An individual in which both alleles at a given locus are identical.

An individual having different alleles at one or more loci regarding a specific character.

The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.

The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.

Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.

The proportion of one particular in the total of all ALLELES for one genetic locus in a breeding POPULATION.

A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.

A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.

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)

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.

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

The genetic constitution of 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.

Identification of genetic carriers for a given trait.

Genotypic differences observed among individuals in a population.

Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.

Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.

Mice bearing mutant genes which are phenotypically expressed in the animals.

One of three major isoforms of apolipoprotein E. In humans, Apo E2 differs from APOLIPOPROTEIN E3 at one residue 158 where arginine is replaced by cysteine (R158--C). In contrast to Apo E3, Apo E2 displays extremely low binding affinity for LDL receptors (RECEPTORS, LDL) which mediate the internalization and catabolism of lipoprotein particles in liver cells. ApoE2 allelic homozygosity is associated with HYPERLIPOPROTEINEMIA TYPE III.

Genes that influence the PHENOTYPE only in the homozygous state.

Enzyme that catalyzes the movement of a methyl group from S-adenosylmethionone to a catechol or a catecholamine.

General term for a number of inherited defects of amino acid metabolism in which there is a deficiency or absence of pigment in the eyes, skin, or hair.

A group of familial disorders characterized by elevated circulating cholesterol contained in either LOW-DENSITY LIPOPROTEINS alone or also in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins).

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.

A flavoprotein amine oxidoreductase that catalyzes the reversible conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. This enzyme was formerly classified as EC 1.1.1.171.

In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.

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.

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.

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.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.

Individuals whose ancestral origins are in the southeastern and eastern areas of the Asian continent.

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.

Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone.

Individuals whose ancestral origins are in the continent of Europe.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.

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.

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)

Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.

Biochemical identification of mutational changes in a nucleotide sequence.

An autosomal recessively inherited disorder characterized by the accumulation of intermediate-density lipoprotein (IDL or broad-beta-lipoprotein). IDL has a CHOLESTEROL to TRIGLYCERIDES ratio greater than that of VERY-LOW-DENSITY LIPOPROTEINS. This disorder is due to mutation of APOLIPOPROTEINS E, a receptor-binding component of VLDL and CHYLOMICRONS, resulting in their reduced clearance and high plasma levels of both cholesterol and triglycerides.

An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).

The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.

Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.

Any method used for determining the location of and relative distances between genes on a chromosome.

The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.

Iron-containing proteins that are widely distributed in animals, plants, and microorganisms. Their major function is to store IRON in a nontoxic bioavailable form. Each ferritin molecule consists of ferric iron in a hollow protein shell (APOFERRITINS) made of 24 subunits of various sequences depending on the species and tissue types.

An autosomal recessive disorder caused by a deficiency of acid beta-glucosidase (GLUCOSYLCERAMIDASE) leading to intralysosomal accumulation of glycosylceramide mainly in cells of the MONONUCLEAR PHAGOCYTE SYSTEM. The characteristic Gaucher cells, glycosphingolipid-filled HISTIOCYTES, displace normal cells in BONE MARROW and visceral organs causing skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement.

A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.

Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.

A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.

An abnormal hemoglobin that results from the substitution of lysine for glutamic acid at position 26 of the beta chain. It is most frequently observed in southeast Asian populations.

Color of hair or fur.

Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.

A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.

A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia.

Enzymes catalyzing the dehydrogenation of secondary amines, introducing a C=N double bond as the primary reaction. In some cases this is later hydrolyzed.

An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.

Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.

Hemoglobins characterized by structural alterations within the molecule. The alteration can be either absence, addition or substitution of one or more amino acids in the globin part of the molecule at selected positions in the polypeptide chains.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

Structural proteins of the alpha-lipoproteins (HIGH DENSITY LIPOPROTEINS), including APOLIPOPROTEIN A-I and APOLIPOPROTEIN A-II. They can modulate the activity of LECITHIN CHOLESTEROL ACYLTRANSFERASE. These apolipoproteins are low in atherosclerotic patients. They are either absent or present in extremely low plasma concentration in TANGIER DISEASE.

DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.

The discipline studying genetic composition of populations and effects of factors such as GENETIC SELECTION, population size, MUTATION, migration, and GENETIC DRIFT on the frequencies of various GENOTYPES and PHENOTYPES using a variety of GENETIC TECHNIQUES.

Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.

Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.

A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.

The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases.

Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SEROTONIN UPTAKE INHIBITORS.

The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.

An iron-binding beta1-globulin that is synthesized in the LIVER and secreted into the blood. It plays a central role in the transport of IRON throughout the circulation. A variety of transferrin isoforms exist in humans, including some that are considered markers for specific disease states.

