onset and for quantitative and qualitative gene-environment and gene-gene interaction models. Covariates can improve the power to detect linkage and can be particularly valuable when there are qualitative gene-environment interactions. In most situations, the best strategy is to assume that there is no dominance variance and to obtain constrained estimates for covariate models under this assumption.  (+info)

Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction. (4/637)

The Smads are a family of nine related proteins which function as signaling intermediates for the transforming growth factor beta (TGF-beta) superfamily of ligands. To discern the in vivo functions of one of these Smads, Smad3, we generated mice harboring a targeted disruption of this gene. Smad3 null mice, although smaller than wild-type littermates, are viable, survive to adulthood, and exhibit an early phenotype of forelimb malformation. To study the cellular functions of Smad3, we generated Smad3 null mouse embryonic fibroblasts (MEFs) and dermal fibroblasts. We demonstrate that null MEFs have lost the ability to form Smad-containing DNA binding complexes and are unable to induce transcription from the TGF-beta-responsive promoter construct, p3TP-lux. Using the primary dermal fibroblasts, we also demonstrate that Smad3 is integral for induction of endogenous plasminogen activator inhibitor 1. We subsequently demonstrate that Smad3 null MEFs are partially resistant to TGF-beta's antiproliferative effect, thus firmly establishing a role for Smad3 in TGF-beta-mediated growth inhibition. We next examined cells in which Smad3 is most highly expressed, specifically cells of immune origin. Although no specific developmental defect was detected in the immune system of the Smad3 null mice, a functional defect was observed in the ability of TGF-beta to inhibit the proliferation of splenocytes activated by specific stimuli. In addition, primary splenocytes display defects in TGF-beta-mediated repression of cytokine production. These data, taken together, establish a role for Smad3 in mediating the antiproliferative effects of TGF-beta and implicate Smad3 as a potential effector for TGF-beta in modulating immune system function.  (+info)

Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. (5/637)

Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis. The FMF gene (MEFV) was cloned recently, and four missense mutations were identified. Here we present data from non-Ashkenazi Jewish and Arab patients in whom we had not originally found mutations and from a new, more ethnically diverse panel. Among 90 symptomatic mutation-positive individuals, 11 mutations accounted for 79% of carrier chromosomes. Of the two mutations that are novel, one alters the same residue (680) as a previously known mutation, and the other (P369S) is located in exon 3. Consistent with another recent report, the E148Q mutation was observed in patients of several ethnicities and on multiple microsatellite haplotypes, but haplotype data indicate an ancestral relationships between non-Jewish Italian and Ashkenazi Jewish patients with FMF and other affected populations. Among approximately 200 anonymous Ashkenazi Jewish DNA samples, the MEFV carrier frequency was 21%, with E148Q the most common mutation. Several lines of evidence indicate reduced penetrance among Ashkenazi Jews, especially for E148Q, P369S, and K695R. Nevertheless, E148Q helps account for recessive inheritance in an Ashkenazi family previously reported as an unusual case of dominantly inherited FMF. The presence of three frequent MEFV mutations in multiple Mediterranean populations strongly suggests a heterozygote advantage in this geographic region.  (+info)

Autoimmune lymphoproliferative syndrome with defective Fas: genotype influences penetrance. (6/637)

Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte homeostasis and immunological tolerance. Most patients have a heterozygous mutation in the APT1 gene, which encodes Fas (CD95, APO-1), mediator of an apoptotic pathway crucial to lymphocyte homeostasis. Of 17 unique APT1 mutations in unrelated ALPS probands, 12 (71%) occurred in exons 7-9, which encode the intracellular portion of Fas. In vitro, activated lymphocytes from all 17 patients showed apoptotic defects when exposed to an anti-Fas agonist monoclonal antibody. Similar defects were found in a Fas-negative cell line transfected with cDNAs bearing each of the mutations. In cotransfection experiments, Fas constructs with either intra- or extracellular mutations caused dominant inhibition of apoptosis mediated by wild-type Fas. Two missense Fas variants, not restricted to patients with ALPS, were identified. Variant A(-1)T at the Fas signal-sequence cleavage site, which mediates apoptosis less well than wild-type Fas and is partially inhibitory, was present in 13% of African American alleles. Among the ALPS-associated Fas mutants, dominant inhibition of apoptosis was much more pronounced in mutants affecting the intracellular, versus extracellular, portion of the Fas receptor. Mutations causing disruption of the intracellular Fas death domain also showed a higher penetrance of ALPS phenotype features in mutation-bearing relatives. Significant ALPS-related morbidity occurred in 44% of relatives with intracellular mutations, versus 0% of relatives with extracellular mutations. Thus, the location of mutations within APT1 strongly influences the development and the severity of ALPS.  (+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. (7/637)

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)

Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans. (8/637)

Since little is known about chromosomal locations harboring type 2 diabetes-susceptibility genes, we conducted a genomewide scan for such genes in a Mexican American population. We used data from 27 low-income extended Mexican American pedigrees consisting of 440 individuals for whom genotypic data are available for 379 markers. We used a variance-components technique to conduct multipoint linkage analyses for two phenotypes: type 2 diabetes (a discrete trait) and age at onset of diabetes (a truncated quantitative trait). For the multipoint analyses, a subset of 295 markers was selected on the basis of optimal spacing and informativeness. We found significant evidence that a susceptibility locus near the marker D10S587 on chromosome 10q influences age at onset of diabetes (LOD score 3.75) and is also linked with type 2 diabetes itself (LOD score 2.88). This susceptibility locus explains 63.8%+/-9.9% (P=. 000016) of the total phenotypic variation in age at onset of diabetes and 65.7%+/-10.9% (P=.000135) of the total variation in liability to type 2 diabetes. Weaker evidence was found for linkage of diabetes and of age at onset to regions on chromosomes 3p, 4q, and 9p. In conclusion, our strongest evidence for linkage to both age at onset of diabetes and type 2 diabetes itself in the Mexican American population was for a region on chromosome 10q.  (+info)

Institute of Cancer Research Repository - Genetic Diagnosis of High-Penetrance Susceptibility for Colorectal Cancer (CRC) Is...Institute of Cancer Research Repository - Genetic Diagnosis of High-Penetrance Susceptibility for Colorectal Cancer (CRC) Is...
Purpose Knowledge of the contribution of high-penetrance susceptibility to familial colorectal cancer (CRC) is relevant to the counseling, treatment, and surveillance of CRC patients and families. Patients and Methods To quantify the impact of germline mutation to familial CRC, we sequenced the mismatch repair genes (MMR) APC, MUTYH, and SMAD4/BMPR1A in 626 early-onset familial CRC cases ascertained through a population-based United Kingdom national registry. In addition, we evaluated the contribution of mutations in the exonuclease domain (exodom) of POLE and POLD1 genes that have recently been reported to confer CRC risk. Results Overall mutations (pathogenic, likely pathogenic) in MMR genes make the highest contribution to familial CRC (10.9%). Mutations in the other established CRC genes account for 3.3% of cases. POLE/POLD1 exodom mutations were identified in three patients with family histories consistent with dominant transmission of CRC. Collectively, mutations in the known genes account ...
Wiley: A Statistical Approach to Genetic Epidemiology: Concepts and Applications, with an e-Learning Platform, 2nd Edition -...Wiley: A Statistical Approach to Genetic Epidemiology: Concepts and Applications, with an e-Learning Platform, 2nd Edition -...
Foreword to the First Edition vii. Foreword to the Second Edition viii. Preface xi. Acknowledgments xv. 1 Molecular Genetics 1. 1.1 Genetic information 2. 1.1.1 Location of genetic information 2. 1.1.2 Interpretation of genetic information 5. 1.1.3 Translation of genetic information 5. 1.2 Transmission of genetic information 7. 1.3 Variations in genetic information 10. 1.3.1 Individual differences in genetic information 10. 1.3.2 Detection of variations 12. 1.3.3 Probability for detection of variations 16. 1.4 Problems 18. 2 Formal Genetics 21. 2.1 Mendel and his laws 22. 2.2 Segregation patterns 23. 2.2.1 Autosomal dominant inheritance 24. 2.2.2 Autosomal recessive inheritance 25. 2.2.3 X-chromosomal dominant inheritance 26. 2.2.4 X-chromosomal recessive inheritance 27. 2.2.5 Y-chromosomal inheritance 28. 2.3 Complications of Mendelian segregation 28. 2.3.1 Variable penetrance and expression 29. 2.3.2 Age-dependent penetrance 31. 2.3.3 Imprinting 33. 2.3.4 Phenotypic and genotypic heterogeneity ...
Plus itPlus it
Prostate cancer is estimated to have the largest heritable risk component of all common cancers, roughly twice that of breast cancer (1, 2). Family history remains the best clinical predictor of risk. Segregation analyses have been most consistent with a rare genetic component of age-dependent penetrance. The collective results of linkage studies of familial prostate cancer suggest complex heritability: incomplete penetrance (mutations associated with more modest effect sizes than typical of simple Mendelian disease), polygenic inheritance (multiple loci acting jointly to cause disease), and genetic heterogeneity (underlying causal mutations in many genes, each infrequent). These obstacles have posed a marked challenge for the discovery of gene mutations underlying familial prostate cancer. Genome-wide association studies (GWAS) of prostate cancer have detected validated risk variants, but these have been of low effect size (ORs, 1.1-2.0) and collectively have accounted for approximately 25% of ...
CRAN - Package FamEventCRAN - Package FamEvent
Simulates age-at-onset traits associated with a segregating major gene in family data obtained from population-based, clinic-based, or multi-stage designs. Appropriate ascertainment correction is utilized to estimate age-dependent penetrance functions either parametrically from the fitted model or nonparametrically from the data. The Expectation and Maximization algorithm can infer missing genotypes and carrier probabilities estimated from familys genotype and phenotype information or from a fitted model. Plot functions include pedigrees of simulated families and predicted penetrance curves based on specified parameter values.. ...
