Download Genomics Glossary - College of American Pathologists

Definition of Genomics at the
CAP and Glossary of Key Terms
Author(s): Gail Habegger Vance MD, FCAP, George Fiedler, Tim Bragg, David
Greenfeld, Jill Kaufman, PhD, Jodi Soriano, Nazneen Aziz, PhD, Fay
Shamanski, PhD, Bernadine Prygrosky, Jeff McNeal, Patricia Vasalos, Stanley
J. Robboy MD, FCAP, Karl V. Voelkerding MD, FCAP, Louis D. Wright Jr., MD,
FCAP, Debra G.B. Leonard MD, PhD, FCAP, Walter H. Henricks MD, FCAP,
Iris Schrijver MD, FCAP, Gregory J. Tsongalis, PhD
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Definition of Genomics at the CAP and Glossary of Key Terms
Genomics Definition for the CAP and Pathology
The genome is the complete set of DNA within a single cell of an organism.
Genomics – the study and application of recombinant DNA, mitochondrial DNA, pathogen
DNA/RNA, DNA sequencing methods, and bioinformatics to sequence, assemble, and
analyze the function and structure of genomes.
Genomics for the CAP - genomic medicine, molecular pathology, and clinical care based
on genomic information. This includes the application and utility of large-scale genomic
information management and data architecture in healthcare diagnostics in pursuit of
efficient and cost-effective patient care and health outcomes at the level of individuals,
institutions, populations, and communities. 1
Clinical Informatics - a discipline within informatics that we define as “the application of
information management in healthcare in pursuit of safe, efficient, effective, and costeffective patient care and health outcomes at the level of individuals, institutions,
2
populations, and communities.” The term informatics is broad with many similar, but
somewhat different, definitions. We chose the definition of informatics as the “science of
information management” for the purposes of this strategy.
1
Definition proposed by Gail Habegger Vance, MD, FCAP and CAP’s Genomics Strategy Workgroup –
endorsed by Advisory Group
2
Definition proposed by Andrew E. Horvath, MD, FCAP and Walter H. Henricks, MD, FCAP and CAP’s
Informatics Strategy Workgroup – endorsed by Advisory Group
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Definition of Genomics at the CAP and Glossary of Key Terms
Glossary of Key Terms and Phrases
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Allele:
Alternative form of a genetic locus; a single allele for each locus is inherited from
each parent (e.g., at a locus for eye color the allele might result in blue or brown
eyes).
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.
Bioinformatics:
The study of methods for storing, retrieving and analyzing biological data, such as
nucleic acid (DNA/RNA) and protein sequence, structure, function, pathways (neural
pathways included) and genetic interactions. It generates new knowledge that is
useful in such fields as drug design and development of new software tools to create
that knowledge. Bioinformatics also deals with algorithms, databases and information
systems, web technologies, artificial intelligence and soft computing, information and
computation theory, structural biology, software engineering, data mining, image
processing, modeling and simulation, discrete mathematics, control and system
theory, circuit theory, and statistics.
Complementary DNA (cDNA):
DNA that is synthesized in the laboratory from a messenger RNA template.
Chromosome:
The self-replicating genetic structure 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.
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Definition of Genomics at the CAP and Glossary of Key Terms
Cis:
Allele(s) on the same chromosome.
Codon:
The sequence of nucleotides, coded in triplets (codons) along the mRNA, that
determines the sequence of amino acids in protein synthesis. A gene's DNA
sequence can be used to predict the mRNA sequence, and the genetic code can in
turn be used to predict the amino acid sequence.
Copy number variant:
The gene copy number (also "copy number variants" or CNVs) is the number of
copies of a particular gene in the genotype of an individual.
Deoxyribonucleic acid (DNA):
An informational molecule encoding the genetic instructions used in the
development and functioning of all known living organisms and many viruses. Along
with RNA and proteins, DNA is one of the three major macromolecules that are
essential for all known forms of life. Genetic information is encoded as a sequence
of nucleotides (guanine, adenine, thymine, and cytosine) recorded using the letters
G, A, T, and C. Most DNA molecules are double-stranded helices, consisting of two
long polymers of simple units called nucleotides, molecules with backbones made of
alternating sugars (deoxyribose) and phosphate groups (related to phosphoric acid),
with the nucleobases (G, A, T, C) attached to the sugars. DNA is well-suited for
biological information storage, since the DNA backbone is resistant to cleavage and
the double-stranded structure provides the molecule with a built-in duplicate of the
encoded information.
Epigenetics:
Epigenetics is an emerging field of science that studies heritable changes caused by
the activation and deactivation of genes without any change in the underlying DNA
sequence of the organism. The word epigenetics is of Greek origin and literally
means over and above (epi) the genome.
Epigenome:
The term epigenome is derived from the Greek word epi which literally means
“above” the genome. The epigenome consists of chemical compounds that modify, or
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Definition of Genomics at the CAP and Glossary of Key Terms
mark, the genome in a way that tells it what to do, where to do it, and when to do it.
Different cells have different epigenetic marks. These epigenetic marks, which are
not part of the DNA itself, can be passed on from cell to cell as cells divide, and from
one generation to the next.
Epistasis:
Epistasis is a circumstance where the expression of one gene is affected by the
expression of one or more independently inherited genes. For example, if the
expression of gene #2 depends on the expression of gene #1, but gene #1 becomes
inactive, then the expression of gene #2 will not occur. In this example, gene #1 is
said to be epistatic to gene #2.
Exon:
The protein-coding DNA sequence of a gene.
