The majority of this document was taken from: Primer on Molecular Genetics, DOE Human Genome Program, U.S. Department of Eneregy, Office of Energy Research, June, 1992

Adenine (A): A nitrogenous base, one member of the base pair A-T (adenine-thymine).

Alleles: Alternative forms of a genetic locus; a single allele for each locus is inherited separately from each parent (e.g., at a locus for eye color the allele might result in blue or brown eyes).

Amino acid: Any of a class of 20 molecules that are combined to form proteins in living things. The sequence of amino acids in a protein and hence protein function are determined by the genetic code.

Amplification: An increase in the number of copies of a specific DNA fragment; can be in vivo or in vitro. See cloning, polymerase chain reaction.

Arrayed library: Individual primary recombinant clones (hosted in phage, cosmid, YAC, or other vector) that are placed in two-dimensional arrays in microtiter dishes. Each primary clone can be identified by the identity of the plate and the clone location (row and column) on that plate. Arrayed libraries of clones can be used for many applications, including screening for a specific gene or genomic region of interest as well as for physical mapping. Information gathered on individual clones from various genetic linkage and physical map analyses is entered into a relational database and used to construct physical and genetic linkage maps simultaneously; clone identifiers serve to interrelate the multilevel maps. Compare library, genomic library.

Autoradiography: A technique that uses X-ray film to visualize radioactively labeled molecules or fragments of molecules; used in analyzing length and number of DNA fragments after they are separated by gel electrophoresis.

Autosome: A chromosome not involved in sex determination. The diploid human genome consists of 46 chromosomes, 22 pairs of autosomes, and 1 pair of sex chromosomes (the X and Y chromosomes).

Bacteriophage: See phage.

Base pair (bp): Two nitrogenous bases (adenine and thymine or guanine and cytosine) held together by weak bonds. Two strands of DNA are held together in the shape of a double helix by the bonds between base pairs.

Base sequence: The order of nucleotide bases in a DNA molecule.

Base sequence analysis: A method, sometimes automated, for determining the base sequence.

Biotechnology: A set of biological techniques developed through basic research and now applied to research and product development. In particular, the use by industry of recombinant DNA, cell fusion, and new bioprocessing techniques.

BLOSUM: Blocks Substitution Matrices for Protein Sequence Comparisons. A group of weighted scoring matricies for alignment of nucleotied or DNA sequences.

bp or bps: See base pair.

cDNA: See complementary DNA.

Centimorgan (cM): A unit of measure of recombination frequency. One centimorgan is equal to a 1% chance that a marker at one genetic locus will be separated from a marker at a second locus due to crossing over in a single generation. In human beings, 1 centimorgan is equivalent, on average, to 1 million base pairs.

Centromere: A specialized chromosome region to which spindle fibers attach during cell division.

Chromosomes: The self- replicating genetic structures of cells containing the cellular DNA that bears in its nucleotide sequence the linear array of genes. In prokaryotes, chromosomal DNA is circular, and the entire genome is carried on one chromosome. Eukaryotic genomes consist of a number of chromosomes whose DNA is associated with different kinds of proteins.

Clone bank: See genomic library.

Clones: A group of cells derived from a single ancestor.

Cloning: The process of asexually producing a group of cells (clones), all genetically identical, from a single ancestor. In recombinant DNA technology, the use of DNA manipulation procedures to produce multiple copies of a single gene or segment of DNA is referred to as cloning DNA.

Cloning vector: DNA molecule originating from a virus, a plasmid, or the cell of a higher organism into which another DNA fragment of appropriate size can be integrated without loss of the vectors capacity for self-replication; vectors introduce foreign DNA into host cells, where it can be reproduced in large quantities. Examples are plasmids, cosmids, and yeast artificial chromosomes; vectors are often recombinant molecules containing DNA sequences from several sources.

cM: See centimorgan.

Code: See genetic code.

Codon: See genetic code.

Complementary DNA (cDNA): DNA that is synthesized from a messenger RNA template; the single-stranded form is often used as a probe in physical mapping.

Complementary sequences: Nucleic acid base sequences that can form a double-stranded structure by matching base pairs; the complementary sequence to G-T-A-C is C-A-T-G.

