ataxia-telangiectasia mutated (ATM)

27 Mar

ataxia-telangiectasia mutated (ATM)

ataxia-telangiectasia mutated (ATM) referring to a gene that has been mapped at 11q22.3 and is responsible for a rare neurological disorder. Ataxia refers to the unsteady gate of patients due to the death of certain of their brain cells. Dilated blood vessels called telangiectases develop on the surfaces of their eyes and facial skin. The functional allele en- codes a proetin that is a member of a family of phos- phatidylinositol-3-kinases, enzymes that respond to DNA damage by phosphorylating key substrates in- volved in DNA repair. See ATM kinase, DNA damage checkpoint, RAD. Atebrin a trade name for quinacrine (q.v.).

Also spelled Atabrine. ateliosis retarded growth resulting in a human of greatly reduced size but normal proportions. Such midgets generally show a marked deficiency in pitu- itary growth hormone. See pituitary dwarfism. (A T)/(G C) ratio the ratio between the num- ber of adenine-thymine pairs and the number of guanine-cytosine pairs in a given DNA sample. athenosphere See plate tectonics. ATM kinase a human DNA repair protein en- coded by the ataxia-telangiectasia mutated (ATM) gene (q.v.).

This enzyme plays a role in the DNA damage checkpoint (q.v.). See RAD. atom the smallest particle of an element that is ca- pable of undergoing a chemical reaction. See chemi- cal element. atomic mass the mass of a neutral atom of a nu- clide, usually expressed in terms of atomic mass units. atomic mass unit one-twelfth the weight of a 12C atom; equivalent to 1.67 × 10−24 g. atomic number the number of protons in the nu- cleus, or the number of positive charges on the nu- cleus: symbolized by Z. It also represents the num- ber of orbital electrons surrounding the nucleus of a neutral atom. atomic weight the weighted mean of the masses of the neutral atoms of an element expressed in atomic weight units. ATP adenosine triphosphate. See adenosine phos- phate.

ATPase any enzyme capable of hydrolyzing a phosphate bond in ATP. The energy derived from the hydrolysis is often used directly for transport of ions through membranes or for mechanical work. See adenosine phosphate, Wilson disease (WD). ATP7B gene a gene located on the long arm of hu- man chromosome 13 in region 14.2-21. It encodes an enzyme called copper transporting ATPase 2. This molecule belongs to a family of enzymes that trans- port metals in and out of cells using ATP as an en- ergy source. See adenosine phosphate, ATPase, Wil- son disease (WD). ATP synthase a multimeric protein complex that plays a key role in the energy metabolism of all or- ganisms. The inner membranes of the mitochondria of eukaryotes are covered with these organelles. They appear as particles 8-9 nm in diameter. Each particle has a spherical head piece (the F1 domain) that projects into the matrix of the mitochondrion and contains the catalytic sites for ATP synthesis.

Imbedded in the lipid bilayer that forms the inner membrane of the mitochondrion is a cylindrical hy- drophobic tailpiece (the Fo domain) that contains a channel for a stream of protons. This powers a rota- tion generator which is made up of a ring of 10-12 subunits that rotate 50-100 times a second. This ro- tation force is mechanically coupled to the catalytic sites in the F1 domain. These undergo a cycle of conformational changes which first loosely bind ATP and inorganic phosphate molecules, then rigidly bind the nascent ATP, and finally release it. To- gether the components of the different domains of ATP synthase contain at least 16 different proteins, and many mutations have been detected in the genes in the nuclei which encode these. Such loss of func- tion mutations are generally lethal when hemizygous or homozygous. There are also two genes located in mtDNA, and individuals with mutations in their mt- DNA can survive, provided wild-type mitochondria are also present in their cells.

The ATP synthases of bacteria and chloroplasts resemble those of mito- chondria with respect to the proteins that occupy the Fo and F1 domains. In bacteria, eight of the genes that encode these proteins are clustered in a single operon. See Appendix C, 1973, Boyer; 1981, Walker; adenosine phosphate, chemiosmotic theory, heteroplasmy, Leigh syndrome. atresia congenital absence of a normal passageway. Absence of a normally open lumen. atrichia hairlessness. In the domestic dog, the con- dition is inherited as an autosomal dominant. Homo- zygotes are stillborn. attached X chromosome monocentric elements containing two doses of the X chromosome. Drosoph- ila females carrying attached X chromosomes usually also have a Y chromosome. They produce XX and Y eggs and therefore generate patroclinous sons (which inherit their X from their father and their Y from their mother) and matroclinous daughters (which inherit their X from their mother and their Y from their fa- ther).

The terms double X and compound X are also used for aberrant chromosomes of this types. See Ap- pendix C, 1922, Morgan; detached X. attachment efficiency See seeding efficiency. attachment point (ap) a hypothetical analog of the centromere on chloroplast DNA in Chlamydo- monas. Chloroplast genes may be mapped with re- spect to the attachment point. attenuation 1. in physics, the loss in energy of an electromagnetic radiation as it passes through mat- ter. 2. in microbiology, the loss in virulence of a pathogenic organism as it is repeatedly subcultured or is let multiply on unnatural hosts. 3. in immunol- ogy, the reduction in virulence of a substance to be used as an immunogen.

