Myotonic dystrophy

31 Mar

Myotonic dystrophy
nome. The related species M. pneumoniae has a larger genome (820 kb), and the number of ORFs is 679. All 470 ORFs from the smaller species are found in the larger bacterium, and their protein se- quences are 67% identical. See Appendix A, Prokary- otae, Aphragmabacteria; Appendix C, 1985, Yamao; 1995, Fraser, Venter et al.; Appendix E; bacterial cell wall, pleuropneumonia-like organisms, TIGR, univer- sal code theory. Mycostatin a trade name for nystatin (q.v.).

myelin sheath the insulating covering of an axon formed by the plasma membrane of a Schwann cell. myeloblasts cells that differentiate by aggregation to form multinucleated, striated muscle cells. myeloid leukemia See Philadelphia (Ph1) chromo- some. myeloma cancer of plasma cells, presumably due to clonal proliferation of a single plasma cell that es- capes the normal control of division. Such cells re- produce and secrete a specific homogeneous protein related to gamma globulins. See Bence-Jones pro- teins, HAT medium, hybridoma. myeloma protein a partial or complete immuno- globulin molecule secreted by a myeloma (q.v.). myeloproliferative disease any disease caused by the uncontrolled proliferation of blood cells pro- duced in the bone marrow.

Leukemias result from proliferating lymphocytes. Lymphomas also contain proliferating lymphocytes, but in this case the sources are lymph nodes. Granulocytes, monocytes, and megakaryocytes (all of which see) are the sources of myeloid leukemias. The designation “acute” indi- cates that the cancer cells remain immature, divide rapidly, and are destined to overwhelm the body; whereas the “chronic” term is used for cells that di- vide less frequently and mature enough to perform some of their normal functions. See Abelson murine leukemia virus, acute myeloid leukemia 1 gene, Bur- kitt lymphoma, Philadelphia (Ph1) chromosome, poly- cythemia. Myleran a trade name for busulfan (q.v.). myoglobin the monomeric heme (q.v.) protein that stores oxygen in vertebrate muscles. The myo- globin gene is thought to have been derived directly from the ancestral gene that by duplication pro- duced an ORF that evolved into the alpha chain gene of hemoglobin (q.v.).

The myoglobin and alpha chain genes diverged 600 to 800 million years ago. Human myoglobin contains 152 amino acids. See Appendix C, 1958, Kendrew et al.; gene superfamily, hemoglobin genes. myoglobin gene the gene that encodes myoglo- bin.

It is remarkable in that less than 5% of its struc- ture codes for message. All the genes of the alpha and beta hemoglobin families are made up of three coding regions interrupted by two introns. The myo- globin gene contains four exons and three introns, and each of these introns is much longer than any of those found in hemoglobin genes. myosin the hexameric protein that interacts with actin (q.v.) to convert the energy from the hydrolysis of ATP into the force for muscle contraction. Actin functions both as a structural protein and an en- zyme. A myosin molecule can catalyze the hydroly- sis of 5 to 10 ATP molecules per second.

Each myo- sin consists of a slender stem (about 135 nanometers long) and a globular head region (about 10 nanome- ters long). The molecule is formed from two identi- cal heavy chains, each possessing about 2,000 amino acids. In the tail region, the heavy chains twist to- gether to form an alpha helix, from which the two globular heads protrude. The C termini are distal to the heads. Two light chain proteins, A1 (190 amino acids) and A2 (148 amino acids), attach to the globu- lar heads of each heavy chain. The light chain pro- teins contain calcium-binding sites. The globular head regions contain the ATPase activity and can bind temporarily to actin to form a complex referred to as actomyosin. In avian and mammalian species, numerous isoforms of both myosin heavy and light chains have been isolated from muscle and nonmus- cle tissues. myosin genes the genes encoding the isoforms of the heavy and light myosin chains. In Drosophila, two myosin heavy chain genes have been identified: one encoding a muscle myosin (Mhc) and one en- coding a cytoplasmic myosin (Mhc-c). The transcrip- tion unit of Mhc is 22 kilobases long and contains 19 different exons. Multiple transcripts are generated by alternative splicing (q.v.).