VackvSuG: The alternative method; diss the two L-suicide beta-substratesVackvSuG: The alternative method; diss the two L-suicide beta-substrates
To assess evidence for the presence of a mendelian pattern of familial transmission the presence of a rare major mendelian gene for PD for a gene that influences age-dependent penetrance of WD-repeat (GRWD1) belong to WD-repeat proteins that promotes microtubule dynamics activity somewhat still carried out, this may be true as far as mendelian (nuclear) genetic mechanisms are concerned that there was no highly penetrant mendelian pattern of inheritance here they show that DJ-1 and PSF bind and regulate the major interacting-proteins with DJ-1 in dopaminergic neuronal cells which can be reversed by wild-type DJ-1 [Drosophila gain-of-function mutants identified] to regulate the expression of a neuroprotective genetic program [1.] appears to have constrained the evolution of the nonA [diss-dissonance, plus the cacophony (referred to as intron L by them, [AFX1] as are inhibited by the L-type calcium channel blockers Dmca1A (nbA-cac) are both expressed in tubules] promoter. (PSF), paraspeckle ...
Submissions for variant NM 000059.4(BRCA2):c.4563A|G (p.Leu1521=) (rs206075) - ClinVar MinerSubmissions for variant NM 000059.4(BRCA2):c.4563A|G (p.Leu1521=) (rs206075) - ClinVar Miner
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease ...
Submissions for variant NM 015665.6(AAAS):c.819T|C (p.Asp273=) - ClinVar MinerSubmissions for variant NM 015665.6(AAAS):c.819T|C (p.Asp273=) - ClinVar Miner
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease ...
Variation in MAPT is not a contributing factor to the incomplete penetrance in LHON - ePrints - Newcastle UniversityVariation in MAPT is not a contributing factor to the incomplete penetrance in LHON - ePrints - Newcastle University
Full text for this publication is not currently held within this repository. Alternative links are provided below where available. ...
News | Rong Chen LabNews | Rong Chen Lab
Great News! Analysis of 589,306 genomes identifies individuals resilient to severe Mendelian childhood diseases was published on "Nature Biotechnology" in 11 April 2016. This paper did a comprehensive screen of 874 genes in 589,306 genomes led to the identification of 13 adults harboring mutations for 8 severe Mendelian conditions, with no reported clinical manifestation of the indicated disease. Findings demonstrate the promise of broadening genetic studies to systematically search for well individuals who are buffering the effects of rare, highly penetrant, deleterious mutations. Also indicate that incomplete penetrance for Mendelian diseases is likely more common than previously believed. The identification of resilient individuals may provide a first step toward uncovering protective genetic variants that could help elucidate the mechanisms of Mendelian diseases and new therapeutic strategies. Almost in the very first time when the paper posted online, a number of hits from major media ...
Usefulness of Genetic Testing in PD and PD Trials: A Balanced Review - IOS PressUsefulness of Genetic Testing in PD and PD Trials: A Balanced Review - IOS Press
An increasing proportion of the individual and population risk to develop Parkinsons disease (PD) can be explained by genetic variants of different effect strength, forming a continuum from rare high penetrance gain or loss of function mutations to
Penetrant Testing Courses | IMechE Argyll RuanePenetrant Testing Courses | IMechE Argyll Ruane
IMechE Argyll Ruane offer Penetrant Testing NDT training courses in Levels 1, 2 and 3 in a range of central and employer specific internationally recognised…
Current novel-gene-finding strategy for autosomal-dominant hypercholesterolaemia needs refinement | Journal of Medical GeneticsCurrent novel-gene-finding strategy for autosomal-dominant hypercholesterolaemia needs refinement | Journal of Medical Genetics
Methods and results For the ADH phenotype, subjects are considered as affected according to plasma cholesterol levels above the 95th percentile for age and gender. The disease penetrance is generally set at 0.9. These parameters were evaluated in 10 000 carriers of true pathogenic APOB and LDLR mutations and 20 000 relatives negative for the familial mutations. Application of the above parameters in almost a thousand families included in this study would have identified the causal variant in only 38% of all families. An average penetrance of 0.9 or higher, with a cut-point at the 95th percentile, was only observed for LDLR nonsense mutations. For APOB and LDLR missense mutations, a disease penetrance of 0.9 or higher is only expected, when total cholesterol and low-density lipoprotein cholesterol cut-points between the 75th and 90th percentile are used to determine an individuals disease status.. ...
Phenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjectsPhenotype, penetrance, and treatment of 133 cytotoxic T-lymphocyte antigen 4-insufficient subjects
Background: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a negative immune regulator. Heterozygous CTLA4 germline mutations can cause a complex immune dysregulation syndrome in human subjects. Objective: We sought to characterize the penetrance, clinical features, and best treatment options in 133 CTLA4 mutation carriers. Methods: Genetics, clinical features, laboratory values, and outcomes of treatment options were assessed in a worldwide cohort of CTLA4 mutation carriers. Results: We identified 133 subjects from 54 unrelated families carrying 45 different heterozygous CTLA4 mutations, including 28 previously undescribed mutations. Ninety mutation carriers were considered affected, suggesting a clinical penetrance of at least 67%;median age of onset was 11 years, and the mortality rate within affected mutation carriers was 16%(n = 15). Main clinical manifestations included hypogammaglobulinemia (84%), lymphoproliferation (73%), autoimmune cytopenia (62%), and respiratory (68%), gastrointestinal ...
Heterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood | JEMHeterozygous TBK1 mutations impair TLR3 immunity and underlie herpes simplex encephalitis of childhood | JEM
We have identified AD TBK1 deficiency as a new genetic etiology of HSE in childhood. The patients fibroblasts displayed impaired TLR3 responses, confirming the essential role of human TBK1 as an IFN-inducing IRF3 kinase in the TLR3 pathway in these cells. Together with our previous discoveries of AR UNC-93B (Casrouge et al., 2006), AR and AD TLR3 (Zhang et al., 2007; Guo et al., 2011), AR and AD TRIF (Sancho-Shimizu et al., 2011b), and AD TRAF3 (Pérez de Diego et al., 2010) deficiencies, this finding highlights the nonredundant role of TLR3-dependent IFN induction in the CNS for the control of HSV-1 in the course of primary infection in childhood. The clinical penetrance of AD TBK1 deficiency is incomplete, like that of AD TLR3, AR UNC-93B, and AD TRIF deficiencies, consistent with the sporadic occurrence of HSE (Whitley and Kimberlin, 2005). The actual clinical penetrance cannot be assessed, as the frequencies of the TBK1 mutant alleles are not known. We know only that they were not found in ...
Quantifying prion disease penetrance using large population control cohorts | Science Translational MedicineQuantifying prion disease penetrance using large population control cohorts | Science Translational Medicine
By Eric Vallabh Minikel, Sonia M. Vallabh, Monkol Lek, Karol Estrada, Kaitlin E. Samocha, J. Fah Sathirapongsasuti, Cory Y. McLean, Joyce Y. Tung, Linda P. C. Yu, Pierluigi Gambetti, Janis Blevins, Shulin Zhang, Yvonne Cohen, Wei Chen, Masahito Yamada, Tsuyoshi Hamaguchi, Nobuo Sanjo, Hidehiro Mizusawa, Yosikazu Nakamura, Tetsuyuki Kitamoto, Steven J. Collins, Alison Boyd, Robert G. Will, Richard Knight, Claudia Ponto, Inga Zerr, Theo F. J. Kraus, Sabina Eigenbrod, Armin Giese, Miguel Calero, Jesús de Pedro-Cuesta, Stéphane Haïk, Jean-Louis Laplanche, Elodie Bouaziz-Amar, Jean-Philippe Brandel, Sabina Capellari, Piero Parchi, Anna Poleggi, Anna Ladogana, Anne H. ODonnell-Luria, Konrad J. Karczewski, Jamie L. Marshall, Michael Boehnke, Markku Laakso, Karen L. Mohlke, Anna Kähler, Kimberly Chambert, Steven McCarroll, Patrick F. Sullivan, Christina M. Hultman, Shaun M. Purcell, Pamela Sklar, Sven J. van der Lee, Annemieke Rozemuller, Casper Jansen, Albert Hofman, Robert Kraaij, Jeroen G. J. ...
Genetic and phenotypic variationGenetic and phenotypic variation
For example, there is 70% penetrance if only 700 individuals express red phenotype out of 1,000 HairredHairred individuals. If penetrance of a phenotype is not 100%, then it has reduced penetrance. Mechanisms of reduced penetrance are not always clear. Expressivity is another important concept in describing genotype-phenotype correlation. Expressivity describes the severity of a phenotype among individuals with the same genotype. For example, if a condition has variable expressivity then one individual might have mild symptoms while another might have severe symptoms (although they have the same genotype). If a trait has constant expressivity then individuals with the same genotype will have the same degree of symptoms.. Mechanisms of variable expressivity are not always clear. Although there is typically a clear genotype-phenotype correlation that associates a specific allele with a specific phenotype, this link is frequently muddled. Even individuals with identical genotypes can have different ...
IS-052 Genetic Theory Of Infectious Diseases | Archives of Disease in ChildhoodIS-052 Genetic Theory Of Infectious Diseases | Archives of Disease in Childhood
The hypothesis that inborn errors of immunity underlie infectious diseases is gaining experimental support. However, the apparent modes of inheritance of predisposition or resistance differ considerably between diseases and between studies. A coherent genetic architecture of infectious diseases is lacking. We suggest here that life-threatening infectious diseases in childhood, occurring in the course of primary infection, result mostly from individually rare but collectively diverse single-gene variations of variable clinical penetrance, whereas the genetic component of predisposition to secondary or reactivation infections in adults is more complex. This model is consistent with (i) the high incidence of most infectious diseases in early childhood, followed by a steady decline, (ii) theoretical modelling of the impact of monogenic or polygenic predisposition on the incidence distribution of infectious diseases before reproductive age, (iii) available molecular evidence from both monogenic and ...