Color of the iris.

A peptidyl-dipeptidase that catalyzes the release of a C-terminal dipeptide, -Xaa-*-Xbb-Xcc, when neither Xaa nor Xbb is Pro. It is a Cl(-)-dependent, zinc glycoprotein that is generally membrane-bound and active at neutral pH. It may also have endopeptidase activity on some substrates. (From Enzyme Nomenclature, 1992) EC 3.4.15.1.

A major and the second most common isoform of apolipoprotein E. In humans, Apo E4 differs from APOLIPOPROTEIN E3 at only one residue 112 (cysteine is replaced by arginine), and exhibits a lower resistance to denaturation and greater propensity to form folded intermediates. Apo E4 is a risk factor for ALZHEIMER DISEASE and CARDIOVASCULAR DISEASES.

A 9-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS and CHYLOMICRON REMNANTS. Apo C-III, synthesized in the liver, is an inhibitor of LIPOPROTEIN LIPASE. Apo C-III modulates the binding of chylomicron remnants and VLDL to receptors (RECEPTORS, LDL) thus decreases the uptake of triglyceride-rich particles by the liver cells and subsequent degradation. The normal Apo C-III is glycosylated. There are several polymorphic forms with varying amounts of SIALIC ACID (Apo C-III-0, Apo C-III-1, and Apo C-III-2).

A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.

An increase in the total red cell mass of the blood. (Dorland, 27th ed)

A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).

Conditions with abnormally low levels of LIPOPROTEINS in the blood. This may involve any of the lipoprotein subclasses, including ALPHA-LIPOPROTEINS (high-density lipoproteins); BETA-LIPOPROTEINS (low-density lipoproteins); and PREBETA-LIPOPROTEINS (very-low-density lipoproteins).

A disorder characterized by reduced synthesis of the alpha chains of hemoglobin. The severity of this condition can vary from mild anemia to death, depending on the number of genes deleted.

The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.

Early pregnancy loss during the EMBRYO, MAMMALIAN stage of development. In the human, this period comprises the second through eighth week after fertilization.

A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.

Created 1 January 1993 as a result of the division of Czechoslovakia into the Czech Republic and Slovakia.

A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.

A species of fruit fly much used in genetics because of the large size of its chromosomes.

Mice which carry mutant genes for neurologic defects or abnormalities.

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.

The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome.

A benign familial disorder, transmitted as an autosomal dominant trait. It is characterized by low-grade chronic hyperbilirubinemia with considerable daily fluctuations of the bilirubin level.

A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.

Methods used to determine individuals' specific ALLELES or SNPS (single nucleotide polymorphisms).

An autosomal recessive genetic disease of the EXOCRINE GLANDS. It is caused by mutations in the gene encoding the CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR expressed in several organs including the LUNG, the PANCREAS, the BILIARY SYSTEM, and the SWEAT GLANDS. Cystic fibrosis is characterized by epithelial secretory dysfunction associated with ductal obstruction resulting in AIRWAY OBSTRUCTION; chronic RESPIRATORY INFECTIONS; PANCREATIC INSUFFICIENCY; maldigestion; salt depletion; and HEAT PROSTRATION.

Major structural proteins of triacylglycerol-rich LIPOPROTEINS. There are two forms, apolipoprotein B-100 and apolipoprotein B-48, both derived from a single gene. ApoB-100 expressed in the liver is found in low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). ApoB-48 expressed in the intestine is found in CHYLOMICRONS. They are important in the biosynthesis, transport, and metabolism of triacylglycerol-rich lipoproteins. Plasma Apo-B levels are high in atherosclerotic patients but non-detectable in ABETALIPOPROTEINEMIA.

A thiol-containing amino acid formed by a demethylation of METHIONINE.

The mating of plants or non-human animals which are closely related genetically.

A country spanning from central Asia to the Pacific Ocean.

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)

The most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. This protein serves as an acceptor for CHOLESTEROL released from cells thus promoting efflux of cholesterol to HDL then to the LIVER for excretion from the body (reverse cholesterol transport). It also acts as a cofactor for LECITHIN CHOLESTEROL ACYLTRANSFERASE that forms CHOLESTEROL ESTERS on the HDL particles. Mutations of this gene APOA1 cause HDL deficiency, such as in FAMILIAL ALPHA LIPOPROTEIN DEFICIENCY DISEASE and in some patients with TANGIER DISEASE.

Electrophoresis in which a starch gel (a mixture of amylose and amylopectin) is used as the diffusion medium.

A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships.

A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)

A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.

Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.

Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.

A group of inherited disorders characterized by structural alterations within the hemoglobin molecule.