Conserved sequence: A base sequence in a DNA molecule (or an amino acid sequence in a protein) that has remained essentially unchanged throughout evolution.

Contig map: A map depicting the relative order of a linked library of small overlapping clones representing a complete chromosomal segment.

Contigs: Groups of clones representing overlapping regions of a genome.

Cosmid: Artificially constructed cloning vector containing the cos gene of phage lambda. Cosmids can be packaged in lambda phage particles for infection into E. coli; this permits cloning of larger DNA fragments (up to 45 kb) than can be introduced into bacterial hosts in plasmid vectors.

Crossing over: The breaking during meiosis of one maternal and one paternal chromosome, the exchange of corresponding sections of DNA, and the rejoining of the chromosomes. This process can result in an exchange of alleles between chromosomes. Compare recombination.

Cytosine (C): A nitrogenous base, one member of the base pair G-C (guanine and cytosine).

Deoxyribonucleotide: See nucleotide.

Diploid: A full set of genetic material, consisting of paired chromosomes one chromosome from each parental set. Most animal cells except the gametes have a diploid set of chromosomes. The diploid human genome has 46 chromosomes. Compare haploid.

DNA (deoxyribonucleic acid): The molecule that encodes genetic information. DNA is a double-stranded molecule held together by weak bonds between base pairs of nucleotides. The four nucleotides in DNA contain the bases: adenine (A), guanine (G), cytosine (C), and thymine (T). In nature, base pairs form only between A and T and between G and C; thus the base sequence of each single strand can be deduced from that of its partner.

DNA probes: See probe.

DNA replication: The use of existing DNA as a template for the synthesis of new DNA strands. In humans and other eukaryotes, replication occurs in the cell nucleus.

DNA sequence: The relative order of base pairs, whether in a fragment of DNA, a gene, a chromosome, or an entire genome. See base sequence analysis.

Domain: A discrete portion of a protein with its own function. The combination of domains in a single protein determines its overall function.

Double helix: The shape that two linear strands of DNA assume when bonded together.

E. coli: Common bacterium that has been studied intensively by geneticists because of its small genome size, normal lack of pathogenicity, and ease of growth in the laboratory.

Electrophoresis: A method of separating large molecules (such as DNA fragments or proteins) from a mixture of similar molecules. An electric current is passed through a medium containing the mixture, and each kind of molecule travels through the medium at a different rate, depending on its electrical charge and size. Separation is based on these differences. Agarose and acrylamide gels are the media commonly used for electrophoresis of proteins and nucleic acids.

Endonuclease: An enzyme that cleaves its nucleic acid substrate at internal sites in the nucleotide sequence.

Enzyme: A protein that acts as a catalyst, speeding the rate at which a biochemical reaction proceeds but not altering the direction or nature of the reaction.

EST: Expressed sequence tag. See sequence tagged site.

Eukaryote: Cell or organism with membrane-bound, structurally discrete nucleus and other well-developed subcellular compartments. Eukaryotes include all organisms except viruses, bacteria, and blue-green algae. Compare prokaryote. See chromosomes.

Evolutionarily conserved: See conserved sequence.

Exogenous DNA: DNA originating outside an organism.

Exons: The protein-coding DNA sequences of a gene. Compare introns.

Exonuclease: An enzyme that cleaves nucleotides sequentially from free ends of a linear nucleic acid substrate.

Expressed gene: See gene expression.

FISH (fluorescence in situ hybridization): A physical mapping approach that uses fluorescein tags to detect hybridization of probes with metaphase chromosomes and with the less-condensed somatic interphase chromatin.

Flow cytometry: Analysis of biological material by detection of the light- absorbing or fluorescing properties of cells or subcellular fractions (i.e., chromosomes) passing in a narrow stream through a laser beam. An absorbance or fluorescence profile of the sample is produced. Automated sorting devices, used to fractionate samples, sort successive droplets of the analyzed stream into different fractions depending on the fluorescence emitted by each droplet.

Flow karyotyping: Use of flow cytometry to analyze and/or separate chromosomes on the basis of their DNA content.

Gamete: Mature male or female reproductive cell (sperm or ovum) with a haploid set of chromosomes (23 for humans).

