Pharmacogenetics
Study of the relationship between variations in a single gene and variability in drug disposition, response, and toxicity
Pharmacogenomics (PGx)
Encompasses all the genes in a genome that may determine an individual's drug response; study of the relationship between variations in a large collection of genes (up to the whole genome) and variability in drug disposition, response, and toxicity
Gene
Unit of heredity; a section of DNA sequence encoding a biological component, usually a protein
Wild-type
Most common or reference allele that is a functional gene version
Polymorphic variants (literally "multiple forms")
Alleles with sequence deviations from the "wild-type" gene/allele
Allele
Term most often used to describe variable forms of the same gene and that cover the same trait (like 'flavors' of a trait)
Genetic Locus (plural loci)
Refers to the specific location of a particular segment of DNA, i.e., on which chromosome and where on that chromosome does a segment reside. A fixed location on a strand of DNA where a gene or one of its alleles is located
Genome
An organism's complete set of DNA, including all of its genes (and alleles), regulatory elements, and other nucleotide sequences
Dominant
The allele of a gene that masks or suppresses the expression of an alternate allele; the trait appears in the heterozygous condition
Recessive
An allele that is masked by a dominant allele; does not appear in the heterozygous condition, only in the homozygous condition
Genotype
The genetic makeup of an organism
Phenotype
The physical appearance of an organism or a measurable/observable characteristic (genotype + environment)
Genetic homogeneity
For a disease, a single polymorphism (mutation) only causes that condition, i.e., all affected individuals have the same mutation in the same gene
Genetic Heterogeneity
Different mutations cause an identical, or very similar, phenotype
Allelic heterogeneity
Different mutations within the same locus producing the same condition
Locus heterogeneity
Mutations at completely different loci producing the same phenotype
Linkage Disequilibrium (LD)
Non-random association of alleles at different loci on the same chromosome
The phenomenon by which the presence of one allele on a chromosome suggests a high probability that a particular allele will be present at a neighboring site on the same chromosome
Promoter
Region of DNA that initiates transcription of a particular gene. It contains DNA sequence that allows RNA polymerase and other transcription initiation factors to bind
5' Untranslated Region (5' UTR)
Region of a gene directly upstream from the start codon (i.e., before the start codon). It is also known as a leader sequence
Contains regulatory elements which play a role in gene expression
3' Untranslated Region (3' UTR)
Region of gene directly downstream from the termination codon (i.e., after the termination codon). It is also known as the trailer sequence
Contains regulatory regions that influence post-transcriptional gene expression
Exons
Portion of a gene that codes for amino acids. Sequence is retained in the mature messenger RNA (mRNA)
Codon
3 nucleotides that code for an amino acid
Introns
Portion of a gene that does not code for an amino acid. Intervening sequence that is removed during the mRNA splicing process
Genetic variants occur more commonly in non-coding regions than coding regions
Intergenic regions
Stretch of DNA sequences located between genes
Can contain regulatory information
Single nucleotide polymorphism (SNP)
DNA sequence variation where a single nucleotide is changed to another at a particular position within a genome
Silent Sequence Change (Synonymous SNP)
Changes that do not alter the encoded amino acid
Missense Mutation (Nonsynonymous SNP)
Changes to a codon for another amino acid (can be harmful mutation or neutral variant)
Nonsense Mutation (Nonsynonymous SNP)
Change from an amino acid codon to a stop codon, producing a shortened protein
Frameshift Mutation
Insertion or deletion of base pairs, producing a stop codon downstream and (usually) shortened protein
Haplotype
A set of closely linked alleles that are located on one chromosome and inherited together as a unit or "block." Also describes all SNPs on a chromosome, which are statistically linked with each other
Genotyping
Process used to determine the two alleles a person has at a particular DNA location
Allele discrimination
Process used to differentiate between wild-type and variant alleles
Allele detection
Process used to capture the information generated from the allele discrimination reaction
Polymerase Chain Reaction (PCR)
Method used to amplify a small segment of DNA, thereby generating millions of copies of that particular DNA sequence
Tag-SNP
Representative SNP in a region of the genome with high linkage that represents a group of SNPs in a haplotype block
Insertion or deletion (Indel)
Insertion or deletion of a single DNA base or multiple consecutive nucleotides from the DNA sequence
Variable number of tandem repeats (VNTR)
A sequence of nucleotides is repeated a variable number of times
Copy Number Variations (CNVs)
Gain (duplication) or loss (deletion) of large regions of DNA sequence
Splice-Site Variants
A genetic alteration in the DNA sequence that occurs at the boundary of an exon and an intron (splice site). This change can disrupt RNA splicing resulting in the loss of exons or the inclusion of introns and an altered protein-coding sequence
Variant in promoter or 5' UTR
May alter transcription factor binding and increase or decrease gene transcription
Variant in an exon
May change a codon sequence, resulting in a different amino acid or a premature stop codon; may have no effect
Variant in an intron
Often has no consequence. May have consequences if they are linked to other variants in the gene
Variant in an intron-exon splice junction
May alter the site of splicing and result in a transcript that lacks exons or contains pieces of introns
Variant in the 3' UTR
May alter mRNA stability, structure, or degradation