Gas-flow radiation counter
gas-flow radiation counter a counter in which an appropriate atmosphere is maintained in the sensi- tive volume by allowing a suitable gas to flow slowly through it. gastrin a hormone secreted by the stomach that causes secretion of digestive enzymes by other stom- ach cells. Gastropoda the class of molluscs containing the snails. See Appendix A. gastrula the stage of embryonic development when the gastrulation movements occur. gastrulation the complex cell movements that carry those cells whose descendants will form the fu- ture internal organs from their largely superficial position in the blastula to approximately their de- finitive positions inside the animal embryo. Prior to gastrulation, the amphibian embryo relies on RNA molecules pre-loaded into the ooplasm during oo- genesis.
During gastrulation, however, newly synthe- sized nuclear gene products are required. Gaucher disease the most common hereditary disorder of glycolipid metabolism, due to mutations in a gene on chromosome 1 at position q21. The gene contains 11 exons, that encode a 7,500 base pair transcript that specifies the enzyme glucocere- brosidase. This cleaves glucose from cerebrosides, and glucocerebrosides accumulate in lysosomes when the enzyme is defective. Although the enzyme defi- ciency exists in all the cells of persons with the dis- ease, the cell primarily responsible for the syndrome is the macrophage (q.v.).
Macrophages swollen by the accumulation of glucocerebrosides are called Gaucher cells. An effective treatment involves infusing the patient with a genetically engineered glucocerebrosi- dase, which is specifically targeted to Gaucher cells. Unfortunately, the treatment is tremendously ex- pensive, amounting to $200,000 per year or more. The most common mutations of the cerebrosidase gene are missense mutations, and the positions of the amino acid substitutions often determine whether the condition will be mild or severe. Five common mutations collectively account for over 95% of the cases of Gaucher disease in the Ashkenazi Jewish population.
These alleles occur in a frequency far higher than could be sustained by mutation. Hetero- zygotes can be identified because their peripheral leukocytes show lower enzyme levels. Homozygotes can be detected in utero by assays run on cells ob- tained by amniocentesis. Adjacent to the Gaucher disease gene is a pseudogene that also contains 11 exons. In the regions present in both sequences, 96% of the nucleotides are identical. The pseudogene is smaller because of large deletions in four of the in- trons and small deletions in two of the exons.
Some alleles responsible for Gaucher disease symptoms appear to have arisen by rearrangements between the structural gene and the pseudogene. The first de- scription of the disease was published in 1882 by Dr. Philippe Gaucher, hence the eponym. See Appendix C, 1989, Horowitz et al.; Ashkenazi, cerebrosidase, lysosomal storage diseases, Tay-Sachs disease. http:// www.gaucherdisease.org. Gaussian curve See normal distribution. G banding See chromosome banding techniques. gb, gbp See gigabase, gigabase pairs. GDB Genome Data Base (human) See Appendix E. Geiger-Mueller (G-M) counter a sensitive gas- filled radiation-measuring device.
gel diffusion technique See immunoelectrophore- sis, Ouchterlony technique, Oudin technique. gemma (plural, gemmae) a multicellular, asexual reproductive structure, such as a bud or a plant frag- ment. gemmules pangenes. See pangenesis. gene the definition of a gene changes as more of its properties are revealed. In the classical literature it is defined as a hereditary unit that occupies a spe-
Characteristics of Genes Responsible for Five Human Diseases
cific position (locus) within the genome or chromo- some; a unit that has one or more specific effects upon the phenotype of the organism; a unit that can mutate to various allelic forms; and a unit that recombines with other such units. Two classes are now recognized: (1) genes that are transcribed into mRNAs, which enter ribosomes and are translated into polypeptide chains, and (2) genes whose tran- scripts (tRNAs, rRNAs, snRNAs, etc.) are used di- rectly.