A congenital anomaly of the hand or foot, marked by the presence of supernumerary digits.

A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and gamma-isomers have been characterized.

A group of apolipoproteins that can readily exchange among the various classes of lipoproteins (HDL; VLDL; CHYLOMICRONS). After lipolysis of TRIGLYCERIDES on VLDL and chylomicrons, Apo-C proteins are normally transferred to HDL. The subtypes can modulate remnant binding to receptors, LECITHIN CHOLESTEROL ACYLTRANSFERASE, or LIPOPROTEIN LIPASE.

A group of HEREDITARY AUTOINFLAMMATION DISEASES, characterized by recurrent fever, abdominal pain, headache, rash, PLEURISY; and ARTHRITIS. ORCHITIS; benign MENINGITIS; and AMYLOIDOSIS may also occur. Homozygous or compound heterozygous mutations in marenostrin gene result in autosomal recessive transmission; simple heterozygous, autosomal dominant form of the disease.

The major component of hemoglobin in the fetus. This HEMOGLOBIN has two alpha and two gamma polypeptide subunits in comparison to normal adult hemoglobin, which has two alpha and two beta polypeptide subunits. Fetal hemoglobin concentrations can be elevated (usually above 0.5%) in children and adults affected by LEUKEMIA and several types of ANEMIA.

Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.

Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol.

The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.

The influence of study results on the chances of publication and the tendency of investigators, reviewers, and editors to submit or accept manuscripts for publication based on the direction or strength of the study findings. Publication bias has an impact on the interpretation of clinical trials and meta-analyses. Bias can be minimized by insistence by editors on high-quality research, thorough literature reviews, acknowledgement of conflicts of interest, modification of peer review practices, etc.

Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.

A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.

Proteins that bind to and transfer CHOLESTEROL ESTERS between LIPOPROTEINS such as LOW-DENSITY LIPOPROTEINS and HIGH-DENSITY LIPOPROTEINS.

Congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy generally occurring between days 18-29 of gestation. Ectodermal and mesodermal malformations (mainly involving the skull and vertebrae) may occur as a result of defects of neural tube closure. (From Joynt, Clinical Neurology, 1992, Ch55, pp31-41)

Errors in the metabolism of LIPIDS resulting from inborn genetic MUTATIONS that are heritable.

Enzyme systems containing a single subunit and requiring only magnesium for endonucleolytic activity. The corresponding modification methylases are separate enzymes. The systems recognize specific short DNA sequences and cleave either within, or at a short specific distance from, the recognition sequence to give specific double-stranded fragments with terminal 5'-phosphates. Enzymes from different microorganisms with the same specificity are called isoschizomers. EC 3.1.21.4.

A 34-kDa glycosylated protein. A major and most common isoform of apolipoprotein E. Therefore, it is also known as apolipoprotein E (ApoE). In human, Apo E3 is a 299-amino acid protein with a cysteine at the 112 and an arginine at the 158 position. It is involved with the transport of TRIGLYCERIDES; PHOSPHOLIPIDS; CHOLESTEROL; and CHOLESTERYL ESTERS in and out of the cells.

The severe infantile form of inherited lysosomal lipid storage diseases due to deficiency of acid lipase (STEROL ESTERASE). It is characterized by the accumulation of neutral lipids, particularly CHOLESTEROL ESTERS in leukocytes, fibroblasts, and hepatocytes. It is also known as Wolman's xanthomatosis and is an allelic variant of CHOLESTEROL ESTER STORAGE DISEASE.

A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (POACEAE). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.

A form of pneumoconiosis resulting from inhalation of iron in the mining dust or welding fumes.

In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)

An autosomal recessively inherited disorder caused by mutation of LECITHIN CHOLESTEROL ACYLTRANSFERASE that facilitates the esterification of lipoprotein cholesterol and subsequent removal from peripheral tissues to the liver. This defect results in low HDL-cholesterol level in blood and accumulation of free cholesterol in tissue leading to a triad of CORNEAL OPACITY, hemolytic anemia (ANEMIA, HEMOLYTIC), and PROTEINURIA.

The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.

A chloride channel that regulates secretion in many exocrine tissues. Abnormalities in the CFTR gene have been shown to cause cystic fibrosis. (Hum Genet 1994;93(4):364-8)

Transport proteins that carry specific substances in the blood or across cell membranes.

A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable.

A system of universal human blood group isoantigens with many associated subgroups. The M and N traits are codominant and the S and s traits are probably very closely linked alleles, including the U antigen. This system is most frequently used in paternity studies.

Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.

The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.

RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.

Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease.

A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.

A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.

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.

Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.

Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.

Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.