Genes for the two light chains are also known. In mammals, the muscle my- osin heavy chain isoforms are encoded by a family containing at least 10 genes. myotonic dystrophy an autosomal dominant dis- order due to an unstable trinucleotide repeat (q.v.). The gene involved encodes a muscle protein kinase, and the trinucleotide repeat is located in the 3′ un- translated region of the gene. In susceptible families, there is an increase in the severity of the disease in successive generations. See genetic anticipation.

myria a rarely used prefix meaning 10,000. Used with metric units of measurement. myriapod an arthropod belonging to the Myria- poda. Millipedes and centipedes were the first animals to colonize the land. See Appendix A, Ar- thropoda, Mandibulata, Myriapoda; metamerism, Si- lurian. Mytilus edulis See Pelecypoda. myxomatosis a fatal virus disease affecting rabbits. The virus was introduced into wild populations of rabbits in Australia as a means of controlling them. Myxomycota the phylum containing the plasmo- dial slime molds. These protoctists generate multi- nucleate plasmodia that feed by phagocytosis and subsequently form stalked, funguslike fruiting struc- tures. From the standpoint of genetics, Physarum po- lycephalum is the best-known species.

n neutron (q.v.). N 1. the haploid chromosome number. 2. normal solution. 3. nitrogen. N-acetyl serine an acetylated serine thought to function in mammalian systems as N-formylmethio- nine does in bacterial translation.

NAD nicotinamide-adenine dinucleotide (q.v.). NADP nicotinamide-adenine dinucleotide phos- phate (q.v.). Naegleria a genus of soil amoebas capable of transforming into flagellates. Species from this genus are often studied in terms of the morphogenesis of flagella. nail patella syndrome a hereditary disease in hu- mans. Individuals afflicted with this disorder have misshapen fingernails and small kneecaps, or lack them. The disease is due to a dominant gene residing on chromosome 9. nalidixic acid an antibiotic that inhibits DNA rep- lication in growing bacteria. It specifically inhibits the DNA gyrase of E. coli.

nanometer (nm) one-billionth (10−9) meter. The preferred length unit for describing ultrastructural dimensions (e.g., a ribosome of 15 nm diameter). The nanometer replaces the millimicron (mµ), an equivalent length, found in the earlier literature. Ten nm equals one Angstrom unit. nanos (nos) a Drosophila gene that maps to 3- 66.2, and it encodes an RNA-binding protein that blocks translation. This repressor is localized at the posterior pole of embryos where it functions to shut down the translation of mRNAs produced by hunch- back (q.v.). narrow heritability See heritability.

nascent polypeptide chain the forming polypep- tide chain that is attached to the 50 S subunit of a ribosome through a molecule of tRNA. The free end of the nascent polypeptide contains the N-terminal amino acid. See translation. nascent RNA an RNA molecule in the process of being synthesized (hence incomplete) or a complete, newly synthesized RNA molecule before any alter- ations have been made (e.g., prior to nuclear pro- cessing or RNA editing, both of which see). Nasonia brevicornis another name for Mormon- iella vitripennis (q.v.). Nasonia vitripennis another name for Mormon- iella vitripennis (q.v.). native indigenous.

A native species is not intro- duced into an area by humans, either intentionally or accidentally. natural immunity an outmoded concept that some immunities are inherited in the apparent absence of prior contact with an antigen. The prevailing para- digm is that all immunity ultimately requires contact with a sensitizing antigen and therefore is acquired. natural killer (NK) cells large leukocytes found in the blood (where they make up about 10% of the total lymphocytes) and in spleen and lymph nodes. They are activated by interferon (q.v.), and they at- tack tumor cells without prior immunization. NK cells are distinct from B lymphocytes and T lympho- cytes. natural selection the differential fecundity (q.v.) in nature between members of a species possessing adaptive characters and those without such advan- tages. See Appendix C, 1818, Wells; 1858, Darwin and Wallace; 1859, Darwin; 1934, 1937, L’He´ritier and Teissier; 1952, Bradshaw; 1954, Allison; artifi- cial selection, evolution, fundamental theorem of nat- ural selection, heavy metals, selection.