Publications - Trinity Research : Trinity College DublinPublications - Trinity Research : Trinity College Dublin
Molloy A, Kimmich O, Williams L, Butler JS, Byrne N, Molloy F, Moore H, Healy DG, Lynch T, Edwards MJ, Walsh C, Reilly RB, ORiordan S, Hutchinson M, An evaluation of the role of environmental factors in the disease penetrance of cervical dystonia., Journal of neurology, neurosurgery, and psychiatry, 86, (3), 2015, p331-335 ...
beaglebeagle
Please be aware that other genetic diseases or developmental abnormalities may still be present. A genetic test does not replace the need for ongoing clinical assessment by a veterinarian. Disease penetrance and clinical assessment of affected animals can only be performed by a qualified veterinarian ...
postnatal lethality, complete penetrance Mammalian Phenotype Term (MP:0011085)postnatal lethality, complete penetrance Mammalian Phenotype Term (MP:0011085)
The Mammalian Phenotype (MP) Ontology is a community effort to provide standard terms for annotating phenotypic data. You can use this browser to view terms, definitions, and term relationships in a hierarchical display. Links to summary annotated phenotype data at MGI are provided in Term Detail reports.
The survival gene MED4 explains low penetrance retinoblastoma in patients with large RB1 deletion. | Sigma-AldrichThe survival gene MED4 explains low penetrance retinoblastoma in patients with large RB1 deletion. | Sigma-Aldrich
Sigma-Aldrich offers abstracts and full-text articles by [Catherine Dehainault, Alexandra Garancher, Laurent Castéra, Nathalie Cassoux, Isabelle Aerts, François Doz, Laurence Desjardins, Livia Lumbroso, Rocío Montes de Oca, Geneviève Almouzni, Dominique Stoppa-Lyonnet, Celio Pouponnot, Marion Gauthier-Villars, Claude Houdayer].
One half dominant trait | Physics Forums - The Fusion of Science and CommunityOne half dominant trait | Physics Forums - The Fusion of Science and Community
Id think incomplete dominance, or alternatively variable penetrance, would be good possibilities that might explain the situation. For some reason, the musculature that creates a dimple on one side of your face, developed fdifferently on the other side, because the dominant gene that gives you a dimple, is not expressed to the same extent ( or not interpreted in the same way) on the other side ...
TGF-β Signaling Alterations and Colon Cancer | SpringerLinkTGF-β Signaling Alterations and Colon Cancer | SpringerLink
Colorectal cancer is the second most common cause of cancer-related death in the United States. Twin studies suggest that 35% of all colorectal cancer cases are inherited. High-penetrance tumor suscep
rs61751103 - SNPediars61751103 - SNPedia
The rs61751103(G) allele was found in 11 of 16 individuals affected by Alzheimers disease (average onset age 69.5 years) from seven late-onset AD families. This mutation was also found in at least one unaffected subject, implying incomplete penetrance. This SNP is referred to as i6006818 by 23andMe. ...
Biology-Online • View topic - Dominance but not majority? Why?!Biology-Online • View topic - Dominance but not majority? Why?!
Even though polydactyly is controlled by a dominant allele it is accompanied by incomplete penetrance hence not observed in majority of the population. The gene doesnot penetrate or show the phenotype associated with the genotype in all the individuals with that genotype ...
012654 - B6.Cg-Dsht/GrsrJ012654 - B6.Cg-Dsht/GrsrJ
|i|Dsht|/i| heterozygotes have tails that are shortened and kinked or curled, and some have white belly spots or eye defects. Genetic background significantly impacts penetrance.
born imaginative.: Thrifted. Updates. Pics.born imaginative.: Thrifted. Updates. Pics.
If I could wear my kids out and they fall asleep at 6:30 everynight, oh my Id get things accomplished. After finishing her May dress (pics to come), dishes, a couple loads of laundry, hand sawing two small trees down, spending a bunch of time removing the overgrown forsythia, preparing some snail mail for loved ones, it was only 9:30. Its amazing how fast things get done without helpers! And then I was petered out ...
Biochemical basis for dominant inheritance, variable penetrance, and maternal effects in RBP4 congenital eye disease<...Biochemical basis for dominant inheritance, variable penetrance, and maternal effects in RBP4 congenital eye disease<...
TY - JOUR. T1 - Biochemical basis for dominant inheritance, variable penetrance, and maternal effects in RBP4 congenital eye disease. AU - Chou, Christopher M.. AU - Nelson, Christine. AU - Tarlé, Susan A.. AU - Pribila, Jonathan T.. AU - Bardakjian, Tanya. AU - Woods, Sean. AU - Schneider, Adele. AU - Glaser, Thomas M. PY - 2015/4/23. Y1 - 2015/4/23. N2 - Gestational vitamin A (retinol) deficiency poses a risk for ocular birth defects and blindness. We identified missense mutations in RBP4, encoding serum retinol binding protein, in three families with eye malformations of differing severity, including bilateral anophthalmia. The mutant phenotypes exhibit dominant inheritance, but incomplete penetrance. Maternal transmission significantly increases the probability of phenotypic expression. RBP normally delivers retinol from hepatic stores to peripheral tissues, including the placenta and fetal eye. The disease mutations greatly reduce retinol binding to RBP, yet paradoxically increase the ...
No evidence that rare coding variants in ZNF804A confer risk of schizophrenia -ORCANo evidence that rare coding variants in ZNF804A confer risk of schizophrenia -ORCA
Strong evidence that rare variants of relatively high penetrance are involved in the etiology of schizophrenia is currently restricted to the data from studies investigating copy number variants and major structural re-arrangements in that disorder. Global tests of the hypothesis of the involvement of fairly high penetrance rare single nucleotide changes or small insertion deletion events await the genesis of data from large-scale sequencing studies, meanwhile, a pragmatic approach to trying to detect such alleles is to target sequencing efforts on genes for which there is compelling evidence from other sources for their involvement in this disorder. We have undertaken a study, which aimed to identify whether rare (frequency ∼0.001%) coding variants in the schizophrenia susceptibility gene ZNF804A are involved in this disorder. We screened the coding regions of the gene in 517 schizophrenic cases and 501 controls, and genotyped rare non-synonymous variants in a case-control sample powered to ...
Rare variants as low-penetrance risk alleles for colorectal cancer | The Family History of Bowel Cancer ClinicRare variants as low-penetrance risk alleles for colorectal cancer | The Family History of Bowel Cancer Clinic
Rare variants as low-penetrance alleles Rare variants will not be detectable by population association studies based on the use of linked polymorphic markers, even with very large case/control cohort studies. This is because of low allelic frequency and individually small contributions to the overall inherited susceptibility of a disease. These variants are less common…
Semen Analysis - X-ray, hamster-egg penetrance assay Laguna Niguel, CASemen Analysis - X-ray, hamster-egg penetrance assay Laguna Niguel, CA
At Acacio Fertility Centers, Dr. Brian Acacio offers semen analysis, x-ray, hamster-egg penetrance assay Aliso Viejo, Laguna Hills, Laguna Niguel, Mission Viejo and Bakersfield.
Abstract 15418: Mir590 Variant rs6971711 Identified in African-American HCM Patients Reduces Mature MiR590 Biogenesis and...Abstract 15418: Mir590 Variant rs6971711 Identified in African-American HCM Patients Reduces Mature MiR590 Biogenesis and...
Hypertrophic cardiomyopathy (HCM), the most common inherited cardiovascular disorders characterized by myocyte hypertrophy/disarray and fibrosis. Genotype-phenotype correlations indicate phenotypic heterogeneity and variable penetrance, indicating influence of modifier genes. Recent studies reveal that variants in microRNAs (miRs) can lead to disease.. Aim: The goal was to identify genetic variations in miRs that could have functional effects, in HCM patients.. Methods: Direct sequencing of 18 miRs (selected by literature mining) was performed in 199 HCM patients. The 1000 Genomes Project database was used to obtain matched population allele and genotype frequency. Real-time qPCR and luciferase assay were performed in HEK293T cells to assess functional effects of the miR variant.. Results: Eleven variants in 9/18 miRs were identified in 89 HCM patients. Our novel result is a SNP rs6971711(72C,T), located in mature miR-590-3p, a regulator of post-natal cardiac myocyte proliferation. This SNP was ...
ARTICLES | PhysiologyARTICLES | Physiology
The mechanisms linking Cl− channel dysfunction to the macular dystrophy that ensues is not clear. This is partly because visual acuity in Best disease patients is highly variable. For example, in one family, an elderly mother had normal visual acuity of 20/20, whereas her daughter and three grandchildren had clinical symptoms as early as age 5, even though all had the same genotype (R218C/+) (10). Despite the variable penetrance of disease symptoms, virtually all individuals with bestrophin gene mutations exhibit abnormal EOGs (81). This suggests that other factors, genetic or environmental, must contribute to the development of retinal lesions. However, the fact that an abnormal EOG is a consistent feature of the disease but that degraded visual acuity is more variable provides a strong argument that Cl− channel dysfunction precedes macular degeneration.. Because an abnormal EOG is unambiguously linked to hBest1 mutations, it would be useful to understand the mechanism of the light peak, ...
