| Laboratory of Neurogenetics |
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| Glossary |
| Allele - a form of a gene. There may be multiple alleles of a given gene in the population. For example, at the ABO blood group locus, there are three alleles: A, B, and O. Different alleles do no imply pathogenic mutations per se (multiple alleles can lead to variability in certain traits, which all may be normal). Since each individual has two of each chromosome, they also have two alleles at a given gene locus. |
| Anticipation - when expansion of a triplet repeat mutation occurs progressively as it is passed from parent to child, causing the child to have a more severe phenotype or earlier age of onset than the affected parent. This phenomenon is sometimes more severe in paternal inheritance for unknown reasons. This phenomenon exists, for example, in Huntington's disease. |
| Association - in human genetic linkage studies, association studies frequently involve the comparison of allele frequencies for a marker locus between a disease population and in a control population. When statistically significant differences In the frequency of a n allele is found between a disease and control population, the disease and allele are said to be in association. |
| Associative Mating - where individuals seek out others with a similar phenotype as partners. |
| Autosome - a chromosome which does not determine sex of the individual. The normal human has 44 autosomes and 2 sex chromosomes. |
| Blepharospasm - cranial and focal dystonia affecting the eyelids. |
| Botulinum Toxin - toxin produced by bacterium Clostridium botulinum used to treat dystonia by intramuscular injection. |
| cDNA - a DNA copy of mRNA (messenger RNA) which is engineered using the enzyme reverse transcriptase. |
| CentiMorgan - a measure of genetic distance equivalent to 1/100 of a Morgan. A centiMorgan covers roughly 1 million base pairs (BP) of DNA and is about equivalent to 1% recombination. |
| Cervical Dystonia - also spasmodic torticollis, focal dystonia in which neck muscles cause abnormal postures and movements of the head/neck. |
| Chaperone Proteins - responsible for helping proteins fold and assume their three dimensional structure. |
| Chromosome - linear structure in the nucleus of the cell on which genes are located. These consist of DNA and proteins. Genes are organized on the strands of DNA. The normal human complement of chromosomes is 46 per somatic cell. |
| Cloning - this term has multiple meanings depending on usage. In molecular genetics, generally refers to the process in which a fragment of DNA or a copy of RNA is isolated in order for further study of the genes encoded therein. |
| Codon - three DNA bases, which encode a single amino acid. |
| Cosmid - vector which incorporates large quantities of foreign DNA. Useful for cloning purposes. |
| Crossover - the physical process that results in the exchange of genetic material between the two paired chromosomes during a recombination event. |
| Dinucleotide Repeat - a region of DNA in which there are multiple repeats of two nucleotide in succession. |
| Dopamine Agonist - drug that acts like dopamine, combines with dopamine receptors to mimic dopamine actions to create dopamine like effects. |
| dsDNA - double stranded DNA. |
| Exon - segment of a gene which contains information encoding a protein or portion of protein. |
| Expression - how a gene manifests itself. Expression is often "variable": one individual who carries the myotonic dystrophy gene may have only cataracts, while another may have myotonia. |
| Expressivity - degree to which a genetic trait is physically manifest, particularly in reference to that trait in an individual carrying a mutant gene. |
| Genetic Heterogeneity - The term which describes the situation in which several different mutations result in the same or similar phenotype. |
| Genotype - the observed alleles at a genetic locus for an individual. For autosomal loci, a genotype is composed of two alleles, one of which is paternally transmitted ant the other of which is maternally transmitted. |
| Haplotype - the linear, ordered arrangement of alleles on a chromosome. The haplotype is defined by the sequence of markers which are present along the chromosome in that section. |
| Heterogeneity - different causes for the same disease phenotype. |
| Heterozygous - having two different alleles at a given gene locus. |
| Homozygous - having the same allele at a given gene locus. |
| Hybridization - union of two nucleic acid strands (ssDNA) which share the same sequence to form a double helix (dsDNA). |
| Identity by Descent - two alleles are identical by descent (IBD) when it can be determined with certainty that they have been inherited from a common ancestor. |
