Introduction to Pharmacogenetics and Genomics

These flashcards cover the fundamental vocabulary and concepts of pharmacogenetics and pharmacomics, including inheritance patterns, types of genetic variations, and their clinical implications.

Pharmacogenetics

The study of the genetic basis of variation in drug response, often focusing on a specific gene that affects a transporter, ion channel, or receptor.

Pharmacogenomics

The study of how more than one gene influences the outcome of how a human being responds to drugs.

Genotype

The genetic makeup of an individual, inherited from their parents, which partly dictates drug response alongside environmental factors.

Phenotype

The observable response of an individual to a drug, such as therapeutic effect or toxicity, resulting from the interaction of genotype and the environment.

Promoter

A segment of DNA located before the start of a gene that controls how much of the gene is being expressed or shut down.

Exons

The coding sequences of a gene that are joined together to form the mature messenger RNA ($mRNA$).

Introns

The non-coding parts of a gene located between exons that do not code for proteins.

Allele

A different version of a gene resulting from a mutation, which allows for genetic diversity within a population.

Autosomal Dominant

An inheritance pattern where inheriting only one variant allele is sufficient to produce an altered drug response.

Autosomal Recessive

An inheritance pattern where an individual must inherit two non-functional alleles to show an altered drug response.

Polymorphism

Any variation in the DNA that is present in more than $1\%$ of the population.

SNP (Single Nucleotide Polymorphism)

The most common type of polymorphism involving a change in a single DNA base pair (e.g., $A$ to $G$), occurring every $100$ to $1,000$ base pairs.

Indels

Small sections of DNA that are either added to or removed from the genome; they are less common than SNPs and rarely found in coding regions.

Copy Number Variations

Large sections of DNA or entire chromosomes that are duplicated or deleted, such as in Trisomy $21$.

Non-synonymous change

A variant in the coding region that results in a change in the amino acid sequence, potentially altering protein folding and function.

Synonymous change

A base pair substitution in the coding region that does not change the amino acid being coded, though it may affect $mRNA$ stability.

Nonsense Mutation

A genetic change that prematurely results in a stop codon, leading to the production of a truncated and non-functional protein.

Haplotype

A group of genetic variants that are inherited together on a single chromosome.

Linkage Disequilibrium

A condition where specific genetic variants occur together within a population more frequently than would be expected by chance.

Cosmopolitan Polymorphisms

Genetic variants found across all populations that are likely older and acquired during human evolution.

Population-specific Polymorphisms

Genetic variants found only in certain ethnic groups or geographical locations due to adaptation or isolation.

Poor Metabolizer

An individual with little to no enzyme activity (e.g., $CYP2D6$ deficiency) who breaks down drugs slowly, leading to high blood levels and potential toxicity.

Ultra-rapid Metabolizer

An individual who breaks down a drug very quickly, potentially clearing the drug from the system before it can provide therapeutic benefit.

G6PD deficiency

A monogenic X-linked disorder that makes red blood cells susceptible to oxidative damage, specifically causing hemolytic anemia when treated with drugs like primaquine.

Somatic Mutations

Mutations acquired over time that exist only in specific cells, such as cancer cells, rather than throughout the entire body.

Modifying Polymorphisms

Variants that do not directly affect drug action but increase an individual's underlying vulnerability to specific adverse effects, such as thrombosis or arrhythmia.