434 Peters Defs

• 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

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