| Infarction - tissue death. |
| Imprinting - different expression (phenotype) of a given gene depending on whether it is inherited from the mother or the father. For instance, when a certain part of chromosome 15 is missing, the child has Prader-Willi syndrome when inherited form the father, and Angelman syndrome when inherited from the mother. |
| In Situ Hybridization - a technique which allows hybridization of radio-labeled DNA to DNA in chromosomes which are fixed to a microscope slide. It is used to specifically stain DNA in chromosomes or for gene mapping. |
| Informant - a member of a family who is the source of information about the family relationships and affectation status; often, an unofficial member of the research team. |
| Intron - segment of a gene which contains information which is transcribed but then is spliced out of the transcript before the mature RNA is made. Thus, it does not code for a protein or part of a protein. |
| Linkage - presence of two genes very close together on a given chromosome. The closer they are, the more tightly they are linked, and the more likely they are to segregate together during meiosis and recombination. Thus, the more closely liked two loci are to one another, the greater the chance that both loci will be transmitted to offspring together. |
| Linkage Analysis - a laboratory technique in which an individual family is studied, and the likelihood of a given gene locus being responsible for a given trait is calculated statistically based on the sharing of chromosomal regions (haplotypes) among affected individuals in that family. |
| Locus - the place on a chromosome at which a given gene resides. |
| LOD (log of odds) Score - a base 10 logarithm of the likelihood of the odds ratio for linkage. This is a statistical means of assessing the likelihood of linkage between any two genetic markers. Typically, a LOD score of 3.0 (representing a 1:1000 chance that your statement that two regions are linked is wrong) is taken to be significant. A LOD score of -2.0 or less provides evidence against linkage. LOD scores are reported in association with a value of the recombination fraction (theta). |
| Marker Gene - a genetic locus used to follow the transmission of a gene responsible for disease in a given family. Marker genes have a known location, but often, their function is not known. They are useful only in yielding information regarding the location of a gene. |
| Markers - regions of DNA of known sequence and location on chromosomes which have known or unknown function. Markers can be used to isolate sections of chromosomes of interest (ie, haplotypes). |
| Mendelian - a term used to describe the inheritance of diseases which follow the classic patterns as originally described by the monk Gregor Mendel. Mendel described the inheritance of traits as autosomal dominant, autosomal recessive, X-linked recessive, X-linked dominant. |
| Microtubules - filaments within neurons, giving cells their characteristic shape and are involved in transport of cellular chemicals. |
| Missense Mutation - a type of point mutation that converts one codon (three letter code of A, G, C or T) to another specifying a different amino acid. Thus the wrong amino acid is synthesized in translation and thus a potentially faulty protein. |
| mRNA - messenger RNA. The final copy of a transcript of a gene which will be translated into a protein. |
| Multifactoral - a trait which has two or more genes interacting, along with the environment, to produce a phenotype. |
| Muscular Dystrophy - condition affecting the muscles and nerves causing weakness and movement difficulty. |
| Mutation - a change in a gene sequence which results in a difference in gene expression and a subsequent pathogenic phenotype. Sometimes referred to as a variant. |
| Neoplasm - new or abnormal growth of tissue. |
| Noninformative - an individual in a family studied for genetic linkage, who in not heterozygous at a marker locus, and therefore, for that individual, the coupling phase of the marker with a disease gene cannot be determined. |
| Nonsense Mutation - a mutation which converts a codon which further encodes an amino acid into a signal which lead to termination of translation. |
| Noradrenergic System - chemical signaling system between nerve cells that uses the neurotransmitter noradrenalin (norepinephrine). |
| Northern Blot - method of analysis of RNA. RNA is blotted onto a membrane and then hybridized with a labeled nucleic acid probe. |
| Oligonucleotide - segment of DNA which contains several nucleotides (usually about 15-30). |
| Oromandibular Dystonia - form of focal dystonia affecting varying areas of the head and neck, including jaw, tongue, larynx and lower face. |