Nautilus

Nautilus See living fossil. nD refractive index. Ndj 1 See bouquet configuration. Neandertal a race of humans that roamed through Europe, North Africa, the Near East, Iraq, and Cen- tral Asia in the middle and upper Pleistocene (300,000 to 30,000 years ago). The fossils are named after the valley in western Germany where they were first discovered. The ranges of Homo neandertalensis and Homo sapiens overlapped in Europe during re- cent millennia, but there seems to have been little interbreeding. Sequence comparisons of the D loop (q.v.) region of mtDNA from Neandertal fossilized bones and modern humans show that Neandertals became extinct without leaving a trace of their mtDNAs in modern humans. See Appendix C, 1997, Krings et al., Homo. Nearctic one of the six biogeographic realms (q.v.) of the earth, comprising North America, Greenland, and extending to the Mexican plateau. nebenkern a two-stranded helical structure sur- rounding the proximal region of the tail filament of a spermatozoon. The nebenkern is derived from clumped mitochondria. negative complementation suppression of the wild-type activity of one subunit of a multimeric protein by a mutant allelic subunit. negative contrast technique See negative stain- ing.

negative eugenics See eugenics. negative feedback the suppression or diminution of an effect by its own influence on the process that gives rise to it. negative gene control prevention of gene expres- sion by the binding of a specific controlling factor to DNA. For example, in bacterial operons (either inducible or repressible), the binding of a repressor protein to the operator prevents transcription of structural genes in that operon. See regulator gene. Compare with positive gene control. negative interference a situation in which the co- efficient of coincidence is greater than 1. In such cases, the occurrence of one exchange between ho- mologous chromosomes appears to increase the like- lihood of another in its vicinity. negative regulation See negative gene control. negative sense ssDNA or RNA See plus (+) and minus (−) viral strands. negative staining a staining technique for high- resolution electron microscopy of viruses.

A virus suspension is mixed with a phosphotungstic acid so- lution and poured into an atomizer sprayer. The mixture is then sprayed upon electron microscope grids previously coated with a film of carbon. The phosphotungstic acid enters the contours of the specimen, which is viewed as a light object against a dark background. See Appendix C, 1959, Brenner and Horne. negative supercoiling See supercoiling. neobiogenesis the concept that life has been gen- erated from inorganic material repeatedly in nature. neo-Darwinism the post-Darwinian concept that species evolve by the natural selection of adaptive phenotypes caused by mutant genes. Neogene a subdivision of the Tertiary period, in- corporating the Pliocene and Miocene epochs.

See geologic time divisions. Neolithic pertaining to the later Stone Age, during which agriculture and animal husbandry originated and flourished. neomorph a mutant gene producing a qualita- tively new effect that is not produced by the normal allele. neomycin an antibiotic produced by Streptomyces fradiae. neontology the study of living (extant) species, as opposed to paleontology (the study of extinct spe- cies). neoplasm a localized population of proliferating cells in an animal that are not governed by the usual limitations of normal growth. The neoplasm is said to be benign if it does not undergo metastasis and malignant if it undergoes metastasis. neotenin synonym for allatum hormone (q.v.). neoteny the retention of larval characteristics throughout life with reproduction occurring during the larval period. In Ambystoma mexicanum, for ex- ample, the gill-breathing, water-dwelling larval sala- mander matures and reproduces sexually without undergoing metamorphosis to a lung-breathing, land- dwelling, adult form. See axolotl. Neotropical one of the six biogeographic realms (q.v.) of the earth, comprising Central and South America (south of the Mexican plateau) and the West Indies.