Gene: The fundamental physical and functional unit of heredity. A gene is an ordered sequence of nucleotides located in a particular position on a particular chromosome that encodes a specific functional product (i.e., a protein or RNA molecule). See gene expression.

Gene expression: The process by which a genes coded information is converted into the structures present and operating in the cell. Expressed genes include those that are transcribed into mRNA and then translated into protein and those that are transcribed into RNA but not translated into protein (e.g., transfer and ribosomal RNAs).

Gene families: Groups of closely related genes that make similar products.

Gene library: See genomic library.

Gene mapping: Determination of the relative positions of genes on a DNA molecule (chromosome or plasmid) and of the distance, in linkage units or physical units, between them.

Gene product: The biochemical material, either RNA or protein, resulting from expression of a gene. The amount of gene product is used to measure how active a gene is; abnormal amounts can be correlated with disease-causing alleles.

Genetic code: The sequence of nucleotides, coded in triplets (codons) along the mRNA, that determines the sequence of amino acids in protein synthesis. The DNA sequence of a gene can be used to predict the mRNA sequence, and the genetic code can in turn be used to predict the amino acid sequence.

Genetic engineering technologies: See recombinant DNA technologies.

Genetic map: See linkage map.

Genetic material: See genome.

Genetics: The study of the patterns of inheritance of specific traits.

Genome: All the genetic material in the chromosomes of a particular organism; its size is generally given as its total number of base pairs.

Genome projects: Research and technology development efforts aimed at mapping and sequencing some or all of the genome of human beings and other organisms.

Genomic library: A collection of clones made from a set of randomly generated overlapping DNA fragments representing the entire genome of an organism. Compare library, arrayed library.

Global Alignment:Alignment of A within B (like agrep) Allows for gaps.

Guanine (G): A nitrogenous base, one member of the base pair G-C (guanine and cytosine).

Haploid: A single set of chromosomes (half the full set of genetic material), present in the egg and sperm cells of animals and in the egg and pollen cells of plants. Human beings have 23 chromosomes in their reproductive cells. Compare diploid.

Heterozygosity: The presence of different alleles at one or more loci on homologous chromosomes.

Homeobox: A short stretch of nucleotides whose base sequence is virtually identical in all the genes that contain it. It has been found in many organisms from fruit flies to human beings. In the fruit fly, a homeobox appears to determine when particular groups of genes are expressed during development.

Homologies: Similarities in DNA or protein sequences between individuals of the same species or among different species.

Homologous chromosomes: A pair of chromosomes containing the same linear gene sequences, each derived from one parent.

Highest Scoring Pairs(hsp): The the highest scoring pair of alignments between two nucleotides or amino acids sequences.

Human gene therapy: Insertion of normal DNA directly into cells to correct a genetic defect.

Human Genome Initiative: Collective name for several projects begun in 1986 by DOE to (1) create an ordered set of DNA segments from known chromosomal locations, (2) develop new computational methods for analyzing genetic map and DNA sequence data, and (3) develop new techniques and instruments for detecting and analyzing DNA. This DOE initiative is now known as the Human Genome Program. The national effort, led by DOE and NIH, is known as the Human Genome Project.

Hybridization: The process of joining two complementary strands of DNA or one each of DNA and RNA to form a double-stranded molecule.

InDels: Insertion or Deletion. The insertion or deletion of an amino acid or nucleotide from a protine or DNA sequence.

Informatics: The study of the application of computer and statistical techniques to the management of information. In genome projects, informatics includes the development of methods to search databases quickly, to analyze DNA sequence information, and to predict protein sequence and structure from DNA sequence data.

In situ hybridization: Use of a DNA or RNA probe to detect the presence of the complementary DNA sequence in cloned bacterial or cultured eukaryotic cells.

Interphase: The period in the cell cycle when DNA is replicated in the nucleus; followed by mitosis.

Introns: The DNA base sequences interrupting the protein- coding sequences of a gene; these sequences are transcribed into RNA but are cut out of the message before it is translated into protein. Compare exons.

In vitro: Outside a living organism.

Karyotype: A photomicrograph of an individuals chromosomes arranged in a standard format showing the number, size, and shape of each chromosome type; used in low-resolution physical mapping to correlate gross chromosomal abnormalities with the characteristics of specific diseases.

kb: See kilobase.