Exome:
The part of the genome formed by exons, the coding portions of genes that are
expressed to provide the genetic blueprint used in the synthesis of proteins and other
functional gene products.
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).
Gene expression:
The process by which a gene's 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).
Genetic Marker:
A gene or other identifiable portion of DNA whose inheritance can be followed.
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Definition of Genomics at the CAP and Glossary of Key Terms
Genome:
The complete set of DNA within a single cell of an organism.
Genomics:
The study and application of recombinant DNA, DNA sequencing methods, and
bioinformatics to sequence, assemble, and analyze the function and structure of
genomes.
Genomic Medicine:
Medical practice driven by genomic information for the care of individual patients.
Genotype:
The genetic constitution of an organism, as distinguished from its physical
appearance.
Heterozygote:
An organism that has two different alleles at one or more loci on homologous
chromosomes.
Homozygote:
An organism that has two identical alleles of a gene.
Insertion:
A chromosome abnormality in which a piece of DNA is incorporated into a gene and
thereby disrupts the gene's normal function.
Karyogram:
A photomicrograph of an individual's chromosomes arranged in a standard format
showing the number, size, and shape of each chromosome type; used in lowresolution physical mapping to correlate gross chromosomal abnormalities with the
characteristics of specific diseases.
Microarray:
Sets of miniaturized chemical reaction areas that may also be used to test DNA
fragments, antibodies, or proteins all contained on a single platform.
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Definition of Genomics at the CAP and Glossary of Key Terms
Monogenic disorder:
A disorder caused by mutation of a single gene.
Multiplexing:
A laboratory approach that performs multiple sets of reactions in parallel
(simultaneously); greatly increasing speed and throughput.
Mutation:
Any heritable change in DNA sequence.
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.
Oligonucleotide:
A molecule usually composed of 25 or fewer nucleotides; used as a DNA synthesis
primer.
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.
Pharmacogenomics:
The study of the interaction of an individual's genetic makeup and response to a
drug.
Phenotype:
The physical characteristics of an organism or the presence of a disease that may or
may not be genetic.
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 one complementary to the (-) strand at the other end.
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Definition of Genomics at the CAP and Glossary of Key Terms
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.
Polymorphism:
Difference in DNA sequence among individuals that may underlie differences in
health. Genetic variations occurring in more than 1% of a population would be
considered useful polymorphisms for genetic linkage analysis.
Primer:
Short preexisting polynucleotide chain to which new deoxyribonucleotides can be
added by DNA polymerase.
Pseudogene:
A sequence of DNA similar to a gene but nonfunctional; probably the remnant of a
once-functional gene that accumulated mutations.
Recombinant DNA (rDNA):
DNA sequences that result from the use of laboratory methods (molecular cloning)
to bring together genetic material from multiple sources, creating sequences that
would not otherwise be found in biological organisms. Recombinant DNA is possible
because DNA molecules from all organisms share the same chemical structure; they
differ only in the sequence of nucleotides within that identical overall structure.
Consequently, when DNA from a foreign source is linked to host sequences that can
drive DNA replication and then introduced into a host organism, the foreign DNA is
replicated along with the host DNA.
Recessive gene:
A gene which will be expressed only if there are 2 identical copies or, for a male, if
one copy is present on the X chromosome.
Sequencing methods:
The processes and instrumentation for determining the precise order of nucleotides
within a DNA molecule. It includes any method or technology that is used to
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Definition of Genomics at the CAP and Glossary of Key Terms
determine the order of the four bases—adenine, guanine, cytosine, and thymine—in
a strand of DNA. These include chain termination methods such as Sanger
sequencing, de novo methods such as Shotgun sequencing and Bridge polymerase
chain reaction, and the Next Generation Sequencing methods such as single
molecule real time sequencing (SMRT), heliscope single molecule sequencing, DNA
nanoball sequencing, ion semiconductor sequencing, SOLiD sequencing by ligation,
Illumina sequencing by reversible dye-terminators, pyrosequencing, and Polony
sequencing.
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.
Single-gene disorder:
Hereditary disorder caused by a mutant allele of a single gene (e.g., Duchenne
muscular dystrophy, retinoblastoma, sickle cell disease).
Single Nucleotide Polymorphism:
Single nucleotide polymorphisms (SNPs) are a type of polymorphism involving
variation of a single base pair. Scientists are studying how single nucleotide
polymorphisms, or SNPs (pronounced "snips"), in the human genome correlate with
disease, drug response, and other phenotypes.
Somatic cell genetic mutation:
A change in the genetic structure that is neither inherited nor passed to offspring.
Also called acquired mutations.
Suppressor gene:
A gene that can suppress the action of another gene.
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Definition of Genomics at the CAP and Glossary of Key Terms
Tandem repeat sequences:
Multiple copies of the same base sequence on a chromosome; used as markers in
physical mapping.
Trans:
Allele on the other chromosome homolog.
Transcription:
The synthesis of an RNA copy from a sequence of DNA (a gene); the first step in
gene expression.
Transcriptome:
The full complement of activated genes, mRNAs, or transcripts in a particular tissue
at a particular time.
Translation:
The process in which the genetic code carried by mRNA directs the synthesis of
proteins from amino acids.
Translocation:
A mutation in which a large segment of one chromosome breaks off and attaches to
another chromosome.
Variant:
An alteration in the normal sequence of a gene, the significance of which is often
unclear until further study of the genotype and corresponding phenotype occurs in a
sufficiently large population. Complete gene sequencing often identifies numerous
allelic variants (sometimes hundreds) for a given gene.
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