Neurosecretory spheres

neuraminic acid a nine-carbon amino sugar widely distributed in living organisms. One of the distinc- tions between eubacteria and archaebacteria is the presence of neuraminic acid in the cell walls of the former and its absence in the latter. In animals, neu- raminic acid is found in mucolipids, mucopolysac- charides, and glycoproteins. Neuraminic acid-con- taining membrane components play a role in the attachment and penetration of virus particles into animal cells. See ganglioside.

neuregulins (NRGs) a family of structurally re- lated growth and differentiation factors found in the central and peripheral nervous systems, which in- cludes products of the Nrg1, Nrg2, Nrg3, and Nrg4 genes. NRG1, the most widely studied neuregulin, has 14 different isoforms, produced by alternative splicing of its mRNA, and 7 isoforms of NRG2 have been identified. A variety of proteins identified in various independent studies, including the neu dif- ferentiation factor (NDF), heregulin (HRG), glial growth factor 2 (GGF2), and acetylcholine recep- tor-inducing activity (ARIA), are all isoforms of NRG1, produced by alternatively spliced mRNA.

All NRG1 isoforms have in common with each other and with other neuregulins an epidermal growth factor (EGF)-like sequence, which is essen- tial for their function. Some neuregulins have in common a transmembrane domain, followed by a variable intracellular domain, while others differ from one another in their N-terminal domains. These structural features suggest functional similari- ties as well as distinctions between the neuregulin family members.

NRGs interact with a family of re- ceptor tyrosine kinases on target cells to influence a number of cellular processes, including the synthesis of acetylcholine receptors at neuromuscular junc- tions, the proliferation and survival of oligodendro- cytes, and the proliferation and myelination of Schwann cells. Nrg1 is a candidate gene for schizo- phrenia (q.v.) and is also thought to be linked to age- related memory loss. See epidermal growth factor (EGF). neurofibroma a fibrous tumor of peripheral nerves. neurofibromatosis one of the most common sin- gle gene disorders affecting the human nervous sys- tem. The disease is characterized by the presence in the skin, or along the course of peripheral nerves, of multiple neurofibromas that gradually increase in number and size.

There are two types of neurofi- bromatosis, abbreviated NF1 and NF2. NF1 (also called von Recklinghausen disease) is one of the most common autosomal dominant disorders of hu- mans, affecting 1/3,000 individuals. The NF1 gene is located on the long arm of chromosome 17 at 11.2. The gene spans 3 × 105 nucleotides and en- codes a protein (neurofibromin) containing 2,818 amino acids. The spontaneous mutation rate of the NF1 gene is high, and 30-50% of patients carry new NF1 mutations. Neurofibromatosis 2 is a rarer con- dition, affecting about 1 in 37,000 individuals. The NF2 gene is at 22q12, and it encodes a protein (mer- lin) containing 590 amino acids. Neurofibromin is located in the cytoplasm and apparently functions in signal transduction (q.v.), whereas merlin is believed to link the cell membrane to certain cytoskeletal proteins.

See anti-oncogenes. http://www.nf.org neurofibromin See neurofibromatosis. neurohormone a hormone synthesized and se- creted by specialized nerve cells; e.g., gonadotropin- releasing hormone produced by neurosecretory cells located in the hypothalamus. neurohypophysis the portion of the hypophysis that develops from the floor of the diencephalon. neurological mutant a mutant producing malfor- mations of the sense organs or the central nervous system or striking abnormalities in locomotion or behavior. Hundreds of neurological mutants have been collected in Drosophila, Caenorhabditis, and the mouse.

See Appendix C, 1969, Hotta and Benzer; 1971, Suzuki et al.; 1981, Chalfie and Sulston; 1986, Tomlinson and Ready. neuron a nerve cell. neuropathy a collective term for a great variety of behavioral disorders that may have hereditary com- ponents. neurosecretory spheres electron-dense spheres 0.1-0.2 micrometers in diameter, synthesized by and transported in the axoplasm of specialized neu- rons.

