Glossary

Acquired Disease
A disease not present at birth, such as coronary heart disease, diabetes, or mental illness. See Congenital.

ADME (Absorption, Distribution, Metabolism, and Excretion)
To be an effective drug, a compound not only must be active against a target, but also possess the appropriate ADME (Absorption, Distribution, Metabolism, and Excretion) properties necessary to make it suitable for use as a drug.

Allele
One of alternative forms at a genetic locus on a single chromosome. For loci in most of the genome, a human has two chromosomes, which may carry the same or two different alleles.

Amino Acid
Any of the 20 subunits that are the basic building blocks of proteins.

Amplicon
The product of PCR or LCR; a piece of DNA that has been synthesized using amplification techniques.

Amplification Of DNA
The production of many DNA copies from one or a few copies.

Annealing
Spontaneous alignment of two complementary single polynucleotide (RNA, DNA, or RNA and DNA) strands to form a double helix.

Autosomal Dominant
A dominant allele whose gene is located on an autosome.

Autosomal Recessive
A recessive allele whose gene is located on an autosome.

Autosome
Any of the "numbered" chromosomes -- not the X, Y, or mitochondrial chromosomes. Each human has two copies of each; one inherited from the mother and one from the father. The X and Y chromosomes are different from the autosomes because men have one X and one Y chromosome, whereas women have two X chromosomes.

BAC (Bacterial Artificial Chromosome)
A vector used to clone DNA fragments of 100 to 300 kb insert size in Escherichia coli cells.

Bacteriophage
A virus that infects bacteria.

Biomarker
A molecular marker associated with a biological function.

Cell
The basic structural unit of most living things. Each cell is like a bag or a box with a surface that interacts with its environment and watery interior, where most chemical reactions take place. Gates and channels in the cell surface actively maintain the conditions inside a cell. Each cell typically contains an entire copy of the organism's genome. Cells also communicate with other cells. Cells in a complex organism, such as a human being, differentiate from one another over the course of development following conception. Different cell types emerge and take on dramatically different roles, such as communication, transportation, metabolism and defense.

Chromosome
The structures in which DNA, and hence genes, are housed. DNA does not float free in cells. It is gathered into bundles called chromosomes. Each chromosome is a single, very long strand of the DNA double helix, plus "packing material." Just before a cell divides, however, the chromosomes replicate their DNA. In this state, chromosomes look like the letter X.

Each chromosome has a few thousand genes on it. Human chromosomes are small -- a microscope is required to see them. Chromosomes are not visible under the microscope unless they are stained. The DNA in a chromosome is tightly packed and curled. Stretched out in a straight line, the DNA is about 10,000 times longer than the chromosome.

Cloning
(1) Using specialized DNA technology to produce multiple, exact copies of a single gene or other segment of DNA to obtain enough material for further study. The resulting cloned (copied) collections of DNA molecules are called clone libraries. (2) A second type of cloning exploits the natural process of cell division to make many copies of an entire cell. The genetic makeup of these cloned cells, called a cell line, is identical to the original cell. (3) A third type of cloning produces complete, genetically identical animals.

Codon
Triplets of nucleotides that lie along the messenger RNA (mRNA) molecule and encode the sequence of amino acids in a protein.

Congenital
Inborn. When a person is born with a condition, the condition is called congenital. See Acquired Disease.

Cosmid
A hybrid plasmid that contains cos sites at each end. Cos sites are recognized during head filling of lambda phages. Cosmids are useful for cloning large segments of foreign DNA (up to 50 kb).

DecoGen Informatics System
Cogenics’ proprietary informatics platform, named for its ability to decode genes. The system consists of proprietary databases of population information for our Index Repository and for our HAP™ Markers (HAP® Database), which includes HAP™ Marker sequence, frequency and distribution. The portal to the HAP® Database is a search engine, which is powered by a proprietary collection of algorithms and which has been designed with an intuitive, graphical user interface. The search engine can determine with statistical accuracy the correlation between a drug response and HAP™ Markers in a small population of the size commonly used in phase I or phase II of a clinical trial.

Denaturation
The separation of the two strands of a DNA double helix.

Directed Mutagenesis
Altering some specific part of a cloned gene and reintroducing the modified gene back into the organism.