Attenuation may result from aging, heating, drying, or chemically modifying the immunogen. 4. in molecular genetics, a mechanism for regulating the expression of bacterial operons that encode enzymes involved in amino acid biosyn- thesis. See attenuator. attenuator a nucleotide sequence that is located upstream of those bacterial operons which encode the enzymes that are involved in the synthesis of amino acids. The expression of such operons is switched on and off by controlling the transcription of the messages for these operons. The leader se- quence of the tryptophan operon of E. coli illustrates how attenuators function. In drawing A, an RNA polymerase is moving along the coding strand of a bacterial DNA molecule. The RNA molecule tran- scribed by the polymerase dangles behind it. Near its 5′ end is a site for binding ribosomes. One has attached and is moving along the RNA, forming a polypeptide as it goes.

How fast the ribosome moves is determined by the availability of amino acid- charged tRNAs. The detailed structure of the RNA transcript is illustrated here in drawing B. The blocks designated A and B can pair because their base se- quences are complementary and so can C and D. However, B can also pair with C, so there are three hairpin loops that can form, A/B, B/C, C/D. How- ever, only the A segment contains tryptophan co- dons (symbolized by Xs). When tryptophan is abun- dant, the ribosome moves without pause past A to B. As the polymerase transcribes C and D, these pair to form a termination hairpin (q.v.), and the RNA polymerase together with its transcript detach from the DNA strand. Therefore, the trp operon is si- lenced. However, when there is no tryptophan in the environment, the ribosome pauses at the trp co- dons. Since A is covered by the ribosome, B pairs with C, and now D cannot form a termination hair- pin.

Therefore, the polymerase continues to the op- eron and transcribes it. The transcript is later trans- lated, and the enzymes that result catalyze the formation of tryptophan. Thus, enzymes required for making an essential amino acid are synthesized only when the amino acid is scarce. See Appendix C, 1977, Lee and Yanofsky; leader sequence. $

att sites loci on a phage and the chromosome of its bacterial host where recombination integrates the phage into or excises it from the bacterial chromo- some. audiogenic seizure convulsions induced by sound. Certain strains of mice, rats, and rabbits are espe- cially prone to such seizures. aureomycin See tetracycline. Australian one of the six primary biogeographic realms (q.v.), comprising Australia, the Celebes, New Guinea, Tasmania, New Zealand, and the oce- anic islands of the South Pacific. Australopithecine referring to early hominids, fossils of which have been found in Africa.

Accord- ing to some classifications, the genus Australopith- ecus contains four species: A. afarensis, A. africanus, A. robustus, and A. boisei, all of which lived between 4 and 1 million years ago. The famous fossil “Lucy” is a 40% complete skeleton found in 1977. She lived about 3 million years ago and belonged to A. afaren- sis. autapomorphic character 1. a derived character evolved from a plesiomorphic character state in the immediate ancestor of a single species 2. uniquely derived characters shared by several synapomor- phous taxa.

For example, hair was an autapomorphy of the first mammalian species and is also a synapo- morphy of all mammals. autarchic genes in mosaic organisms, genes that are not prevented from manifesting their phenotypic effects by gene products diffusing from genetically different neighboring tissues, whereas hyparchic genes are so inhibited. autism a psychiatric disorder that usually is mani- fested by 3 years of age.

The child shows an im- paired ability to interact socially by eye-to-eye gaze, facial expression, body posture, and gestures. Spo- ken language either never develops or is delayed, and the child exhibits repetitive patterns of behavioral interests and activities and an abnormal preoccupa- tion with routines. The prevalence in the U.S. popu- lation is 4 in 10,000, with a male-to-female ratio of 4:1. Susceptibilityto autism iscaused by genesat a variety of sites on autosomes 2, 6, 7, 13, 15, and the X. The most common chromosomal aberration causing autism is a maternally inherited duplication in the region 15q11-13. autocatalysis the promotion of a reaction by its product. See protein splicing, ribozyme. autochthonous pertaining to a species that has evolved within the region where it is native. autocrine descriptive of a substance (e.g., a cyto- kine, q.v.) that binds to a surface receptor of the same cell that secreted it.

Paracrine action is the binding of a secreted substance to a receptor on a nearby cell. Endocrine action is the binding of a se- creted substance to a receptor on a distant cell. See agouti. autofertilization See thelytoky. autogamy that mode of reproduction in which the zygote is formed by fusion of two haploid nuclei from the same individual. In Paramecium, a process of self-fertilization resulting in homozygosis. In sin- gle individuals, the two micronuclei each undergo meiosis and seven of the eight resulting nuclei de- generate. The remaining haploid nucleus divides mi- totically and the two identical nuclei fuse.

The fu- sion nucleus gives rise to the micro- and macronuclei of the paramecium and its progeny. Autogamy is therefore a mode of nuclear reorganization that con- stitutes an extreme form of inbreeding. In P. aurelia, autogamy occurs spontaneously at regular intervals. autogenous insect species in which females can produce eggs without first feeding.