Penetrance of Hypertrophic Cardiomyopathy in Children and AdolescentsClinical Perspective | CirculationPenetrance of Hypertrophic Cardiomyopathy in Children and AdolescentsClinical Perspective | Circulation
Methods and Results-Ninety probands and 361 relatives were included in a family screening program for HCM (1994-2001). Eleven sarcomere genes, CRYAB, α-GAL, and titin were screened. Sixty-six relatives and 4 probands were ,18 years of age at inclusion. Twelve child relatives were mutation carriers (age, 12 ± 5 years), and 26 had unknown genetic status, ie, relatives from families without identified mutations (n = 21) or not tested (n = 5) (age, 11 ± 5 years). Twenty-eight noncarriers (42%; age, 10 ± 4 years) served as control subjects. Two of 38 child relatives (5%) at risk of developing HCM fulfilled diagnostic criteria for HCM at inclusion. After 12 ± 1 years of follow-up, 2 of the 36 (6%; 95% confidence interval, 2-18) at-risk child relatives who were phenotype negative at inclusion had developed the HCM phenotype at 26 and 28 years of age. During follow-up, none of the child relatives experienced serious cardiac events. Participation in the screening program had no long-term negative ...
White-matter correlates of gene penetrance reveal key brain circuits for dystonia | Genes 2 Brains 2 Mind 2 MeWhite-matter correlates of gene penetrance reveal key brain circuits for dystonia | Genes 2 Brains 2 Mind 2 Me
Image via Wikipedia Within the genetic news flow, there is often, and rightly so, much celebration when a gene for a disease is identified. This is indeed an important first step, but often, the slogging from that point to a treatment - and the many small breakthroughs along the way - can go unnoticed. One…
Human Genotyping-CEGEN Unit: Publications in the last five years | cnio.esHuman Genotyping-CEGEN Unit: Publications in the last five years | cnio.es
Gracia-Aznarez FJ, Fernandez V, Pita G, Peterlongo P, Dominguez O, de la Hoya M, Duran M, Osorio A, Moreno L, Gonzalez-Neira A, Rosa-Rosa JM, Sinilnikova O, Mazoyer S, Hopper J, Lazaro C, Southey M, Odefrey F, Manoukian S, Catucci I, Caldes T, Lynch HT, Hilbers FS, van Asperen CJ, Vasen HF, Goldgar D, Radice P, Devilee P, Benitez J (2013). Whole exome sequencing suggests much of non-BRCA1/BRCA2 familial breast cancer is due to moderate and low penetrance susceptibility alleles. PLoS ONE 8, e55681 ...
The Pathophysiology of Moyamoya Disease: An UpdateThe Pathophysiology of Moyamoya Disease: An Update
The exact function of RNF213 is unknown. Recent in vivo experiments using genetically engineered RNF213 mice addressed the mechanism underlying the RNF213 SNPs in the development of MMD pathology. The target disruption of RNF213 did not induce MMD in the RNF213-defcient mice under normal conditions [33]. Kanoke and colleagues alternatively generated RNF213-knock-in mice that expressed a missense mutation in the mouse RNF213, p.R4828K, on Exon 61, which corresponds to the human RNF213, p.R4859K, on Exon 60 in MMD patients; however, these mice did not develop MMD under normal conditions [34]. These negative results could be consistent with the low penetrance rate of the RNF213 polymorphisms in patients with MMD, and may indicate the importance of environmental factors in addition to the genetic factors [35]. They subjected the RNF213-deficient mice to an ischemic insult, and found that the post-ischemic angiogenesis was significantly enhanced in the mice lacking RNF213 after a chronic hindlimb ...
Penetrant testing (PT) - Non-destructive testing of materials and structures (NDT) | TÜV NORD LatvijaPenetrant testing (PT) - Non-destructive testing of materials and structures (NDT) | TÜV NORD Latvija
Penetrant method of non-destructive testing is dedicated to detecting surface defects invisible to the naked eye. It is based on use of capillary properties of liquids (namely, on capillary penetration of special indicator liquids inside defects). This method reveals defects by forming an indication patterns on the surface of tested items. These patterns have high optical (luminance and color) contrast and width exceeding width of the defect opening. When performing testing a special wetting liquid (penetrating liquid, penetrant) is applied on the surface of the tested item. By impact of capillary forces this liquid fills cavities of surface defects and then it is removed from the tested area. Defects are detected already by applying a developer to the surface of the tested area. The developer absorbs penetrant remaining in cavities of defects. As a result of this process, there is either a red indication pattern appears on the developers white background (dye penetrant testing) or a ...
iBeetleiBeetle
The search at iBeetle-Base allows for very specific searches (e.g. "larva, leg, size decreased"). However, in order not to miss interesting phenotypes, we recommend initiating your search broadly for defects of the structure and stage you are interested in (larva, leg). Further, a penetrance of ,50% is recommended in order to increase the portion of reproducible datasets. Next, the list should be consolidated by browsing the pictures and detailed annotations displayed in the search results. Interesting results can be marked by checkboxes. Finally, the respective details pages should be browsed in order to learn more about additional phenotypes, the gene structure and sequences and its orthologs ...
iBeetleiBeetle
The search at iBeetle-Base allows for very specific searches (e.g. "larva, leg, size decreased"). However, in order not to miss interesting phenotypes, we recommend initiating your search broadly for defects of the structure and stage you are interested in (larva, leg). Further, a penetrance of ,50% is recommended in order to increase the portion of reproducible datasets. Next, the list should be consolidated by browsing the pictures and detailed annotations displayed in the search results. Interesting results can be marked by checkboxes. Finally, the respective details pages should be browsed in order to learn more about additional phenotypes, the gene structure and sequences and its orthologs ...
A novel mutation in the cardiac myosin-binding protein C gene is responsible for hypertrophic cardiomyopathy with severe...A novel mutation in the cardiac myosin-binding protein C gene is responsible for hypertrophic cardiomyopathy with severe...
It has been demonstrated previously that clinical phenotypes of HCM (hypertrophic cardiomyopathy) caused by mutations in the cardiac MyBP-C (myosin-binding protein C) gene show late onset, low penetrance and favourable clinical course. However, we have encountered severe phenotypes in several carriers of the MyBP-C gene mutations. The aim of the present study was to screen novel MyBP-C gene mutations in patients with HCM and to investigate the genetic differences in affected subjects with severe phenotypes. The MyBP-C gene was screened in 292 Japanese probands with HCM, and a novel c.2067+1G→A mutation was present in 15 subjects in five families. Clinical phenotypes of carriers of the c.2067+1G→A mutation were compared with those of a previously identified Arg820Gln (Arg820→Gln) mutation in the MyBP-C gene. The disease penetrance in subjects aged ≥30 years was 90% in carriers of the c.2067+1G→A mutation and 61% in carriers of the Arg820Gln mutation. Sudden death occurred in four ...
Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes |...Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes |...
ABSTRACT: BACKGROUND: Recent advances in whole-genome association studies (WGASs) for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined. METHODS: We applied an integrative approach for identifying candidate low-penetrance breast cancer susceptibility genes, their characteristics and molecular networks through the analysis of diverse sources of biological evidence. RESULTS: First, examination of the distribution of Gene Ontology terms in ordered WGAS results identified ...
From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic...From incomplete penetrance with normal telomere length to severe disease and telomere shortening in a family with monoallelic...
PARN encodes poly(A)-specific ribonuclease. Biallelic and monoallelic PARN variants are associated with Hoyeraal-Hreidarsson syndrome/dyskeratosis congenita and idiopathic pulmonary fibrosis (IPF), respectively. The molecular features associated with incomplete penetrance of PARN-associated IPF have not been described. We report a family with a rare missense, p.Y91C, and a novel insertion, p.(I274*), PARN variant. We found PARN p.Y91C had reduced deadenylase activity and the p.(I274*) transcript was depleted. Detailed analysis of the consequences of these variants revealed that, while PARN protein was lowest in the severely affected biallelic child who had the shortest telomeres, it was also reduced in his mother with the p.(I274*) variant but telomeres at the 50th percentile. Increased adenylation of telomerase RNA, human telomerase RNA, and certain small nucleolar RNAs, and impaired ribosomal RNA maturation were observed in cells derived from the severely affected biallelic carrier, but not in ...
Institute of Cancer Research Repository - Glutathione-S-transferase M1, T1 and P1 polymorphisms, and breast cancer risk, in...Institute of Cancer Research Repository - Glutathione-S-transferase M1, T1 and P1 polymorphisms, and breast cancer risk, in...
Variation in penetrance estimates for BRCA1/2 carriers suggests that other environmental and genetic factors may modify cancer risk in carriers. The GSTM1, T1 and P1 isoenzymes are involved in metabolism of environmental carcinogens. The GSTM1 and GSTT1 gene is absent in a substantial proportion of the population. In GSTP1, a single-nucleotide polymorphism that translates to Ile112Val was associated with lower activity. We studied the effect of these polymorphisms on breast cancer (BC) risk in BRCA1/2 carriers. A population of 320 BRCA1/2 carriers were genotyped; of them 262 were carriers of one of the three Ashkenazi founder mutations. Two hundred and eleven were affected with BC (20 also with ovarian cancer (OC)) and 109 were unaffected with BC (39 of them had OC). Risk analyses were conducted using Cox proportional hazard models adjusted for origin (Ashkenazi vs non-Ashkenazi). We found an estimated BC HR of 0.89 (95% CI 0.65-1.12, P = 0.25) and 1.11 (95% CI 0.81-1.52, P = 0.53) for the null ...
Association of the mtDNA m.4171C|A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions | BMC Neurology |...Association of the mtDNA m.4171C|A/MT-ND1 mutation with both optic neuropathy and bilateral brainstem lesions | BMC Neurology |...