Class 1 genes are called structural genes or cis- trons in the earlier literature. As shown in the table on page 172, structural genes vary greatly in size. Some genes that are transcribed into mRNAs can undergo alternative splicing and generate a series of structurally related proteins. There are also shorter DNA segments that are not transcribed but serve as recognition sites for enzymes and other proteins that function during transcription or replication.
Some of these elements (i.e., operators) fulfill the classical definition of genes, but now they are generally called regulatory sequences. These should not be confused with regulatory genes, which encode (1) proteins that bind to regulatory sequences in other parts of the ge- nome or (2) RNAs that inactivate entire chromo- somes. The i gene of the lac operon is an example of a regulatory gene of the first type. The Xist gene is an example of the second type. It encodes an RNA that inactivates an entire X chromosome and is responsi- ble for dosage compensation in female mammals. See Appendix C, 1909, Johannsen; 1933, Morgan; 1955, Benzer; 1961, Jacob and Monod; 1975, King and Wilson; dosage compensation, isoform, lac operon, replicon, selector gene, transcription unit, Xist.
gene activation See genetic induction. genealogy a record of the descent of a family, group, or person from an ancestor or ancestors; lin- eage; pedigree. gene amplification any process by which specific DNA sequences are replicated to a disproportion- ately greater degree than their representation in the parent molecules. During development, some genes become amplified in specific tissues; e.g., rRNA genes amplify and become active during oogenesis, especially in some amphibian oocytes (see rDNA am- plification, Xenopus). Genes encoding Drosophila chorion proteins are also amplified in ovarian follicle cells. Gene amplification can be induced by treating cultured cells with drugs like methotrexate (q.v.). Gene amplification is a common and critically im- portant defect in cancer cells. For example, a specific set of autosomal genes is overexpressed in oral squa- mous cell carcinomas.
See Appendix C, 1968, Gall, Brown, and Dawid; 1978, Schimke et al.; 2002, Hu- ang et al.; amplicon, genomic equivalence, Podospora anserina, Rhynchosciara, TAOS 1. gene bank See genomic library. GeneCards a database of human genes, their prod- ucts, and their involvement in diseases assembled by M. Rebhan and three colleagues at the Weizmann Institute of Science, Rehovot, Israel. http://bioinfor- matics.weizmann.ac.il/cards. gene cloning creation of a line of genetically iden- tical organisms, containing recombinant DNA mole- cules, which can be propagated and grown in bulk, thus amplifying the recombinant molecules. gene cloning vehicle See lambda cloning vector, plasmid cloning vector. gene cluster See multigene family. gene conversion a situation in which the products of meiosis from an AA′ individual are 3A and 1A′ or 1A and 3A′, not 2A and 2A′ as is usually the case. Thus, one gets the impression that one A gene has been converted to an A′ gene (or vice versa). Gene conversion is thought to involve a rare error in DNA repair that occurs while recombination is going on during meiotic prophase.
A double-strand break in one bivalent is enlarged to eliminate one allele of the sister strand. When the gap is repaired, a non-sister strand carrying the alternate allele is used as a tem- plate, with the result that the tetrad comes to con- tain three copies of one allele and one of the other. Therefore gene conversion leads to the unequal re- covery of alleles from DNA molecules that each carry a pair of alleles, one normal and one defective. The human Y chromosome contains several palin- dromes (q.v.) in which are imbedded structural genes that function in spermatogenesis. Within each palindrome, multiple copies of structural genes function as templates for repair of mutated genes. In this way gene conversion prevents the Y from accu- mulating sterility mutations. See Appendix C, 1935, Lindgren; 2003, Skaletsky et al. gene dosage the number of times a given gene is present in the nucleus of a cell. gene duplication the production of a tandem re- peat of a DNA sequence by unequal crossing over (q.v.) or by an accident of replication. Duplicated genes created in these ways may subsequently evolve new functions. See hemoglobin genes, repeat-in- duced point mutation (RIP). gene expression the display of genetic activity by the synthesis of gene products that affect the pheno- type. Some genes are active throughout the life of