Neurospora crassa
Neurospora crassa the ascomycete fungus upon which many of the classical studies of biochemical genetics were performed. In Neurospora each set of meiotic products is arranged in a linear fashion, and therefore the particular meiotic division at which genetic exchange occurs can be determined by dis- secting open the ascus and growing the individual ascospores (see ordered tetrad). The haploid chro- mosome number of this species is 7, and seven de- tailed linkage maps are available. Neurospora is esti- mated to have a genome of 38.6 million nucleotide base pairs.

It has around 10,000 genes, but only about 1,400 have counterparts in Drosophila, Caeno- rhabditis, or humans. More than half of its genes have no similarity to those in the other fungi that have been sequenced (Saccharomyces and Schizosac- charomyces). There are about 1.7 introns per gene, with an average intron size of 134 nucleotides.

Neu- rospora has a lower proportion of genes in multigene families than any other species for which data are available. This is because it has evolved repeat-in- duced point mutation (RIP) (q.v.), a mechanism for detecting and mutationally inactivating DNA dupli- cations. Dispersed throughout the genome are 424 tRNA genes and 74 5S rRNA genes. There are also 175-200 copies of a tandem repeat that contains the 17S, 5.8S, and the 25S rRNA genes. These are local- ized in the nucleolus organizer which somehow pro- tects them from RIP. The Neurospora mitochondrial DNA contains 60,000 nucleotide pairs. See Appen- dix A, Fungi, Ascomycota; Appendix C, 1927, Dodge; 1941, Beadle and Tatum; 1944, Tatum et al.; 1948, Mitchell and Lein; 2003, Galagan et al.; Appendix E; Appendix F. neurula the stage of development of a vertebrate embryo at which the neural axis is fully formed and histogenesis is proceeding rapidly. neutral equilibrium See passive equilibrium. neutral mutation 1. a genetic alteration whose phenotypic expression results in no change in the or- ganism’s adaptive value or fitness for present envi- ronmental conditions. 2. a mutation that has no measurable phenotypic effect as far as the study in question is concerned.

See silent mutation. neutral mutation-random drift theory of molecu- lar evolution a theory according to which the ma- jority of the nucleotide substitutions in the course of evolution are the result of the random fixation of neutral or nearly neutral mutations, rather than the result of positive Darwinian selection. Many protein polymorphisms are selectively neutral and are main- tained in a population by the balance between muta- tional input and random extinction. Neutral muta- tions are not functionless; they are simply equally effective to the ancestral alleles in promoting the survival and reproduction of the organisms that car- ry them. However, such neutral mutations can spread in a population purely by chance because only a rel- atively small number of gametes are “sampled” from the vast supply produced in each generation and therefore are represented in the individuals of the next generation.

See Appendix C, 1968, Kimura. neutron an elementary nuclear particle with a mass approximately the same as that of a hydrogen atom and electrically neutral; its mass is 1.0087 mass units. neutron contrast matching technique a tech- nique that involves determining the neutron-scatter- ing densities of particles irradiated in solutions con- taining various concentrations of light and heavy water. This technique was used on nucleosomes (q.v.), and it was found that under conditions where neutron scattering from DNA dominated the reac- tion, the radius of gyration was 50 A˚ngstroms. When scattering from the histone proteins was dominant, the radius was 30 A˚ngstroms. The larger radius for DNA proved that it was located on the surface of the nucleosome. See Appendix C, 1977, Pardon et al. N-formylmethionine a modified methionine mol- ecule that has a formyl group attached to its termi- nal amino group. Such an amino acid is “blocked” in the sense that the absence of a free amino group prevents the amino acid from being inserted into a growing polypeptide chain. N-formylmethionine is the starting amino acid in the synthesis of all bacte- rial polypeptides. See Appendix C, 1966, Adams and Cappecchi; initiator tRNA, start codon.

niacin an early name for nicotinic acid (q.v.). niche from the standpoint of a species, its behav- ioral, morphological, and physiological adaptations to its habitat. From the standpoint of the environ- ment, the ecological conditions under which the species survives and multiplies. See ecological niche, extremophiles. niche preclusion See first-arriver principle.

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