We report the association of the m.4171C,A/MT-ND1 LHON mutation with bilateral lesions of the brainstem resembling Leigh syndrome associated with acute onset of vomiting and vertigo, in addition to subacute bilateral loss of central vision, typical of LHON. This case extends the clinical features associated with this rare mutation, previously reported only in association with pure LHON, [8-11] and reissues the unexplained wide variability in severity of homoplasmic mtDNA mutations [2]. This family is the sixth maternal lineage carrying this rare mutation, the second on a European mtDNA background. Non-synonymous mtDNA variants, in particular those affecting complex I and III subunit genes, have been implicated in both variable penetrance and severity of LHON clinical expression [7, 12]. For example, one LHON family from China carrying the m.4171C,A/MT-ND1 and the m.14841A , G/MT-ND6 variant, showed an almost complete penetrance, unusual for LHON [11]. Our genetic analysis also supports the ...
Interacciones genéticas y genético-ambientales como efecto modificador del riesgo de cáncer de próstata: un diseño «case-only»Interacciones genéticas y genético-ambientales como efecto modificador del riesgo de cáncer de próstata: un diseño «case-only»
CACERES L, Dante et al. Gene-gene and gene-environment interactions as modifier factors of prostatic cancer risk: «a case-only» design study . Rev. méd. Chile [online]. 2004, vol.132, n.8, pp.961-970. ISSN 0034-9887. http://dx.doi.org/10.4067/S0034-98872004000800008.. Background: The role of susceptibility low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear, but may involve in some cases multiple alleles at multiple loci. Aim: To evaluate the association of gene-gene and gene-environment interactions with PCa. Patients and methods: One hundred three subjects with biopsy proven PCa were studied, using a case-only design. All were interrogated about smoking habits. Polymorphisms for Glutathione-S-transferase (GST) and Cytochrome P4501A1 (CYP1A1), were measured in DNA extracted from peripheral Iymphocytes, using a restriction fragment length polymorphism analysis. Results: Our findings suggest that gene-gene interactions between GSTT1 and CYP1A1 ...
Interacciones genéticas y genético-ambientales como efecto modificador del riesgo de cáncer de próstata: un diseño «case-only»Interacciones genéticas y genético-ambientales como efecto modificador del riesgo de cáncer de próstata: un diseño «case-only»
CACERES L, Dante et al. Gene-gene and gene-environment interactions as modifier factors of prostatic cancer risk: «a case-only» design study . Rev. méd. Chile [online]. 2004, vol.132, n.8, pp.961-970. ISSN 0034-9887. http://dx.doi.org/10.4067/S0034-98872004000800008.. Background: The role of susceptibility low penetrance genes and environmental factors in the etiology of prostate cancer (PCa) is unclear, but may involve in some cases multiple alleles at multiple loci. Aim: To evaluate the association of gene-gene and gene-environment interactions with PCa. Patients and methods: One hundred three subjects with biopsy proven PCa were studied, using a case-only design. All were interrogated about smoking habits. Polymorphisms for Glutathione-S-transferase (GST) and Cytochrome P4501A1 (CYP1A1), were measured in DNA extracted from peripheral Iymphocytes, using a restriction fragment length polymorphism analysis. Results: Our findings suggest that gene-gene interactions between GSTT1 and CYP1A1 ...
NEK11 as a candidate high-penetrance melanoma susceptibility gene | Journal of Medical GeneticsNEK11 as a candidate high-penetrance melanoma susceptibility gene | Journal of Medical Genetics
Here, a novel nonsense protein truncating variant (PTV) in NEK11 p.Arg374Ter was identified as a possible familial melanoma predisposition mutation in a Dutch family. The possibility of any other potentially damaging variants found by WES in this family to either be causal or contributing to the melanoma-risk of this family was considered. Since not enough scientific evidence was available to support a contributing role, these variants were not investigated further.. NEK11 has been initially characterised as a DNA-damage response kinase with two isoforms, the full-length isoform consisting of 645 residues (NEK11-FL) and the short isoform consisting of 470 residues (NEK11-S).37 A regulatory effect during IR-induced G2/M cell-cycle arrest has been described, that is, NEK11 was shown to be involved in phosphorylation of CDC25A triggering its degradation and ultimate blocking of progression into mitosis.27 38 40 NEK11 has been described to (de) regulate G2/M cell-cycle arrest in colorectal carcinoma ...
Early-onset Crohns disease and autoimmunity associated with a variant in CTLA-4. | IKMBEarly-onset Crohn's disease and autoimmunity associated with a variant in CTLA-4. | IKMB
Our results support the concept that variants in CTLA4 provide the basis for a novel Mendelian form of early-onset CD associated with systemic autoimmunity. Incomplete penetrance of autoimmunity further indicates the presence of other genetic and/or environmental modifiers.A novel missense variant was identified in CTLA4 encoding CTLA-4, a coinhibitory protein expressed by T cells and required for regulation of T cell activation. The residue affected by the mutation, CTLA-4 Tyr60, is evolutionarily highly conserved, and the identified Y60C variant is predicted to affect protein folding and structural stability and demonstrated to cause impaired CTLA-4 dimerisation and CD80 binding. Intestinal inflammation and autoimmunity in carriers of CTLA-4 Y60C exhibit incomplete penetrance with a spectrum of clinical presentations ranging from asymptomatic carrier status to fatal autoimmunity and intestinal inflammation. In a clinically affected CTLA-4 Y60C carrier, T cell proliferation was increased in ...
JCI - Paget disease of boneJCI - Paget disease of bone
Several observations suggest that environmental factors may also contribute to the pathogenesis of PD. The variable penetrance of PD within families with a genetic predisposition to PD, the observation that the disease remains highly localized to a particular bone or bones rather than affecting the entire skeleton, and the fact that the incidence and severity of the disease has been changing over the last 25 years (83, 84) all support the hypothesis that additional, nongenetic factors are involved in the development of PD. PD affected approximately 2-8% of the population in the United Kingdom and New Zealand 20 years ago, but recent studies of the prevalence of PD in subjects of European origin in 2 New Zealand cities found that the prevalence of PD was about half of what had been estimated 25 years ago (84). Similarly, Van Staa and coworkers recently conducted a radiologic survey in 10 British cities and found a decrease in the incidence of PD compared with the findings of the original studies ...
Hepatocellular carcinoma and the penetrance of HFEC282Y mutations: a cross sectional study | Springer for Research & DevelopmentHepatocellular carcinoma and the penetrance of HFEC282Y mutations: a cross sectional study | Springer for Research & Development
Background Although most patients with hereditary haemochromatosis have HFE C282Y mutations, the lifetime risk to HFEC282Y homozygotes of developing fatal diseases such as hepatocellular carcinoma...
NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020 in: Journal of...NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020 in: Journal of...
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panels discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry. ...
PSEN1 I143F | ALZFORUMPSEN1 I143F | ALZFORUM
This mutation was found in a family from the UK with an autosomal dominant pattern of AD inheritance and a median age at onset of 55 years (Rossor et al., 1996; Palmer et al., 1999). The mutation was present in three members with AD, as well as in a member who was symptom-free at age 68, suggesting incomplete penetrance. The mutation was absent from 96 white controls. The affected mutation carriers had disease onset at 53, 55, and 59 years of age, with clinical features fulfilling the NINCDS criteria for probable AD. APOE genotyping revealed that all three mutation carriers were homozygous for the E3 allele. The mutation was also reported in an individual with age at onset of 51 years, and disease duration of six years (Gómez-Isla et al., 1999).. Neuropathology ...
Phänotypische und genotypische Charakterisierung der ENU-induzierten Mausmutante SMA002 als Tiermodell für Wachstumsdefizit und...Phänotypische und genotypische Charakterisierung der ENU-induzierten Mausmutante SMA002 als Tiermodell für Wachstumsdefizit und...
This thesis describes the phenotypic and genotypic analysis of the dominant mutation in the ENU-induced mutant mouse line SMA002. The results were derived from the analysis of heterozygous mutant animals on the C3H genetic background. As the main phenotype of SMA002, an abnormal behavior combined with reduced body weight was revealed. The mutant phenotype showed complete penetrance in all generations analyzed. Abnormal behavior, as the most prominent phenotype was characterized by the occurrence of restlessness and an increased grooming behavior. The grooming behavior was increased fivefold but did not always contain all aspects of the standard repertoire. Pathological examinations of the skin and the analysis of parameters of the immune system indicated that this behavior was not caused by an allergic reaction. Clinical examination of the animals revealed a significant difference in body weight between mutant and control littermates. The body weight of the mutant animals was about 30% lower ...
NewYork-Presbyterian Queens - Genetics and Cancer - DNA Testing For Cancer Genetic Susceptibility GenesNewYork-Presbyterian Queens - Genetics and Cancer - DNA Testing For Cancer Genetic Susceptibility Genes
However, ASCO also acknowledges that emerging technologies, like genomic profiling for low penetrance genetic variants (markers of very low disease risk), may be appropriate for some patients who do not have a personal or family history that suggests a higher risk of cancer. People may undergo genetic testing using direct-to-consumer (DTC) tests, but they may ask their health care providers for help in interpreting the test results and obtaining follow-up care. For any genetic test, ASCO urges doctors and other health care providers to recommend follow-up care that is based on established cancer risk factors such as family history, behavioral factors, environmental exposures, and scientifically-validated tests for cancer risks.. ASCO further states that although the list of genes for cancer susceptibility syndromes continues to grow, the ever-changing nature of the field highlights the importance of getting genetic counseling both before and after doing genetic testing. Companies that offer DTC ...
Penetrance?Penetrance?
What is the general view of the term and phenomena of penetrance? This refers to differential expression of a phenotype under various environmental conditions or genetic backgrounds, although the genotype of a plant or line is the same. It seems to be a rather vague term. My question arises because I may be seeing differing penetrance of flowering genes in Poa annua due to environment and genetic background. PJ john0130 at gold.tc.umn.edu ...