Kilobase (kb): Unit of length for DNA fragments equal to 1000 nucleotides.

k-tuple (k-tup): a size "k" tuple of nucleotides or amino acids.

Library: An unordered collection of clones (i.e., cloned DNA from a particular organism), whose relationship to each other can be established by physical mapping. Compare genomic library, arrayed library.

Linkage: The proximity of two or more markers (e.g., genes, RFLP markers) on a chromosome; the closer together the markers are, the lower the probability that they will be separated during DNA repair or replication processes (binary fission in prokaryotes, mitosis or meiosis in eukaryotes), and hence the greater the probability that they will be inherited together.

Linkage map: A map of the relative positions of genetic loci on a chromosome, determined on the basis of how often the loci are inherited together. Distance is measured in centimorgans (cM).

Global Alignment:Alignment of A to B like (diff) Looks for Longest Common Subsequence (LCS).

Localize: Determination of the original position (locus) of a gene or other marker on a chromosome.

Locus (pl. loci): The position on a chromosome of a gene or other chromosome marker; also, the DNA at that position. The use of locus is sometimes restricted to mean regions of DNA that are expressed. See gene expression.

Longest Commmon Subequence (lcs): The longest sequence of nucleotides or amino acids common to two sequences.

Macrorestriction map: Map depicting the order of and distance between sites at which restriction enzymes cleave chromosomes.

Mapping: See gene mapping, linkage map, physical map.

Marker: An identifiable physical location on a chromosome (e.g., restriction enzyme cutting site, gene) whose inheritance can be monitored. Markers can be expressed regions of DNA (genes) or some segment of DNA with no known coding function but whose pattern of inheritance can be determined. See RFLP, restriction fragment length polymorphism.

Mb: See megabase.

Megabase (Mb): Unit of length for DNA fragments equal to 1 million nucleotides and roughly equal to 1 cM.

Meiosis: The process of two consecutive cell divisions in the diploid progenitors of sex cells. Meiosis results in four rather than two daughter cells, each with a haploid set of chromosomes.

Messenger RNA (mRNA): RNA that serves as a template for protein synthesis. See genetic code.

Metaphase: A stage in mitosis or meiosis during which the chromosomes are aligned along the equatorial plane of the cell.

Mitosis: The process of nuclear division in cells that produces daughter cells that are genetically identical to each other and to the parent cell.

mRNA: See messenger RNA.

Multifactorial or multigenic disorders: See polygenic disorders.

Multiple Alignment: A sequencing approach that simultaneously aligns n sequences.

Multiplexing: A sequencing approach that uses several pooled samples simultaneously, greatly increasing sequencing speed.

Mutation: Any heritable change in DNA sequence. Compare polymorphism.

Nitrogenous base: A nitrogen-containing molecule having the chemical properties of a base.

Nucleic acid: A large molecule composed of nucleotide subunits.

Nucleotide: A subunit of DNA or RNA consisting of a nitrogenous base (adenine, guanine, thymine, or cytosine in DNA; adenine, guanine, uracil, or cytosine in RNA), a phosphate molecule, and a sugar molecule (deoxyribose in DNA and ribose in RNA). Thousands of nucleotides are linked to form a DNA or RNA molecule. See DNA, base pair, RNA.

Nucleus: The cellular organelle in eukaryotes that contains the genetic material.

Oncogene: A gene, one or more forms of which is associated with cancer. Many oncogenes are involved, directly or indirectly, in controlling the rate of cell growth.

Overlapping clones: See genomic library.

PAM: Percent Accepted Mutation. A group of weighted scoring matricies for alignment of nucleotied or DNA sequences.

PCR: See polymerase chain reaction.

Phage: A virus for which the natural host is a bacterial cell.

Physical map: A map of the locations of identifiable landmarks on DNA (e.g., restriction enzyme cutting sites, genes), regardless of inheritance. Distance is measured in base pairs. For the human genome, the lowest-resolution physical map is the banding patterns on the 24 different chromosomes; the highest-resolution map would be the complete nucleotide sequence of the chromosomes.