DNA (Deoxyribonucleic Acid)
A double stranded molecule, organized as a double helix, which contains genetic information, primarily in the form of genes. The helix consists of a sugar-phosphate backbone with chemical bases that extend from the backbone. There are four different bases in DNA: adenine (A), thymine (T), guanine (G) and cytosine (C). The bases on one strand can only pair with a specific base on the other strand. A always pairs with T, and G always pairs with C. The order of these bases determines the function of the DNA.

DNA Sequencing
Procedures for determining the nucleotide sequence of a DNA fragment.

Dominant
The property of an allele whereby possessing either one or two copies of the allele results in the same phenotype. Contrast with recessive.

Environment
Factors outside the human body. To a geneticist, the environment is everything that is not genetic. Some aspects of the environment that influence health and disease include:

• Diet -- food, preservatives, coloring, method of preparation (smoked foods, for example), composition of diet (fats, carbohydrates, protein), and amount.
• Air -- clean air, smog, pollution, tobacco, workplace chemical fumes, dust (coal, cotton, etc.), humidity, temperature.
• Water -- everything we drink, cook, or bathe in. Also, fluoride, pesticides, minerals.
• Radiation -- sunlight, tanning lights, radiation (X rays, microwaves, radio waves).
• Infection -- bacteria, viruses, fungi, parasites. Also includes infection-related factors, such as sanitation and proximity to people, animals, or insects.

Enzyme
A specialized protein that acts as a catalyst, a protein that speeds up chemical reactions within a cell.

Exons
DNA segments of a gene that encode the amino acid sequence of a protein.

Gene
A piece of DNA that includes the code for a specific protein, as well as some of the code for when and where the protein is made. A gene occupies a specific place, or locus, on a chromosome.

Gene Expression
The process of producing a protein from its DNA- and mRNA-coding sequences.

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

Genetic Map
The relative position of genes contained in the DNA of a chromosome.

Genetic Marker
An allele or genotype, typically unrelated to the phenotype of interest, that is nonetheless useful for predicting the phenotype due to the marker's proximity to the locus that is functionally producing the phenotype.

Genome
The total genetic content of an organism, comprising genes and all other DNA sequences. Only about 4-5% of the human genome is estimated to constitute gene information. The function of the remaining DNA is unclear, but some is likely to have a role in maintaining stability of the genome.

Genotype
The specific genetic variants at one or more locus of an individual. Typically, the two chromosomal copies of a polymorphic site. For instance, A/A or A/G or G/G. Can also be used as a verb, meaning the determination of such genotype(s).

HAP® Database
The compilation of annotated data on the identity, frequency and distribution of SNPs, SNP alleles, and HAP™ Markers generated by examining genomic DNA from Cogenics’ Index Repository.

Haplotype
The alleles found on a single chromosome present at the known polymorphic sites in a gene or region of genomic DNA. The two haplotypes of a gene carried by an individual are that individual's alleles for the gene.

HAP™ Marker
A derivation of the technical term haplotype, which at the molecular level, is a combination of nucleotides that are present at each of the polymorphic sites on a chromosome in selected regions of a gene. These selected regions include the region immediately upstream of the first coding exon (the promoter); the protein coding regions (exons); the intron/exon boundaries; and the last exon through at least the termination codon. A HAP™ Marker is discovered by Cogenics electronically using proprietary algorithms based on well-established genetic principles.

HAP™ Typing
HAP™ Typing describes the process of determining which HAP™ Marker is present for each of the two versions of a gene in a patient's clinical sample.

Heterozygous
Having two different alleles for a particular polymorphism.

Homozygous
Having two copies of a single allele for a particular polymorphism. Recessive traits require homozygosity to be observed.

Hybridization
Coming together (annealling) of single-stranded nucleic acid sequences by hydrogen bonding of complementary bases to form double-stranded molecules; this process is the basis for molecular biological techniques in which a labeled probe sequence is used to detect another identical or similar sequence.

Index Repository
Cogenics’ collection of immortalized cell lines established from unrelated individuals and members of extended families. The individuals were chosen to represent a large proportion of human diversity, facilitate the quality control analysis of the polymorphic discovery process and enable the electronic discovery of Cogenics’ HAP™ Markers.