Hozelock Compact Enclosed 2 in 1 Hose Reel at wilko.comHozelock Compact Enclosed 2 in 1 Hose Reel at wilko.com
Hozelock Compact Enclosed 2 in 1 Hose Reel - This innovative Hozelock 2in1 Compact Hose Reel comes supplied with 25m of multi-purpose hose. With an enclosed casing, the hose is protected during storage ensuring the life of the hose. This hose reel can be freestanding or wall mounted. Made from the highest quality plastics, the 25m 2in1 Compact Hose Reel will stand the hard wearing challenge of gardening tasks, time after time. It comes with a 2 year manufacturer warranty. This Hozelock 25m 2in1 Compact Reel has an easy rewind action and includes a viewing window that allows for full control and stress free rewinding. A folding carry handle ensures the reel is fully portable and is designed to be quickly and easily assembled. The Compact Reel also contains a Hose Nozzle, Threaded Tap Connector for outdoor taps that are 3/4 inch and 1/2 inch, Hose End Connector and Waterstop Connector. The Nozzle is adjustable from jet for a high volume of water which is great for filling
AST PENETRANT II - Aerosol - American Patriot Sales And ServiceAST PENETRANT II - Aerosol - American Patriot Sales And Service
Heavy-duty, industrial strength penetrant. It quickly penetrates deep through rust, scale, and corrosion. Will free metal parts faster than ordinary penetrants/lubricants. No CFCs, chlorinated solvents, or silicones ...
E-mail a Wiley Online Library LinkE-mail a Wiley Online Library Link
David Gosal, Timothy Lynch, Owen A. Ross, Kristoffer Haugarvoll, Matthew J. Farrer and J. Mark Gibson Global distribution and reduced penetrance: Lrrk2 R1441C in an Irish Parkinsons disease kindred Movement Disorders 22. Version of Record online: 6 NOV 2006 , DOI: 10.1002/mds.21200. Complete the form below and we will send an e-mail message containing a link to the selected article on your behalf. Required = Required Field. ...
Death, Sudden, Cardiac | Harvard Catalyst Profiles | Harvard CatalystDeath, Sudden, Cardiac | Harvard Catalyst Profiles | Harvard Catalyst
Parikh VN, Caleshu C, Reuter C, Lazzeroni LC, Ingles J, Garcia J, McCaleb K, Adesiyun T, Sedaghat-Hamedani F, Kumar S, Graw S, Gigli M, Stolfo D, Dal Ferro M, Ing AY, Nussbaum R, Funke B, Wheeler MT, Hershberger RE, Cook S, Steinmetz LM, Lakdawala NK, Taylor MRG, Mestroni L, Merlo M, Sinagra G, Semsarian C, Meder B, Judge DP, Ashley E. Regional Variation in RBM20 Causes a Highly Penetrant Arrhythmogenic Cardiomyopathy. Circ Heart Fail. 2019 03; 12(3):e005371 ...
HFE hereditary haemochromatosisHFE hereditary haemochromatosis
Frontotemporal dementia and parkinsonism linked to chromosome 17Frontotemporal dementia and parkinsonism linked to chromosome 17
Cerebellothalamic tractCerebellothalamic tract
BRCA mutationBRCA mutation
Marfan syndromeMarfan syndrome
HypodysfibrinogenemiaHypodysfibrinogenemia
HuntingtinHuntingtin
CTLA-4CTLA-4
Familial Mediterranean feverFamilial Mediterranean fever
Birt-Hogg-Dubé syndromeBirt-Hogg-Dubé syndrome
Fibrodysplasia ossificans progressivaFibrodysplasia ossificans progressiva
Cat body-type mutationCat body-type mutation
Maturity onset diabetes of the youngMaturity onset diabetes of the young
Human geneticsHuman genetics
Expressivity (genetics)Expressivity (genetics)
Generalized epilepsy with febrile seizures plusGeneralized epilepsy with febrile seizures plus
Malignant hyperthermiaMalignant hyperthermia
Hereditary multiple exostosesHereditary multiple exostoses
Spasmodic torticollisSpasmodic torticollis
Distal 18q-Distal 18q-
Candidate geneCandidate gene
CDKN2ACDKN2A
Vitelliform macular dystrophyVitelliform macular dystrophy
Huntingtons diseaseHuntington's disease
Von Hippel-Lindau diseaseVon Hippel-Lindau disease
Lebers hereditary optic neuropathyLeber's hereditary optic neuropathy
Cryopyrin-associated periodic syndromeCryopyrin-associated periodic syndrome
DysfibrinogenemiaDysfibrinogenemia
Pseudodeficiency allelesPseudodeficiency alleles
Boxer cardiomyopathyBoxer cardiomyopathy
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsAnthropology, Education, Sociology and Social PhenomenaNamed GroupsHealth Care
PenetrancePedigreeGenes, DominantHeterozygoteMutationPhenotypeGenetic LinkageGenetic Predisposition to DiseaseOptic Atrophy, Hereditary, LeberLod ScoreAllelesGerm-Line MutationFamily HealthGenotypeDNA Mutational AnalysisGenetic TestingGenes, BRCA1Genes, ModifierModels, GeneticAge of OnsetFounder EffectHirschsprung DiseaseChromosome MappingHaplotypesHomozygoteGenes, RecessiveJewsGenetic HeterogeneityGene FrequencyGenetic Diseases, InbornGenes, BRCA2Dystonia Musculorum DeformansMutation, MissenseFamilySyndromeGenetic MarkersHeterozygote DetectionCrosses, GeneticDystoniaBRCA2 ProteinAmyloid Neuropathies, FamilialGenetic CounselingGenetic VariationAngiomatosisHemochromatosisPolymorphism, Single NucleotideSyndactylyAbnormalities, MultipleLikelihood FunctionsProto-Oncogene Proteins c-retCraniofacial AbnormalitiesDNA, MitochondrialEpistasis, GeneticRetinoblastomaGenetics, MedicalChromosomes, Human, Pair 19RNA, Transfer, IleCardiomyopathy, Hypertrophic, FamilialBone Morphogenetic Protein Receptors, Type IIPrealbuminMyoclonusNeoplastic Syndromes, HereditaryInheritance PatternsBreast NeoplasmsMice, TransgenicOptic Atrophies, HereditaryExonsDystonic DisordersMice, Inbred C57BLRetinitis PigmentosaParaganglioma, Extra-AdrenalMicrosatellite RepeatsPoint MutationGenetic Association StudiesOvarian NeoplasmsEye Abnormalities
Variation in MAPT is not a contributing factor to the incomplete penetrance in LHON - ePrints - Newcastle UniversityVariation in MAPT is not a contributing factor to the incomplete penetrance in LHON - ePrints - Newcastle University
Wiley: A Statistical Approach to Genetic Epidemiology: Concepts and Applications, with an e-Learning Platform, 2nd Edition -...Wiley: A Statistical Approach to Genetic Epidemiology: Concepts and Applications, with an e-Learning Platform, 2nd Edition -...
Institute of Cancer Research Repository - Genetic Diagnosis of High-Penetrance Susceptibility for Colorectal Cancer (CRC) Is...Institute of Cancer Research Repository - Genetic Diagnosis of High-Penetrance Susceptibility for Colorectal Cancer (CRC) Is...
CRAN - Package FamEventCRAN - Package FamEvent
News | Rong Chen LabNews | Rong Chen Lab
VackvSuG: The alternative method; diss the two L-suicide beta-substratesVackvSuG: The alternative method; diss the two L-suicide beta-substrates
Penetrance - WikipediaPenetrance - Wikipedia
Penetrance vs ExpressivityPenetrance vs Expressivity
Penetrance?Penetrance?
tag/penetrance/tag/penetrance/
What are reduced penetrance and variable expressivity?: MedlinePlus GeneticsWhat are reduced penetrance and variable expressivity?: MedlinePlus Genetics
Penetrance dictionary definition | penetrance definedPenetrance dictionary definition | penetrance defined
Definition of Penetrance And Expressivity | Chegg.comDefinition of Penetrance And Expressivity | Chegg.com
Hemochromatosis--Genetic Prevalence and Penetrance - Full Text View - ClinicalTrials.govHemochromatosis--Genetic Prevalence and Penetrance - Full Text View - ClinicalTrials.gov
The penetrance of copy number variations for schizophrenia and developmental delay. - PubMed - NCBIThe penetrance of copy number variations for schizophrenia and developmental delay. - PubMed - NCBI
postnatal lethality, complete penetrance Mammalian Phenotype Term (MP:0011085)postnatal lethality, complete penetrance Mammalian Phenotype Term (MP:0011085)
Penetrance - wikidocPenetrance - wikidoc
Dr. Tuuli Lappalainen awarded major NIH grant to study variable penetrance | EurekAlert! Science NewsDr. Tuuli Lappalainen awarded major NIH grant to study variable penetrance | EurekAlert! Science News
Evaluation of LRRK2 G2019S penetrance: relevance for genetic counseling in Parkinson disease. - PubMed - NCBIEvaluation of LRRK2 G2019S penetrance: relevance for genetic counseling in Parkinson disease. - PubMed - NCBI
Analysis of KLLN as a high-penetrance breast cancer predisposition gene | SpringerLinkAnalysis of KLLN as a high-penetrance breast cancer predisposition gene | SpringerLink
Penetrance of Hypertrophic Cardiomyopathy in Children and AdolescentsClinical Perspective | CirculationPenetrance of Hypertrophic Cardiomyopathy in Children and AdolescentsClinical Perspective | Circulation
Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance |...Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance |...
PHG Foundation - Interactive Tutorial: Penetrance - IntroductionPHG Foundation - Interactive Tutorial: Penetrance - Introduction
Environmental Determinants of Expressivity and Penetrance in LRRK2 Parkinsonism | Parkinsons DiseaseEnvironmental Determinants of Expressivity and Penetrance in LRRK2 Parkinsonism | Parkinson's Disease
Genetic penetrance | definition of genetic penetrance by Medical dictionaryGenetic penetrance | definition of genetic penetrance by Medical dictionary
Retinal Electrophysiology Is a Viable Preclinical Biomarker for Drug Penetrance into the Central Nervous SystemRetinal Electrophysiology Is a Viable Preclinical Biomarker for Drug Penetrance into the Central Nervous System
Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinsons disease: a case-control studyPhenotype, genotype, and worldwide genetic penetrance of LRRK2-associated Parkinson's disease: a case-control study
Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled...Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled...