Plasmid: Autonomously replicating, extrachromosomal circular DNA molecules, distinct from the normal bacterial genome and nonessential for cell survival under nonselective conditions. Some plasmids are capable of integrating into the host genome. A number of artificially constructed plasmids are used as cloning vectors.

Polygenic disorders: Genetic disorders resulting from the combined action of alleles of more than one gene (e.g., heart disease, diabetes, and some cancers). Although such disorders are inherited, they depend on the simultaneous presence of several alleles; thus the hereditary patterns are usually more complex than those of single-gene disorders. Compare single-gene disorders.

Polymerase chain reaction (PCR): A method for amplifying a DNA base sequence using a heat-stable polymerase and two 20-base primers, one complementary to the (+)-strand at one end of the sequence to be amplified and the other complementary to the (-)-strand at the other end. Because the newly synthesized DNA strands can subsequently serve as additional templates for the same primer sequences, successive rounds of primer annealing, strand elongation, and dissociation produce rapid and highly specific amplification of the desired sequence. PCR also can be used to detect the existence of the defined sequence in a DNA sample.

Polymerase, DNA or RNA: Enzymes that catalyze the synthesis of nucleic acids on preexisting nucleic acid templates, assembling RNA from ribonucleotides or DNA from deoxyribonucleotides.

Polymorphism: Difference in DNA sequence among individuals. Genetic variations occurring in more than 1% of a population would be considered useful polymorphisms for genetic linkage analysis. Compare mutation.

Primer: Short preexisting polynucleotide chain to which new deoxyribonucleotides can be added by DNA polymerase.

Probe: Single-stranded DNA or RNA molecules of specific base sequence, labeled either radioactively or immunologically, that are used to detect the complementary base sequence by hybridization.

Prokaryote: Cell or organism lacking a membrane-bound, structurally discrete nucleus and other subcellular compartments. Bacteria are prokaryotes. Compare eukaryote. See chromosomes.

Promoter: A site on DNA to which RNA polymerase will bind and initiate transcription.

Protein: A large molecule composed of one or more chains of amino acids in a specific order; the order is determined by the base sequence of nucleotides in the gene coding for the protein. Proteins are required for the structure, function, and regulation of the bodys cells, tissues, and organs, and each protein has unique functions. Examples are hormones, enzymes, and antibodies.

Purine: A nitrogen-containing, single-ring, basic compound that occurs in nucleic acids. The purines in DNA and RNA are adenine and guanine.

Pyrimidine: A nitrogen-containing, double-ring, basic compound that occurs in nucleic acids. The pyrimidines in DNA are cytosine and thymine; in RNA, cytosine and uracil.

Rare-cutter enzyme: See restriction enzyme cutting site.

Recombinant clones: Clones containing recombinant DNA molecules. See recombinant DNA technologies.

Recombinant DNA molecules: A combination of DNA molecules of different origin that are joined using recombinant DNA technologies.

Recombinant DNA technologies: Procedures used to join together DNA segments in a cell-free system (an environment outside a cell or organism). Under appropriate conditions, a recombinant DNA molecule can enter a cell and replicate there, either autonomously or after it has become integrated into a cellular chromosome.

Recombination: The process by which progeny derive a combination of genes different from that of either parent. In higher organisms, this can occur by crossing over.

Regulatory regions or sequences: A DNA base sequence that controls gene expression.

Resolution: Degree of molecular detail on a physical map of DNA, ranging from low to high.

Restriction enzyme, endonuclease: A protein that recognizes specific, short nucleotide sequences and cuts DNA at those sites. Bacteria contain over 400 such enzymes that recognize and cut over 100 different DNA sequences. See restriction enzyme cutting site.

Restriction enzyme cutting site: A specific nucleotide sequence of DNA at which a particular restriction enzyme cuts the DNA. Some sitesoccur frequently in DNA (e.g., every several hundred base pairs), others much less frequently (rare-cutter; e.g., every 10,000 base pairs).

Restriction fragment length polymorphism (RFLP): Variation between individuals in DNA fragment sizes cut by specific restriction enzymes; polymorphic sequences that result in RFLPs are used as markers on both physical maps and genetic linkage maps. RFLPs are usually caused by mutation at a cutting site. See marker.