Informatics
Storing, manipulating, analyzing and visualizing information using computer systems.

Inheritance
The passing on of genetic material from parents to offspring.

Intron
The DNA base sequences interrupting the protein-coding sequences of a gene in genomic DNA; these sequences are transcribed into RNA but are cut out (spliced out) of the messenger RNA (mRNA) before it is translated into a protein molecule.

in vitro
In an experimental situation outside the organism. Biological or chemical work done in the test tube (in vitro is Latin for "in glass") rather than in living systems.

in vivo
In a living cell or organism.

Library
A collection of clones (usually kept in bacteria or yeast), that have been transformed with recombinant vectors carrying DNA inserts from a single species.

LIMS (Laboratory Information Management System)
Computer software that is used to track and monitor laboratory data. Data is entered and stored in a database.

Linkage
The co-inheritance of two or more genetic markers or physical traits. The closer together the genetic markers or genes are on a chromosome, the greater the probability that they will be inherited together or show linkage.

Linkage Disequilibrium (LD)
Greater co-occurrence of two genetic markers (on the same chromosome, as a haplotype) in a population than would be expected for independent markers. Usually, LD is generated when the markers are located close together on the same chromosome. When variants of two genetic loci are in strong LD, the variant seen at one locus are predictive of the variant found at the other on an individual chromosome.

Linked Genes (Linked Markers)
Genes and/or markers that are closely associated on a chromosome. This determination is usually by means of linkage analysis, but may also be inferred if the markers are in linkage disequilibrium.

Locus
The position of a SNP, gene or other feature on a chromosome.

Lysate
The contents released from a lysed cell.

Marker
Any genetic element (locus, allele, DNA sequence or chromosome feature) which can be readily detected by phenotype, cytological or molecular techniques, and used to follow a chromosome or chromosomal segment during genetic analysis.

Messenger RNA (mRNA)
The RNA molecule that serves as a template for protein synthesis.

Microarray
Sets of miniaturized chemical reaction areas that may be used to test DNA fragments, antibodies, or proteins.

Microsatellite DNA
Very short pieces of DNA that are repeated 2 to 5 times. Because of their typically high level of polymorphism, microsatellite loci are often used as genetic markers.

Mitochondria
Energy-transforming structures found in all cells. Each mitochondrion has a circular chromosome with a small number of genes on it. This chromosome resembles that of the bacteria-like ancestor of the mitochondria.

Mitochondrial DNA
DNA found in the mitochondria.

Multi-Factorial Disease
A disease that appears because of more than one factor, usually genetic and environmental.

Mutation
A change in the DNA sequence that occurs during the course of replication or DNA damage and repair.

Northern Blotting
Transfer of electrophoretically separated RNA molecules from a gel onto an absorbent sheet, which is then blocked to prevent nonspecific binding and immersed in a labeled probe that will hybridize to an RNA of interest to reveal its presence.

Nucleotide
A subunit or base of DNA or RNA made up of adenine (A), guanine (G), thymine (T) or cytosine (C) for DNA; A, G, uracil (U) or C for RNA, along with a phosphate molecule and a sugar molecule (deoxyribose in DNA and ribose in RNA). Nucleotides are linked together to form a DNA or RNA molecule.

Nucleus
The part of the cell that contains the autosomes and the X and Y chromosomes.

Oligonucleotide
A molecule usually composed of 25 or fewer nucleotides.

PAC (P1-Derived Artificial Chromosome)
One type of vector used to clone DNA fragments (100- to 300-kb insert size) in Escherichia coli cells. Based on bacteriophage P1 genome.

Phenotype
An observable trait of an organism resulting from the interplay of environment and genetics. In pharmacogenetics, variable efficacy and adverse reactions are phenotypes of interest.

Pharmacogenomics
The application of genomics to the study of human variability in drug response.

Plasmid
Autonomously replicating extra chromosomal rings of DNA present in monerans and some other organisms.

Polymerase
A multisubunit enzyme which plays a role in synthesizing new DNA strands using a DNA template by catalyzing the formation of phosphodiester bonds.