PLOS Genetics: Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast CancerPLOS Genetics: Common Genetic Variants and Modification of Penetrance of BRCA2-Associated Breast Cancer
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer | Cancer Epidemiology, Biomarkers & PreventionPrevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer | Cancer Epidemiology, Biomarkers & Prevention
A Novel Low-Penetrance Locus for Familial Glioma at 15q23-q26.3 | Cancer ResearchA Novel Low-Penetrance Locus for Familial Glioma at 15q23-q26.3 | Cancer Research
Haplogroup Context is Less Important in the Penetrance of Mitochondrial DNA Complex I Mutations Compared to mt-tRNA Mutations |...Haplogroup Context is Less Important in the Penetrance of Mitochondrial DNA Complex I Mutations Compared to mt-tRNA Mutations |...
Mosaicism and incomplete penetrance of PCDH19 mutations | Journal of Medical GeneticsMosaicism and incomplete penetrance of PCDH19 mutations | Journal of Medical Genetics
The survival gene MED4 explains low penetrance retinoblastoma in patients with large RB1 deletion. | Sigma-AldrichThe survival gene MED4 explains low penetrance retinoblastoma in patients with large RB1 deletion. | Sigma-Aldrich
MCC950 blocks enhanced interleukin-1β production in patients with NLRP3 low penetrance variants.MCC950 blocks enhanced interleukin-1β production in patients with NLRP3 low penetrance variants.
Parkin Exon Rearrangements and Sequence Variants in LRRK2 Mutations Carriers: Analysis on a Possible Modifier Effect on LRRK2...Parkin Exon Rearrangements and Sequence Variants in LRRK2 Mutations Carriers: Analysis on a Possible Modifier Effect on LRRK2...
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsAnthropology, Education, Sociology and Social PhenomenaNamed GroupsHealth Care
PenetrancePedigreeGenes, DominantHeterozygoteMutationPhenotypeGenetic LinkageGenetic Predisposition to DiseaseOptic Atrophy, Hereditary, LeberLod ScoreAllelesGerm-Line MutationFamily HealthGenotypeDNA Mutational AnalysisGenetic TestingGenes, BRCA1Genes, ModifierModels, GeneticAge of OnsetFounder EffectHirschsprung DiseaseChromosome MappingHaplotypesHomozygoteGenes, RecessiveJewsGenetic HeterogeneityGene FrequencyGenetic Diseases, InbornGenes, BRCA2Dystonia Musculorum DeformansMutation, MissenseFamilySyndromeGenetic MarkersHeterozygote DetectionCrosses, GeneticDystoniaBRCA2 ProteinAmyloid Neuropathies, FamilialGenetic CounselingGenetic VariationAngiomatosisHemochromatosisPolymorphism, Single NucleotideSyndactylyAbnormalities, MultipleLikelihood FunctionsProto-Oncogene Proteins c-retCraniofacial AbnormalitiesDNA, MitochondrialEpistasis, GeneticRetinoblastomaGenetics, MedicalChromosomes, Human, Pair 19RNA, Transfer, IleCardiomyopathy, Hypertrophic, FamilialBone Morphogenetic Protein Receptors, Type IIPrealbuminMyoclonusNeoplastic Syndromes, HereditaryInheritance PatternsBreast NeoplasmsMice, TransgenicOptic Atrophies, HereditaryExonsDystonic DisordersMice, Inbred C57BLRetinitis PigmentosaParaganglioma, Extra-AdrenalMicrosatellite RepeatsPoint MutationGenetic Association StudiesOvarian NeoplasmsEye Abnormalities
PedigreesPhenotypeExpressivityGenesHigh penetranceGeneEstimate the penetranceCommon low-penetrance allelesIncomplete or reduced penetranceFamilialAllelesMutation carriersPredispositionGenotypeAllelePrevalence and penetranceAutosomal dominant disorderDiseaseGermlineLower penetranceOverall penetranceHighly penetrantVariableInheritance patternHereditary hemochromatosisGenomeTumorsBreast cancerClinicalRetinoblastomaMaternalIndividualsMEN1PhenotypesCarriersEstimatesCorrelatesGenotypesCongenital glaucomaDefectsGenomicVariationModifiersVariabilityPopulations
Pedigrees1
  • Plot functions include pedigrees of simulated families and predicted penetrance curves based on specified parameter values. (ufpr.br)
Phenotype15
Expressivity16
Genes19
High penetrance1
Gene31
Estimate the penetrance4
Common low-penetrance alleles1
Incomplete or reduced penetrance3
Familial5
Alleles4
Mutation carriers7
Predisposition2
Genotype5
  • Penetrance is the probability that a person carrying a disease-associated genotype will develop the disease within a given time period. (phgfoundation.org)
  • A disease is said to show complete penetrance if a person carrying a disease associated genotype always develops the condition. (phgfoundation.org)
  • Cardiac penetrance was high in young asymptomatic LMNA genotype-positive family members with frequent AV block and VT, highlighting the importance of early family screening and cardiological follow-up. (uio.no)
  • For this population, we estimate that the penetrance of the HFE C282Y homozygous genotype, with respect to hepatocellular carcinoma, was between 1.31 % and 2.1% for males and was zero for females. (springer.com)
  • Maternal high-fat diet interacts with embryonic Cited2 genotype to reduce Pitx2c expression and enhance penetrance of left-right patterning defects. (ox.ac.uk)
Allele7
  • High and low penetrance: If an allele is highly penetrant, then the trait it produces will almost always be apparent in an individual carrying the allele. (wikipedia.org)
  • An allele with low penetrance will only occasionally produce the trait with which it is associated. (wikipedia.org)
  • Penetrance can be difficult to determine reliably, even for genetic diseases that are caused by a single polymorphic allele. (wikipedia.org)
  • Genome association studies may assess the influence of such variants on the penetrance of an allele. (wikipedia.org)
  • Determining the penetrance of the C282Y allele can be influenced when the medical community evaluates homozygotes. (wikipedia.org)
  • For example Huntingtons disease has 95% penetrance whereby 5% of those with the dominant allele for Huntingtons don't acquire the disease and 95% do. (wikidoc.org)
  • MAIN OUTCOME MEASURES: The penetrance of the variant rs74315329 was estimated from the percentage of the carriers of the risk allele of the variant who had high IOP (ocular hypertension) or glaucoma. (ru.nl)
Prevalence and penetrance1
Autosomal dominant disorder1
Disease25
  • In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms. (wikipedia.org)
  • A condition, most commonly inherited in an autosomal dominant manner, is said to show complete penetrance if clinical symptoms are present in all individuals who have the disease-causing mutation. (wikipedia.org)
  • For many hereditary diseases, the onset of symptoms is age related, and is affected by environmental factors such as nutrition and smoking, as well as genetic cofactors and epigenetic regulation of expression: Age-related cumulative frequency: Penetrance is often expressed as a frequency of disease at different ages. (wikipedia.org)
  • For hereditary hemochromatosis, a disease caused by excess intestinal iron absorption, the degree of penetrance has been a subject of controversy for many years and illustrates the challenges facing investigators seeking a quantitative measure of penetrance. (wikipedia.org)
  • The Lappalainen Lab will focus its research efforts on advancing scientific knowledge of a widely acknowledged but not well understood phenomenon called variable penetrance, where the severity of the effect of disease-causing variants differs among individuals who carry them. (eurekalert.org)
  • The Lappalainen Lab will examine the important implications of variable penetrance in human evolution and disease. (eurekalert.org)
  • This will be the first comprehensive work on characterizing how important this phenomenon is and how it can affect penetrance of disease-causing variants. (eurekalert.org)
  • Evaluation of LRRK2 G2019S penetrance: relevance for genetic counseling in Parkinson disease. (nih.gov)
  • We report the results of a family-based study of LRRK2 G2019S penetrance in Parkinson disease. (nih.gov)
  • If you were to think about it as an equation, penetrance is the number of individuals displaying clinical features of a condition, divided by the number of individuals with a disease-causing mutation, multiplied by 100. (phgfoundation.org)
  • Mitochondrial DNA variants that are linked to disease can exhibit variable expression and penetrance. (springer.com)
  • Studying haplogroup background and its impact on disease penetrance will help ensure similar levels of diagnostic accuracy to all populations (van der Walt et al. (springer.com)
  • This supports the theory that haplogroup background is important in the expression and penetrance of disease in humans. (springer.com)
  • Mutations in LRRK2 represent the most common causes of Parkinson's disease (PD) identified to date, but their penetrance is incomplete and probably due to the presence of other genetic or environmental factors required for development of the disease. (hindawi.com)
  • Macular telangiectasia (MacTel) is an adult-onset autosomal dominant disease with reduced penetrance. (arvojournals.org)
  • Partial penetrance can be viewed as nature's way of curing the disease. (ucl.ac.uk)
  • In this widely acknowledged but not well understood phenomenon, called variable penetrance, the severity of the effect of disease-causing variants differs among individuals who carry them. (technologynetworks.com)
  • Variable penetrance has long posed a challenge for predicting the severity of a disease, even for diseases with a strong genetic association. (technologynetworks.com)
  • They found an enrichment of combinations of regulatory and coding variants, called haplotypes, that act as protective against disease by decreasing the penetrance of coding variants associated with disease development. (technologynetworks.com)
  • Finally, they designed an experiment using CRISPR/Cas9 genome editing technology to test the modified penetrance hypothesis with a coding variant that is known to be associated with a disease. (technologynetworks.com)
  • This finding provides an important framework for scientists moving forward to experimentally test specific disease SNPs to determine if they could be affected by modified penetrance. (technologynetworks.com)