RFLP: See restriction fragment length polymorphism.

Ribonucleic acid (RNA): A chemical found in the nucleus and cytoplasm of cells; it plays an important role in protein synthesis and other chemical activities of the cell. The structure of RNA is similar to that of DNA. There are several classes of RNA molecules, including messenger RNA, transfer RNA, ribosomal RNA, and other small RNAs, each serving a different purpose.

Ribonucleotides: See nucleotide.

Ribosomal RNA (rRNA): A class of RNA found in the ribosomes of cells.

Ribosomes: Small cellular components composed of specialized ribosomal RNA and protein; site of protein synthesis. See ribonucleic acid (RNA).

RNA: See ribonucleic acid.

Sequence: See base sequence.

Sequence tagged site (STS): Short (200 to 500 base pairs) DNA sequence that has a single occurrence in the human genome and whose location and base sequence are known. Detectable by polymerase chain reaction, STSs are useful for localizing and orienting the mapping and sequence data reported from many different laboratories and serve as landmarks on the developing physical map of the human genome. Expressed sequence tags (ESTs) are STSs derived from cDNAs.

Sequencing: Determination of the order of nucleotides (base sequences) in a DNA or RNA molecule or the order of amino acids in a protein.

Sex chromosomes: The X and Y chromosomes in human beings that determine the sex of an individual. Females have two X chromosomes in diploid cells; males have an X and a Y chromosome. The sex chromosomes comprise the 23rd chromosome pair in a karyotype. Compare autosome.

Shotgun method: Cloning of DNA fragments randomly generated from a genome. See library, genomic library.

Single-gene disorder: Hereditary disorder caused by a mutant allele of a single gene (e.g., Duchenne muscular dystrophy, retinoblastoma, sickle cell disease). Compare polygenic disorders.

Somatic cells: Any cell in the body except gametes and their precursors.

Southern blotting: Transfer by absorption of DNA fragments separated in electrophoretic gels to membrane filters for detection of specific base sequences by radiolabeled complementary probes.

STS: See sequence tagged site.

Tandem repeat sequences: Multiple copies of the same base sequence on a chromosome; used as a marker in physical mapping.

Technology transfer: The process of converting scientific findings from research laboratories into useful products by the commercial sector.

Telomere: The ends of chromosomes. These specialized structures are involved in the replication and stability of linear DNA molecules. See DNA replication.

Thymine (T): A nitrogenous base, one member of the base pair A-T (adenine-thymine).

Transcription: The synthesis of an RNA copy from a sequence of DNA (a gene); the first step in gene expression. Compare translation.

Transfer RNA (tRNA): A class of RNA having structures with triplet nucleotide sequences that are complementary to the triplet nucleotide coding sequences of mRNA. The role of tRNAs in protein synthesis is to bond with amino acids and transfer them to the ribosomes, where proteins are assembled according to the genetic code carried by mRNA.

Transformation: A process by which the genetic material carried by an individual cell is altered by incorporation of exogenous DNA into its genome.

Transition: The term proposed by Freese (1959) for a mutation caused by the substitution in DNA or RNA of one purine by the other, and similarly with the pyrimidines. (see transversion)

Translation: The process in which the genetic code carried by mRNA directs the synthesis of proteins from amino acids. Compare transcription.

Transversion: The term proposed by Freese (1959) for a mutation caused by the substitution of a purine for a pyrimidine, and vice versa, in DNA or RNA. (see Transition).

tRNA: See transfer RNA.

Uracil: A nitrogenous base normally found in RNA but not DNA; uracil is capable of forming a base pair with adenine.

Vector: See cloning vector.

Virus: A noncellular biological entity that can reproduce only within a host cell. Viruses consist of nucleic acid covered by protein; some animal viruses are also surrounded by membrane. Inside the infected cell, the virus uses the synthetic capability of the host to produce progeny virus.

VLSI: Very large-scale integration allowing over 100,000 transistors on a chip.

YAC: See yeast artificial chromosome.

Yeast artificial chromosome (YAC): A vector used to clone DNA fragments (up to 400 kb); it is constructed from the telomeric, centromeric, and replication origin sequences needed for replication in yeast cells. Compare cloning vector, cosmid.