See anautoge- nous insect. autogenous control regulation of gene expression by its own product either inhibiting (negative autog- enous control) or enhancing (positive autogenous control) its activity. For example, in E. coli, AraC protein (the regulatory factor for the arabinose op- eron) controls its own synthesis by binding to the AraC promoter. autograft the transplantation of a living piece of tissue from one site to another on the same animal. autoimmune disease any pathological condition resulting from an individual’s immune response to its own cells or tissues.

See AIDS, arthritis, lupus ery- thematosus. autologous referring to a graft from one region to another on the same animal. automimic a palatable individual that is an auto- matic mimic of members of the same species that are unpalatable to predators. See automimicry. automimicry the phenomenon, seen for example in the Monarch butterfly (q.v.), in which the species has a polymorphism in terms of its palatability to predators.

The polymorphism arises from the differ- ent food plants chosen by the ovipositing female. Most members of the species are rendered unpalat- able because they feed as larvae upon plant species rich in substances toxic to birds. Those insects that feed on plants containing no toxins are palatable.

However, such insects mimic perfectly the more abundant, unpalatable members of the species. See mimicry. automixis fusion of nuclei or cells derived from the same parent to yield homozygous offspring. An example would be autogamy in paramecia or auto- mictic parthenogenesis, as seen in certain species of Lepidoptera. See autogamy, thelytoky. automutagen any mutagenic chemical formed as a metabolic product by an organism. autonomous controlling element a controlling el- ement (q.v.), apparently having both receptor and regulator functions, that enters a gene and makes it an unstable mutant. autonomously replicating sequences eukaryotic DNA sequences that function as origins of replica- tion, even though all of them may not be used in every cell cycle. ARSs have been isolated in yeast, and their functioning requires a 14 base pair core region. This contains an 11 base pair consensus se- quence that consists almost entirely of A-T base pairs.

See replication origin, replicon. autophagic vacuole an enlarged lysosome con- taining mitochondria and other cellular organelles in the process of being digested. autophene a phenotype due to the genetic consti- tution of the cells showing it. Transplantation of such mutant cells to a wild-type host does not mod- ify their mutant phenotype. autopoiesis the ability of an organism to maintain itself through its own metabolic processes at the ex- pense of carbon and energy sources. Cells are auto- poietic; viruses and plasmids are not. autopolyploid a polyploid that originates by the multiplication of one basic set of chromosomes.

See autotetraploid. autoradiograph a photographic picture showing the position of radioactive substances in tissues, ob- tained by coating a squash preparation or a section with a photographic emulsion in the dark, and sub- sequently developing the latent image produced by the decay radiations. In the case of colony hybridiza- tion (q.v.), a filter containing the radioactive chimeric vectors is taken to a dark room, placed in an x-ray film holder, and covered with a sheet of x-ray film. The film is then left to expose for several hours or a few days before it is processed.

The position of the silver grains on the film marks the location of the col- onies of interest. See also DNA fiber autoradiography. autoradiographic efficiency the number of acti- vated silver grains (produced in a photographic emulsion coating a section) per 100 radioactive dis- integrations occurring within the tissue section dur- ing the exposure interval. autoradiography a technique for localizing radio- actively labeled molecules by applying a photosensi- tive emulsion to the surface of a radioactive speci- men. See autoradiograph. autoregulation regulation of the synthesis of a gene product by the product itself. In the simplist autore- gulated systems, excess gene product behaves as a repressor and binds to the operator locus of its own structural gene.

Contrast with end product inhibition. autoselection the process whereby a genetic ele- ment tends to increase in frequency by virtue of the nature of its transmission, even though it has no ef- fect on the viability, fecundity, or fertility of the in- dividual that bears it. autosexing the use of sex-linked genes with obvi- ous phenotypic effects to permit the identification by external inspection of the sex of immature organ- isms (larval silkworms or chicks, for example) before sexual dimorphic traits become obvious. autosome any chromosome other than a sex chro- mosome.

Each diploid organism will have a set of autosomes contributed by the male and a set con- tributed by the female parent. Therefore, there will be a maternal and a paternal representative of auto- somes 1, 2, . . . n. The genes residing on autosomes follow the mode of distribution of these chromo- somes to the gametes during meiosis. This pattern (autosomal inheritance) differs from that of genes on the X or Y chromosomes, which show the sex- linked mode of inheritance.

See chromosome set, hu- man pseudoautosomal region, sex linkage. autosyndesis See allosyndesis. autotetraploid an autopolyploid with four similar genomes. If a given gene exists in two allelic forms A and a, then five genotypic classes can be formed in an autotetraploid: AAAA (quadruplex), AAAa (triplex), AAaa (duplex), Aaaa (simplex), and aaaa (nulliplex). autotrophs organisms that can build their own macromolecules from very simple, inorganic mole- cules, such as ammonia and carbon dioxide. Auto- trophs include photosynthetic bacteria, protoctist.

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