  • Now that we have demonstrated a mechanism for modified penetrance, the long-term goal of the research is better prediction of whether an individual is going to have a disease using their genetic data by integrating the regulatory and coding variants," Dr. Lappalainen said. (technologynetworks.com)
  • Genome-wide association studies have identified a number of common low-penetrance genetic variants, but their contribution to disease risk differs between populations. (biomedcentral.com)
  • Neither the highly variable penetrance of the optic neuropathy ─ which is always much greater in males ─ or the presence of extraocular signs can be exclusively explained by the presence of primary mutations that are necessary but not sufficient to cause the disease. (biomedcentral.com)
  • A woman at-risk for a rare fatal prion disease joined with a bioinformatics team to analyze shared data that provided insights about penetrance and treatment. (sciencemag.org)
Germline3
Lower penetrance1
  • Thus, our study suggests a much lower penetrance for rs74315329 for ocular hypertension (and thus glaucoma), in comparison with that reported previously. (ru.nl)
Overall penetrance3
  • We also estimate the strength of the selection pressure against CNVs and correlate this against their overall penetrance. (nih.gov)
  • Correlation between the overall penetrance and selection coefficients of CNVs. (nih.gov)
  • Results: The overall penetrance of PETs during the second decade of life was42%(8 of 19). (fapesp.br)
Highly penetrant1
Variable5
Inheritance pattern1
Hereditary hemochromatosis1
Genome1
  • The study links modified penetrance to specific diseases at the genome-wide level, which has exciting implications for future prediction of the severity of serious diseases such as cancer and autism spectrum disorder. (technologynetworks.com)
Tumors1
  • Context: Data are scarce on the penetrance of multiple endocrine neoplasia type 1 (MEN1)-related nonfunctioning pancreatic neuroendocrine tumors (NF-PETs) and insulinomas in young MEN1 patients. (fapesp.br)
Breast cancer1
Clinical3
  • We studied the penetrance of HCM and the short- and long-term outcomes of clinical screening and predictive genetic testing of child relatives of patients with HCM. (ahajournals.org)
  • Penetrance in this case can be defined as the frequency with which individuals of particular genotypes develop either iron overload or clinical manifestations. (springer.com)
  • My seminar will illustrate how clinical presentations and penetrance were just as challenging to the research that nominated those genetic targets, and will re-consider missed (future) opportunities. (reducedpenetranceconference.com)
Retinoblastoma2
Maternal2
  • To better understand the reduced penetrance and maternal penetrance bias associated with SCA8 we analyzed the sequence configurations and instability patterns of the CTG repeat in affected and unaffected family members. (biomedsearch.com)
  • Here we show that a maternal high-fat diet more than doubles the penetrance of laterality defects and, surprisingly, induces palatal clefting in Cited2-deficient embryos. (ox.ac.uk)
Individuals2
  • In the cancer patients and individuals with autism, they found an enrichment of haplotypes predicted to increase the penetrance of coding variants associated with cancer and autism spectrum disorder, respectively. (technologynetworks.com)
  • Additional documented symptoms include short-term memory loss, executive functional deficits, cognitive decline, parkinsonism, peripheral neuropathy, lower-limb proximal muscle weakness, and autonomic dysfunction.To study the penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) among premutation carriers.Family-based study of 192 individuals (premutation carriers and controls) whose families belong to the Northern or Southern California Fragile X Associations. (edu.au)
MEN11
Phenotypes2
Carriers1
  • We analyzed the presence of parkin sequence variants (mutations or polymorphisms) and exon rearrangements in LRRK2 mutations carriers (both PD patients and unaffected relatives) in order to detect a possible modifier effect on penetrance. (hindawi.com)
Estimates3
  • However, comparisons between their penetrance for SCZ or DD/ASD/CM, or estimates of the total penetrance for any of these disorders have not yet been made. (nih.gov)
  • The improved estimates of penetrance will provide crucial information for genetic counselling. (nih.gov)
  • This study provides accurate estimates of G2019S penetrance by minimizing the selection bias. (nih.gov)
Correlates2
Genotypes1
Congenital glaucoma1
Defects1
  • Our data indicate that Df1 /+ embryos are able to overcome a localized arterial growth impairment and thereby reduce the penetrance of birth defects. (oup.com)
Genomic1
Variation1
Modifiers1
  • Environmental modifiers: Penetrance may be affected by environmental factors. (wikipedia.org)
Variability1
Populations1
  • The frequency of the common LRRK2 Gly2019Ser mutation was estimated on the basis of data from 24 populations worldwide, and the penetrance of the mutation was defined in 1045 people with mutations in LRRK2 from 133 families. (nih.gov)
The genetics of prion diseases | Genetics in Medicine
The genetics of prion diseases | Genetics in Medicine (nature.com)
Von Willebrand disease | Genetics in Medicine
Von Willebrand disease | Genetics in Medicine (nature.com)
The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in...
The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in... (genetics.org)
Plus it
Plus it (clincancerres.aacrjournals.org)
December 2006 - Volume 27 - Issue 6 - Contributor Index : Ear and Hearing
December 2006 - Volume 27 - Issue 6 - Contributor Index : Ear and Hearing (journals.lww.com)
Frontiers | Genetic Predisposition to Solid Pediatric Cancers | Oncology
Frontiers | Genetic Predisposition to Solid Pediatric Cancers | Oncology (frontiersin.org)
4 March 2009 Media Release, News, University of Otago, New Zealand
4 March 2009 Media Release, News, University of Otago, New Zealand (otago.ac.nz)
Brian Dilkes - Mendeley
Brian Dilkes - Mendeley (mendeley.com)
Analysis of Human Genetic Linkage - Jurg Ott - Google Books
Analysis of Human Genetic Linkage - Jurg Ott - Google Books (books.google.com)
Analysis of KLLN as a high-penetrance breast cancer predisposition gene | SpringerLink
Analysis of KLLN as a high-penetrance breast cancer predisposition gene | SpringerLink (link.springer.com)
Table of Contents - January 20, 2016, 8 (322) | Science Translational Medicine
Table of Contents - January 20, 2016, 8 (322) | Science Translational Medicine (stm.sciencemag.org)
Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance |...
Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance |... (pnas.org)
The Genetic Bases of Cardiomyopathies | JACC: Journal of the American College of Cardiology
The Genetic Bases of Cardiomyopathies | JACC: Journal of the American College of Cardiology (onlinejacc.org)
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer | Cancer Epidemiology, Biomarkers & Prevention
Prevalence and Penetrance of Major Genes and Polygenes for Colorectal Cancer | Cancer Epidemiology, Biomarkers & Prevention (cebp.aacrjournals.org)
'alcian blue' Protocols and Video...
'alcian blue' Protocols and Video... (jove.com)
Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ )
Genetics of Kidney Cancer (Renal Cell Cancer) (PDQ ) (meb.uni-bonn.de)
The quack view of preventing cancer versus reality and Angelina Jolie, part 3 | ScienceBlogs
The quack view of preventing cancer versus reality and Angelina Jolie, part 3 | ScienceBlogs (scienceblogs.com)
5th Annual Early Age Onset Colorectal Cancer - Session V: Part I
5th Annual Early Age Onset Colorectal Cancer - Session V: Part I (slideshare.net)
Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled...
Analyses in zebrafish embryos reveal that nanotoxicity profiles are dependent on surface-functionalization controlled... (nature.com)
Perturbations of BMP/TGF-β and VEGF/VEGFR signalling pathways in non-syndromic sporadic brain arteriovenous malformations (BAVM...
Perturbations of BMP/TGF-β and VEGF/VEGFR signalling pathways in non-syndromic sporadic brain arteriovenous malformations (BAVM... (jmg.bmj.com)
Genetic Disorders: Penetrance & Phenotypic Variability - Video & Lesson Transcript | Study.com
Genetic Disorders: Penetrance & Phenotypic Variability - Video & Lesson Transcript | Study.com (study.com)
2 Evidence Considerations for Integrating Genomics-Based Programs into Health Care Systems | Implementing and Evaluating...
2 Evidence Considerations for Integrating Genomics-Based Programs into Health Care Systems | Implementing and Evaluating... (nap.edu)
3 Prevention and Early Detection | Ovarian Cancers: Evolving Paradigms in Research and Care | The National Academies Press
3 Prevention and Early Detection | Ovarian Cancers: Evolving Paradigms in Research and Care | The National Academies Press (nap.edu)
Familial Renal Amyloidosis: Background, Pathophysiology, Epidemiology
Familial Renal Amyloidosis: Background, Pathophysiology, Epidemiology (emedicine.medscape.com)
Penetrance vs Expressivity
Penetrance vs Expressivity (mun.ca)
A Pharmacokinetic Study to Characterize JNJ-39393406 in the Cerebrospinal Fluid of Healthy Volunteers - Full Text View -...
A Pharmacokinetic Study to Characterize JNJ-39393406 in the Cerebrospinal Fluid of Healthy Volunteers - Full Text View -... (clinicaltrials.gov)
A new paramutation-like example at the Delta gene of Drosophila
A new paramutation-like example at the Delta gene of Drosophila (journals.plos.org)
Gomez, A.P., Moreno, M.J., Baldrich, R.M. and Hernández, A. (2008) Endothelin-1 molecular ribonucleic acid expression in...
Gomez, A.P., Moreno, M.J., Baldrich, R.M. and Hernández, A. (2008) Endothelin-1 molecular ribonucleic acid expression in... (scirp.org)
ASAP Initiative | Parkinson's Disease
ASAP Initiative | Parkinson's Disease (michaeljfox.org)