| PCR - polymerase chain reaction. Method in which specific segment (oligonucleotide) of DNA is amplified using a set of oligonucleotide primers which flank the segment. The amplified DNA is used subsequently as the starting point for multiple rounds of DNA synthesis. |
| Penetrance - the probability that there will be a phenotypic manifestation of a genetic trait. In other words, the extent to which a given genotype results in the severity of an associated phenotype. When the genotype-phenotype association results in a variable degree of disease in indivduals, this is referred to as "reduced penetrance". |
| Phage - bacterial virus used as a vector for introducing DNA into bacteria, for cloning purposes. |
| Phenocopy - a trait which appears phenotypically to be identical to a given genetic trait, but which is caused by non-genetic factors. |
| Phenotype - the outward appearance of an individual with a disorder (ie, the clinical expression of the disorder). The phenotype may be expressed physically, biochemically, or physiologically, for example. |
| Plasmid - circular DNA molecule capable of replication in bacteria. A useful vector for gene cloning. |
| Pleiotropy - occurrence of a variety of seemingly unrelated manifestations, within a given affected individual, as a result of a single gene mutation. |
| Point Mutation - a change in one base pair of DNA. |
| Polygenic - a trait which is caused by the combined effects of two or more loci. |
| Polymorphism - existence of more than one allele for a gene. This also can be used to indicate that a change in a gene sequence which is of no apparent consequence or results in a phenotype which is not pathogenic. |
| Positional Cloning - cloning of a gene of unknown structure, and possibly function, using the information know about its location. |
| Proband - the individual in a pedigree who causes the pedigree to come to the attention of medical personnel; the index case identified in a family. |
| Promoter - region at the 5' end of a gene which serves as a starting point and control element for transcription. This region is very important in regulating gene expression. |
| Recombination - process during meiosis in which homologous chromosomes exchange segments. |
| Recombination Fraction (theta) - the frequency of crossing over between two loci. Estimates of the recombination fraction which are equal to 0.50 are consistent with the loci being unlinked to one anther. When theta = 0, the marker and disease gene are at the same locus. |
| Restriction Enzyme - enzyme which cuts DNA at a specific base sequence. |
| Reverse Transcriptase - enzyme which creates a DNA copy of an RNA molecule (this is backwards from the way it is usually done in the cell, in which RNA is made from DNA, hence the name). |
| RFLP - restriction fragment length polymorphism. |
| Somatic Cell Hybridization - process of gene mapping in which cells from two species are fused together, and the segregation of genetic trait is correlated with the retention of a particular chromosome in the hybrid cell. |
| Southern Blot - process of analysis of DNA blotted onto a membrane and hybridized with a labeled nucleic acid probe. |
| Spasmodic Torticollis - see cervical dystonia, the term is used to describe neck dystonias but more accurately describes sideway twisting of the neck, anterocollis and retrocollis mean forwards and backwards twisting of the neck. |
| Splicing - removal of introns from a transcript, leading to the continuous juxtaposition of exons in mRNA. |
| Tardive Dystonia - drug induced dystonia. |
| Tauopathies - group of diseases in which the tau protein in involved, includes diseases such as Pick's disease, progressive supranuclear palsy, frontotemporal dementia and parkinsonism, and corticobasal degeneration. |
| Tau Protein - a microtubule binding protein. |
| Trinucleotide Repeat - a sequence of DNA in which three nucleotides which recur multiple times. Trinucleotide repeats are seen in normal genes, but, very long trinucleotide repeats have been identified in some genetic diseases. One of the best known examples of trinucleotide repeat disease is Huntington's disease. |
| Vector - molecule capable of incorporating foreign DNA and then independently replication in a host cell. Used in gene cloning. |
| XDP - X-linked dystonia parkinsonism (Lubag). |
| X-linked Recessive - a gene on the X chromosome that has an effect only when there is no different gene present at the locus, since males only have on X chromosome, recessive traits are more common in males. |
| YAC - yeast artificial chromosome. Useful for cloning very large segments of DNA. |
| Author: Katrina Gwinn-Hardy, M,D. |
