biosimilar: term for generic biologics because initial product cannot be replicated exactly

next generation sequencing (NGS): approach to determine the sequence of entire human genomes

deoxyribonucleic acid (DNA): molecule that contains biological instructions that make each species unique

genes: DNA that contains instructions to make proteins and functional RNAs

mRNA: RNA that is translated into proteins

gene variant: permanent change in the DNA sequence of a gene

silent gene variant: change DNA and mRNA, but not protein

missense gene variant: a nucleotide change the results in a protein change

nonsense gene variant: inserts a stop codon that terminates translation

insertion gene variant: adds one or more nucleotides to the gene

deletion gene variant: deletes or more nucleotides from the gene

frameshift: when the gene shifts out of its normal three-frame register

indel: when insertions and deletions occur at the same time

duplication: when a stretch of nucleotides is copied and repeated next to the original sequence

repeat expansion: multiple duplications of the same sequence

copy number variation (CNV): some genomes contain fewer or many more than two genes

aneuploidy: a change in chromosome number from 46

translocation: when part of a chromosome breaks off and attaches to another chromosome

hereditary variants: variants passed from parent to child

non-inherited variants: variants that occur during a person’s lifetime

mosaicism: cells with varying genetic makeup in the body

autosomal dominant inheritance: one altered copy is sufficient to cause a disorder

autosomal recessive inheritance: variants in both copies are required for the disorder to manifest

X-linked dominant inheritance: caused by gene variants on the X chromosome, males and females who inherit an X with the variant will show the disorder

X-linked recessive inheritance: for females: need variants on both X-chromosomes to show disorder; only need one variant (only one X chromosome)

Y-linked inheritance: disease associated variant is found on the Y chromosome

codominant inheritance: two different variants of the same gene are expressed that make different proteins

alleles: different variants of the same gene

mitochondrial inheritance: variant occurs in the mitochondrial DNA

monogenic disease: genetic diseases associated with one gene, or one position on the chromosome

locus: a gene or position on the chromosome

phenotype: observable characteristic of a gene variant

gain-of-function: toxic gene variant that causes disease

loss-of-function: variant reduces protein function, leading to disease

heterozygous: individual has two different alleles of a gene

proteosome: protein degradation machinery in the cell, often degrades protein aggregates

exons: protein encoding parts of genes/mRNAs

introns: non-coding parts of an mRNA that are removed by splicing

alternative splicing: results in different protein products from the same gene

polygenic disease=complex/multifactoral disorders: conditions/diseases that are caused by variants in multiple genes

modifier genes: gene variants can interact and change the disease phenotype

penetrance: % of individuals with a given genotype that express the phenotype

expressivity: degree to which an individual with a given genotype expresses a phenotype

hypertension: high blood pressure

primary (essential) hypertension: no identifiable cause of high blood pressure

secondary hypertension: caused by an underlying condition

polygenic risk scores: use of statistics to calculate a person or population's risk of genetic disease based on multiple genes; attempt to determine the relative risk for complex diseases

dizygotic twins: fraternal twins from two separate fertilization events

monozygotic twins: identical twins with the same initial genome sequence

Genome-wide Association Studies (GWAS): scan for disease markers across entire genomes

single nucleotide polymorphism (SNP): a single nucleotide variant in DNA

whole exome sequencing: selective sequencing of all exons in the genome

Manhattan Plot: plot showing the statistical significance of genes from a GWAS study

gene expression: the amount of RNA or protein produced by a gene

promoter: DNA sequence that initiates transcription/gene expression

enhancers: increase gene expression

silencers: reduce gene expression

insulators: block the effect of enhancers at adjacent genes

epigenetics: modification of DNA that affects gene expression

personalized genomics: using genomics to define or predict disease based on individual's DNA sequence or other genome-scale biomarkers

pharmacogenomics: how a person's genetic background affects drug response

biomarkers: DNA/RNA/protein features that correlate with disease risk or therapy efficacy

microsatellites: short DNA repeats

microsatellite instability (MSI): small deletions and insertions in microsatellite DNA

DNA mismatch repair (MMR): proteins that correct replication mistakes made by DNA polymerase

DNA mismatch repair deficiency (dMMR): a defective MMR pathway that leads to accumulation of mutations

neoantigens: new proteins found on the outside of tumor cells due to DNA mutations

pharmacogenes: genes with variants that affect drug pharmacokinetics or pharmacodynamics

pharmacokinetic genes: genes that affect pharmacokinetics of drugs (metabolism)

pharmacodynamic genes: genes that affect pharmacodynamics of drugs (mode of action)

poor, intermediate, normal, and ultrarapid metabolizers: a continuum of individuals with different kinetics of drug metabolism

structural variants: large-scale deletions or duplications affect drug metabolism

null allele: gene variant with no activity, results in less drug metabolism for pharmacokinetic genes