Polymerase Chain Reaction (PCR)
A method for amplifying specific DNA segments which exploits certain features of DNA replication; replication requires a primer and specificity is determined by the sequence and size of the primer. The method amplifies specific DNA segments by cycles of template denaturation; primer addition; primer annealing and replication using thermostable DNA polymerase. In addition to primers and DNA polymerase, PCR reactions must contain template DNA (the DNA to be amplified) and the DNA "building blocks", deoxynucleotide triphosphates (dNTPs, which include dATP, dTTP, dGTP, and dCTP).

Polymorphism
Differences in DNA sequences that occur naturally in a population. Single nucleotide substitutions, insertions and deletions of nucleotides and repetitive sequences (microsatellites) are all examples of a polymorphism. The position at which such a sequence difference is found is a polymorphic site.

Population Genetics
The study of variation in genes among a group of individuals.

Primer
A short sequence (of RNA or DNA) from which DNA replication can initiate. May be either a synthetic DNA or RNA or a length of RNA synthesized in vivo.

Probe
A single-stranded DNA molecule used in laboratory experiments to detect the presence of a complementary sequence among a mixture of other singled-stranded DNA molecules.

Promoter
An upstream portion of a gene responsible for its activation and deactivation.

Prospective Study
Clinical studies in which patients are recruited before the clinical outcome is known and are followed through the course of treatment.

Protein
A family of large natural chemicals in the body. Each is composed of amino acids in the order specified by the gene that encodes it.

Q-PCR (also known as Real Time PCR, Quantitative PCR, Real-time Quantitative PCR, or RTQ-PCR-- but not RT-PCR)
A method of simultaneous DNA quantification and amplification. DNA is specifically amplified by polymerase chain reaction (PCR). After each round of amplification, the DNA is quantified.

Recessive
The property of an allele whereby possessing either one or zero copies of the allele results in the same phenotype. Having two copies allows the allele's function to be seen. Contrast with dominant

Recombinant
Techniques of gene cloning. Recombinant DNA refers to the molecule formed by joining a DNA of interest to vector DNA.

Replication
DNA synthesis. The process of copying.

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

Retrospective Study
A clinical study in which patients are recruited after the clinical outcome is known. This type of study is particularly useful when examining rare occurrences, such as a dangerous reaction experienced by only a small percentage of patients being treated with a drug.

Reverse Transcription
The process of copying information found in RNA into DNA.

RFLP (Restriction Fragment Length Polymorphisms)
Variation in DNA fragment banding patterns of electrophoresed restriction digests of DNA from different individuals of a species. Often due to the presence of a restriction enzyme cleavage site at one place in the genome in one individual and the absence of that specific site in another individual.

RNA (Ribonucleic Acid)
A single-stranded nucleic acid containing the bases A, C, G and U and having an important role in protein synthesis and other chemical activities of the cell. There are several classes of RNA molecules, including messenger RNA, transfer RNA, ribosomal RNA, and other small RNAs, each serving a different function

RT PCR (Reverse Transcriptase Polymerase Chain Reaction)
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The cDNA is then amplified using standard PCR protocols.

Shotgun Technique
Cloning a large population of different DNA fragments, known to contain a fragment of interest, as a prelude to selecting or screening for that one particular clone containing the fragment of interest for intensive study.

Single Nucleotide Polymorphism (SNP)
A polymorphism where the alleles differ by the replacement of a single nucleotide in the DNA sequence. For most SNPs, only two of the four possible nucleotides (A, T, C, or G) are observed.

Southern Blotting
Transfer of electrophoretically separated fragments of DNA, after denaturation, from the gel to an absorbent sheet of material, such as nitrocellulose, to which the DNA binds. The sheet is immersed in a solution containing a labeled probe that will hybridize to fragment(s) of interest.

Subcloning
The process of transferring a cloned DNA fragment from one vector to another.

Template
In DNA replication each strand of the duplex acts as a template for the synthesis of a new double helix.

Transcription Profiling
A method of collecting and analyzing the genes that are expressed, usually in different backgrounds (normal vs. disease states). Transcriptional profiling is usually done using microarrays.

Transformation
The modification of a genome by the external application of DNA from a cell of different genotype.

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 vector’s capacity for self-replication; vectors introduce foreign DNA into host cells, where the DNA is replicated autonomously in large quantities. Examples are plasmids, cosmids, and yeast artificial chromosomes; vectors are often recombinant molecules containing DNA sequences from several sources.